John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

A blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.


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Gene delivery potential of PLA-PEG-Mal points to potential to use block polymers for mRNA vaccines

Tuesday, July 27, 2021, 12:08 PM ET

Current strategies primarily use lipid nanoparticles and liposomes for delivery of mRNA for vaccines such as the Pfizer and Moderna vaccines against Covid. The potential for delivery of genetic material has proven itself to be a powerful tool. Recent research has indicated the potential for gene delivery by PLA-PEG-Mal type polymeric particles as a potential therapy for irritable bowel disease. This points to the potential to use this class of polymers for delivery of mRNA and other genes as part of vaccination and other applications. Find these and other polymers at www.polyscitech.com

Verma, Priyanka, Aasheesh Srivastava, Chittur V. Srikanth, and Avinash Bajaj. "Nanoparticle-mediated gene therapy strategies for mitigating inflammatory bowel disease." Biomaterials science 9, no. 5 (2021): 1481-1502.https://pubs.rsc.org/en/content/articlehtml/2020/bm/d0bm01359e


Abstract: Inflammatory bowel disease (IBD) is an autoimmune disorder of the gastrointestinal tract (GIT) where Ulcerative Colitis (UC) displays localized inflammation in the colon, and Crohn's Disease (CD) affects the entire GIT. Failure of current therapies and associated side-effects bring forth serious social, economic, and health challenges. The gut epithelium provides the best target for gene therapy delivery vehicles to combat IBD. Gene therapy involving the use of nucleic acid (NA) therapeutics faces major challenges due to the hydrophilic, negative-charge, and degradable nature of NAs. Recent success in the engineering of biomaterials for gene therapy and their emergence in clinical trials for various diseases is an inspiration for scientists to develop gene therapy vehicles that can be easily targeted to the desired tissues for IBD. Advances in nanotechnology have enabled the formulations of numerous nanoparticles for NA delivery to mitigate IBD that still faces challenges of stability in the GIT, poor therapeutic efficacy, and targetability. This review presents the challenges of gene therapeutics, gastrointestinal barriers, and recent advances in the engineering of nanoparticles for IBD treatment along with future directions for successful translation of nanoparticle-mediated gene therapeutics in clinics.

Nuplon Heat-Curable Resin Free Samples Available For Testing and Applications Research

Tuesday, July 27, 2021, 11:37 AM ET

In an effort to aid in combating plastic contamination of waterways and landfills, Akina, Inc. has recently developed a biodegradable, self-crosslinking resin. Intellectual property protection on the background technology for Nuplon was filed by Akina, Inc. with a priority date of June 25, 2020 and patent protection is currently pending under filing number US 2021070743. Akina, Inc. is actively seeking a partner interested in end-product applications for the Nuplon material. To that end, we’re putting Nuplon in the hands of the smartest people we know.


Starting from July, 2021, samples of “pour-and-cure” heat-curable Nuplon resin are free to request from the website (https://akinainc.com/polyscitech/products/NuPlon/index.php) with only cost being shipping charges for USPS shipping. Additionally, on any order simply type “Nuplon” into the “Special Instructions” section to receive your free sample.

-Nuplon Details-

Description: Prepolymer is a set of low molecular weight oligomeric esters comprised of varying lengths of lactides and other esters combined with multifunctional alcohols and multifunctional acids. Prepolymer is a viscous liquid (Brookfield spindle, 20 ⁰C, 1000 – 3000 cP). To cure: Pour solution into desired shape of mold or onto components. Nuplon has proven to be strongly adhesive so use of either PTFE, silicone rubber, or molds coated with mold-release aid is suggested to prevent adhesion. Heat in an oven at 150 – 170 ⁰C overnight (16-24 hours) to cure. Afterwards, demold product and cut/machine to form the final shape. Adhesion: Nuplon prepolymer has strong adhesive properties and may be used to attach two components together. For this simply clamp the pieces together with the Nuplon between them and cure as described above. Post-Cure Performance: Final product is optically clear, hard plastic. Mechanical: Elastic Modulus (0.1 – 1% strain): 4.8 + 1.6 MPa, Tensile Strength: 31.0 + 19.2 MPa, Extensibility: 5.3 + 1.6 % strain, Temperature stable up to 350 ⁰C when dry. Degradation: Under normal exposure to humidity in an indoor location (20 – 25C, 30 - 80% RH) product softens after about six months and degrades after about 1-2 years forming into a soft, gel. When hydrated, will quickly become flexible after a day or two and fully degrade to non-toxic products after 2-3 months in water. For other applications and technical information visit http://www.nuplon.com/tech

PLGA from PolySciTech used in development of probiotic intestinal delivery

Tuesday, July 27, 2021, 11:37 AM ET

Humans require certain forms of bacteria in their intestine in order to provide for digestion as well as prevention of the growth of pathological bacterial. Despite the plethora of consumer products advertising probiotic contents these, in general, are poorly effective at establishing probiotic colonies in the intestines due to acidic degradation in the stomach. Recently, researchers at Pusan National University, The University of Arizona, Pohang University of Science and Technology, and Korea University used PLGA (AP121) from PolySciTech (www.polyscitech.com) as part of development of a delivery system for probiotics. This holds promise to assist people who have digestive disorders. Read more: Kim, Jihyun, Shwe Phyu Hlaing, Juho Lee, Aruzhan Saparbayeva, Sangsik Kim, Dong Soo Hwang, Eun Hee Lee et al. "Exfoliated bentonite/alginate nanocomposite hydrogel enhances intestinal delivery of probiotics by resistance to gastric pH and on-demand disintegration." Carbohydrate Polymers (2021): 118462. https://www.sciencedirect.com/science/article/pii/S0144861721008493 “Highlights: LGG was encapsulated in exfoliated bentonite/alginate nanocomposite hydrogels. Improved hydrogel pore size dramatically enhanced LGG survival at gastric pH. Complete intestinal release of LGG was observed after hydrogel disintegration. Fecal recovery of bentonite/alginate LGG was 6-fold greater than of alginate LGG. Abstract: In this study, we developed Lactobacillus rhamnosus GG (LGG)-encapsulating exfoliated bentonite/alginate nanocomposite hydrogels for protecting probiotics by delaying gastric fluid penetration into the nanocomposite and their on-demand release in the intestine. The pore size of the bentonite/alginate nanocomposite hydrogels (BA15) was two-fold smaller than that of alginate hydrogel (BA00). Following gastric pH challenge, the survival of LGG in BA15 decreased by only 1.43 log CFU/g as compared to the 6.25 log CFU/g decrease in alginate (BA00). Further, the internal pH of BA15 decreased more gradually than that of BA00. After oral administration in mice, BA15 maintained shape integrity during gastric passage, followed by appropriate disintegration within the target intestinal area. Additionally, a fecal recovery experiment in mice showed that the viable counts of LGG in BA15 were six-fold higher than those in BA00. The findings suggest the exfoliated bentonite/alginate nanocomposite hydrogel as a promising platform for intestinal delivery of probiotics. Keywords: probiotics alginate bentonite nanocomposite gastric pH resistance intestinal delivery”

PLGA-PEG-Maleimide from PolySciTech used in the development of gefitinib loaded/p28 targeted nanoparticles for lung cancer treatment

Tuesday, July 27, 2021, 11:36 AM ET

Delivery of medicinal molecules to cancer cells is difficult based on the ability of the medicine to specifically target towards the tumor site as well as to cross into the cancer cell. This can be improved by attaching targeting ligands to the nanoparticles to improve their uptake. Recently, researchers at University of Lisbon, University of Porto, and CESPU-Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to develop targeted nanoparticles for delivery of gefitinib to lung cancer. This research holds promise to improve treatment options for this fatal disease. Read more: Garizo, Ana Rita, Flávia Castro, Cláudia Martins, Andreia Almeida, Tiago P. Dias, Fábio Fernardes, Cristina C. Barrias, Nuno Bernardes, Arsénio M. Fialho, and Bruno Sarmento. "p28-functionalized PLGA nanoparticles loaded with gefitinib reduce tumor burden and metastases formation on lung cancer." Journal of Controlled Release (2021). https://www.sciencedirect.com/science/article/pii/S0168365921003783

“Abstract: Lung cancer is still the main cause of cancer-related deaths worldwide. Its treatment generally includes surgical resection, immunotherapy, radiotherapy, and chemo-targeted therapies such as the application of tyrosine kinase inhibitors. Gefitinib (GEF) is one of them, but its poor solubility in gastric fluids weakens its bioavailability and therapeutic activity. In addition, like all other chemotherapy treatments, GEF administration can cause damage to healthy tissues. Therefore, the development of novel GEF delivery systems to increase its bioavailability and distribution in tumor site is highly demanded. Herein, an innovative strategy for GEF delivery, by functionalizing PLGA nanoparticles with p28 (p28-NPs), a cell-penetrating peptide derived from the bacterial protein azurin, was developed. Our data indicated that p28 potentiates the selective interaction of these nanosystems with A549 lung cancer cells (active targeting). Further p28-NPs delivering GEF (p28-NPs-GEF) were able to selectively reduce the metabolic activity of A549 cells, while no impact was observed in non-tumor cells (16HBE14o-). In vivo studies using A549 subcutaneous xenograft showed that p28-NPs-GEF reduced A549 primary tumor burden and lung metastases formation. Overall, the design of a p28-functionalized delivery nanosystem to effectively penetrate the membranes of cancer cells while deliver GEF could provide a new strategy to improve lung cancer therapy. Keywords Azurin Cell penetrating peptide EGFR inhibitor Nanosized drug delivery system Active targeting Cancer therapy”

PLCL from PolySciTech used in development of 3D Cell-Laden microstructures for tissue engineering applications

Tuesday, July 20, 2021, 4:56 PM ET

Tissue regeneration and tissue engineering applies to processes whereby diseased or damaged tissue is either encouraged to heal or temporarily replaced with a construct which provides for healing. Such a technology can be applied to instances of traumatic damage where normally grafting would be necessary without requiring collection of graft tissue and the limitations associated with this. Recently, researchers at State University of New York at Buffalo used PLCL (AP034, AP074, AP067, and AP142) from PolySciTech (www.polyscitech.com) to create a 3D cell-laden structure by micromachining/manipulation of a cell-seeded 2D surface. This research holds promise to provide for tissue-engineering constructs to aid in healing of damaged tissue. Read More: Chen, Zhaowei, Nanditha Anandakrishnan, Ying Xu, and Ruogang Zhao. "Compressive Buckling Fabrication of 3D Cell‐Laden Microstructures." Advanced Science (2021): 2101027. https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202101027

“Abstract: Tissue architecture is a prerequisite for its biological functions. Recapitulating the three-dimensional (3D) tissue structure represents one of the biggest challenges in tissue engineering. Two-dimensional (2D) tissue fabrication methods are currently in the main stage for tissue engineering and disease modeling. However, due to their planar nature, the created models only represent very limited out-of-plane tissue structure. Here compressive buckling principle is harnessed to create 3D biomimetic cell-laden microstructures from microfabricated planar patterns. This method allows out-of-plane delivery of cells and extracellular matrix patterns with high spatial precision. As a proof of principle, a variety of polymeric 3D miniature structures including a box, an octopus, a pyramid, and continuous waves are fabricated. A mineralized bone tissue model with spatially distributed cell-laden lacunae structures is fabricated to demonstrate the fabrication power of the method. It is expected that this novel approach will help to significantly expand the utility of the established 2D fabrication techniques for 3D tissue fabrication. Given the widespread of 2D fabrication methods in biomedical research and the high demand for biomimetic 3D structures, this method is expected to bridge the gap between 2D and 3D tissue fabrication and open up new possibilities in tissue engineering and regenerative medicine.”

PLA from PolySciTech used in development of mussel inspired bio-adhesives

Tuesday, July 20, 2021, 4:55 PM ET

Adhesives are typically not environmentally friendly or biocompatible as they are manufactured of synthetic chemicals which do not provide for good interactions with cells. Recently, researchers at Purdue University used PLA (AP138) from PolySciTech (www.polyscitech.com) to create catechol modified PLA for adhesives usage and tested these for their interactions with cells. This holds promise to provide for either a bioadhesive or tissue engineering construct. Read more: Hollingshead, Sydney, Heather Siebert, Jonathan J. Wilker, and Julie C. Liu. "Cytocompatibility of a mussel‐inspired poly (lactic acid)‐based adhesive." Journal of Biomedical Materials Research Part A (2021). https://onlinelibrary.wiley.com/doi/abs/10.1002/jbm.a.37264

“Abstract: Incorporating catechols into polymers can provide strong adhesion even in moist environments, and these polymers show promise for use in several biomedical applications. Surgical adhesives must have strong bonds, be biocompatible, and function in a moist environment. Poly(lactic acid) (PLA) has a long history as a biocompatible material for hard tissue device fixation. By combining these concepts, catechol-containing poly(lactic acid) (cPLA) polymers are created that are strongly adhesive and degrade in physiological environments. Here, we evaluated the cytocompatibility of cPLA with iron(III) or periodate (IO4−) cross-linkers. Fibroblasts cultured in cPLA leachate or on cPLA films generally had slower growth and lower metabolism compared with PLA controls but no differences in viability. These results demonstrated that cPLA was not cytotoxic but that including catechols reduced cell health. When cPLA was cross-linked with periodate, cells generally had reduced metabolism, slower cell growth, and poor actin fiber formation compared with PLA. These results are attributed to the cytotoxicity of periodate since cells cultured with periodate leachate had extremely low viability. Cells grown on the films of iron-cross-linked cPLA generally had high viability and metabolism but slower proliferation than PLA controls. These results indicate that the cPLA and iron-cross-linked cPLA systems are promising materials for biomedical adhesive applications.”

PEG-PEI from PolySciTech used in development of Blood-Brain-Barrier crossing nanoparticles for gene therapy

Monday, July 19, 2021, 1:43 PM ET

Many central-nervous related diseases (Parkinson’s, Alzheimer’s, ALS, etc.) are difficult to treat due in part due to the design of the body which prevents many molecules from crossing over into the brain tissue from the blood-stream. Although the Blood-Brain-Barrier (BBB) is a necessary component to human survival as it protects the brain from potentially damaging chemicals it makes treating CNS diseases difficult. Recently, researchers at Tokyo University and Teikyo University (Japan) used PEG-PEI (AK086) from PolySciTech (www.polyscitech.com) to create gene-loaded nanoparticles for crossing the BBB. This research holds promise to improve therapy options against a range of neural diseases in the future. Read more: Endo-Takahashi, Yoko, Ryo Kurokawa, Kanako Sato, Nao Takizawa, Fumihiko Katagiri, Nobuhito Hamano, Ryo Suzuki et al. "Ternary Complexes of pDNA, Neuron-Binding Peptide, and PEGylated Polyethyleneimine for Brain Delivery with Nano-Bubbles and Ultrasound." Pharmaceutics 13, no. 7 (2021): 1003. https://www.mdpi.com/1999-4923/13/7/1003

“Abstract: In brain-targeted delivery, the transport of drugs or genes across the blood−brain barrier (BBB) is a major obstacle. Recent reports found that focused ultrasound (FUS) with microbubbles enables transient BBB opening and improvement of drug or gene delivery. We previously developed nano-sized bubbles (NBs), which were prepared based on polyethylene glycol (PEG)-modified liposomes containing echo-contrast gas, and showed that our NBs with FUS could also induce BBB opening. The aim of this study was to enhance the efficiency of delivery of pDNA into neuronal cells following transportation across the BBB using neuron-binding peptides. This study used the RVG-R9 peptide, which is a chimeric peptide synthesized by peptides derived from rabies virus glycoprotein and nonamer arginine residues. The RVG peptide is known to interact specifically with the nicotinic acetylcholine receptor in neuronal cells. To enhance the stability of the RVG-R9/pDNA complex in vivo, PEGylated polyethyleneimine (PEG-PEI) was also used. The ternary complexes composed of RVG-R9, PEG-PEI, and pDNA could interact with mouse neuroblastoma cells and deliver pDNA into the cells. Furthermore, for the in vivo experiments using NBs and FUS, gene expression was observed in the FUS-exposed brain hemispheres. These results suggest that this systemic gene delivery system could be useful for gene delivery across the BBB. Keywords: nanobubble; ultrasound; brain; gene delivery”

PLGA from PolySciTech used in development of nitric-oxide delivery system for cancer treatment

Wednesday, July 7, 2021, 3:04 PM ET

Nitric oxide works well as a local anticancer agent due to its low off-target side effect. For this to work, however, the nitric oxide must be delivered very precisely to the cancer cells. Recently, researchers at Pusan National University (Korea) used PLGA (AP037) from PolySciTech (www.polyscitech.com) to create nitric-oxide releasing nanoparticles for tumor treatment. This research holds promise to provide improved treatments for cancer. Read more: Lee, Juho, Shwe Phyu Hlaing, Nurhasni Hasan, Dongmin Kwak, Hyunwoo Kim, Jiafu Cao, In-Soo Yoon, Hwayoung Yun, Yunjin Jung, and Jin-Wook Yoo. "Tumor-Penetrable Nitric Oxide-Releasing Nanoparticles Potentiate Local Antimelanoma Therapy." ACS Applied Materials & Interfaces (2021). https://pubs.acs.org/doi/abs/10.1021/acsami.1c07407

“Abstract: Although nitric oxide (NO) has been emerging as a novel local anticancer agent because of its potent cytotoxic effects and lack of off-target side effects, its clinical applications remain a challenge because of the short effective diffusion distance of NO that limits its anticancer activity. In this study, we synthesized albumin-coated poly(lactic-co-glycolic acid) (PLGA)-conjugated linear polyethylenimine diazeniumdiolate (LP/NO) nanoparticles (Alb-PLP/NO NPs) that possess tumor-penetrating and NO-releasing properties for an effective local treatment of melanoma. Sufficient NO-loading and prolonged NO-releasing characteristics of Alb-PLP/NO NPs were acquired through PLGA-conjugated LP/NO copolymer (PLP/NO) synthesis, followed by nanoparticle fabrication. In addition, tumor penetration ability was rendered by the electrostatic adsorption of the albumin on the surface of the nanoparticles. The Alb-PLP/NO NPs showed enhanced intracellular NO delivery efficiency and cytotoxicity to B16F10 murine melanoma cells. In B16F10-tumor-bearing mice, the Alb-PLP/NO NPs showed improved extracellular matrix penetration and spatial distribution in the tumor tissue after intratumoral injection, resulting in enhanced antitumor activity. Taken together, the results suggest that Alb-PLP/NO NPs represent a promising new modality for the local treatment of melanoma.”

PEG-PLGA/PLGA from PolySciTech used in development of novel microfluidic-based nanoparticle generation method

Monday, June 21, 2021, 2:49 PM ET

Nanoparticles are typically generated by precipitation of hydrophobic polymers into an aqeous emulsion in which the polymer particles form inside the emulsified droplets of organic solvent in the emulsion mix. The way in which this emulsion is achieved can vary widely from simply rapid agitation of water-surfactant mixtures in an open-top container to precisely controlled microfluidic systems for generation of very uniform particles. Recently, researchers at Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology (Spain), and Eindhoven University of Technology (Netherlands) used PLGA (AP082) and PEG-PLGA (AK102) from PolySciTech (www.polyscitech.com) to research microfluidic generation of block-copolymer based nanoparticles. This research holds promise to improve the development of drug-loaded nanoparticles for treating a wide array of disease states including cancer. Read more: Mares, Adrianna Glinkowska, Gaia Pacassoni, Josep Samitier Marti, Silvia Pujals, and Lorenzo Albertazzi. "Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology." PloS one 16, no. 6 (2021): e0251821. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251821

“Abstract: Amphiphilic block co-polymer nanoparticles are interesting candidates for drug delivery as a result of their unique properties such as the size, modularity, biocompatibility and drug loading capacity. They can be rapidly formulated in a nanoprecipitation process based on self-assembly, resulting in kinetically locked nanostructures. The control over this step allows us to obtain nanoparticles with tailor-made properties without modification of the co-polymer building blocks. Furthermore, a reproducible and controlled formulation supports better predictability of a batch effectiveness in preclinical tests. Herein, we compared the formulation of PLGA-PEG nanoparticles using the typical manual bulk mixing and a microfluidic chip-assisted nanoprecipitation. The particle size tunability and controllability in a hydrodynamic flow focusing device was demonstrated to be greater than in the manual dropwise addition method. We also analyzed particle size and encapsulation of fluorescent compounds, using the common bulk analysis and advanced microscopy techniques: Transmission Electron Microscopy and Total Internal Reflection Microscopy, to reveal the heterogeneities occurred in the formulated nanoparticles. Finally, we performed in vitro evaluation of obtained NPs using MCF-7 cell line. Our results show how the microfluidic formulation improves the fine control over the resulting nanoparticles, without compromising any appealing property of PLGA nanoparticle. The combination of microfluidic formulation with advanced analysis methods, looking at the single particle level, can improve the understanding of the NP properties, heterogeneities and performance.”

PEG-PLGA from PolySciTech used in quantitative analysis of fluorescent dye performance with varying nanoparticle loads.

Monday, June 21, 2021, 2:48 PM ET

Due to their chemical structure, fluorescent molecules have the ability to absorb light of a certain wavelength and emit light at a lower frequency (longer wavelength). This phenomenon is widely used in assays and imaging applications for example fluorescent labelling of certain molecules or items to more easily visualize them under microscope or use of near-infrared dyes which can penetrate through skin and muscle allowing imaging the location of particles or other items within a living organism. Recently, researchers at University of Queensland used mPEG-PLGA (AK026) from PolySciTech (www.polyscitech.com) to quantitatively test the fluorescence of dye loaded inside of pegylated nanoparticles and compare these results to other kinds of dye-loaded nanoparticles. Depending on the dye’s access to other dye molecules (which can reduce fluorescence due to self-quenching) and also the presence of items which may prevent the light from passing through the fluorescence intensity may be drastically altered. This research provides important fundamental understanding to dye-particle performance to optimize tracking studies and theranostic applications. Read more: Yang, Guangze, Yun Liu, and Chun-Xia Zhao. "Quantitative comparison of different fluorescent dye-loaded nanoparticles." Colloids and Surfaces B: Biointerfaces (2021): 111923. https://www.sciencedirect.com/science/article/pii/S0927776521003672

“Highlights: Many factors affect fluorescence intensity of dye-labeled NP at the same dye loading. These factors include dye distribution inside or on the surface of NP, and material shielding. A more reliable method was proposed to compare NP cell uptake. Abstract: Labeling nanoparticles with fluorescent dyes is a common approach to investigate their cell uptake and biodistribution, providing valuable information for the preclinical assessment of nanoparticles for drug delivery. However, the underlying assumption that the fluorescence intensity of dye-labeled nanoparticles correlates positively with the amount of nanoparticles taken up by cells might not be valid under some conditions, as it can be affected by many factors including dye dispersion, dye quenching, and material shading. Here we demonstrated that both nanoparticles with hydrophobic dyes encapsulated inside and nanoparticles with hydrophilic dyes conjugated on the particle surface suffer from different degrees of dye quenching, making it challenging for quantitative comparison of cell uptake of different nanoparticles. To address this challenge, we proposed a possible solution for direct comparative studies of dye-labeled nanoparticles. This work provides valuable information for designing and evaluating different nanoparticles for drug delivery applications.”

PLGA from PolySciTech used to create budesonide-loaded particles for controlled release applications from novel cardiovascular stent design

Monday, June 21, 2021, 2:47 PM ET

A good general rule of thumb for the delicate and sensitive internal processes of the human body is that living tissue does not like foreign objects to be inside of it. Often medical implants (stents, artificial joints, etc.) trigger reactions from the surrounding tissue simply due to their presence which can lead to inflammation and, in severe cases, failure of the implant and potentially severe patient morbidity or mortality. Budesonide is a steroidal anti-inflammatory which can be helpful in preventing the human immune system from attacking biomedical implants. Recently, researchers at Massachusetts Institute of Technology and Harvard Medical School used PLGA from PolySciTech (www.polyscitech.com) to create budesonide loaded particles and applied these to a custom-designed stent. This research holds promise to reduce inflammation, in-stent restenosis, and other complications which occur with cardiovascular stent emplacement. Read more: Babaee, Sahab, Yichao Shi, Saeed Abbasalizadeh, Siddartha Tamang, Kaitlyn Hess, Joy E. Collins, Keiko Ishida et al. "Kirigami-inspired stents for sustained local delivery of therapeutics." Nature Materials (2021): 1-8. https://www.nature.com/articles/s41563-021-01031-1

“Abstract: Implantable drug depots have the capacity to locally meet therapeutic requirements by maximizing local drug efficacy and minimizing potential systemic side effects. Tubular organs including the gastrointestinal tract, respiratory tract and vasculature all manifest with endoluminal disease. The anatomic distribution of localized drug delivery for these organs using existing therapeutic modalities is limited. Application of local depots in a circumferential and extended longitudinal fashion could transform our capacity to offer effective treatment across a range of conditions. Here we report the development and application of a kirigami-based stent platform to achieve this. The stents comprise a stretchable snake-skin-inspired kirigami shell integrated with a fluidically driven linear soft actuator. They have the capacity to deposit drug depots circumferentially and longitudinally in the tubular mucosa of the gastrointestinal tract across millimetre to multi-centimetre length scales, as well as in the vasculature and large airways. We characterize the mechanics of kirigami stents for injection, and their capacity to engage tissue in a controlled manner and deposit degradable microparticles loaded with therapeutics by evaluating these systems ex vivo and in vivo in swine. We anticipate such systems could be applied for a range of endoluminal diseases by simplifying dosing regimens while maximizing drug on-target effects through the sustained release of therapeutics and minimizing systemic side effects.”

PLGA from PolySciTech used in development of acetazolamide-eluting pancreatic bile stent to treat postoperative pancreatic fistula

Wednesday, June 16, 2021, 3:45 PM ET

Postoperative pancreatic fistula (POPF) remains the major cause of morbidity after pancreatic resection, affecting up to 41% of cases. It occurs due to pancreatic juices leaking from the surgically exfoliated surfaces or from the cut sections of an anastomosis (where intestinal and pancreas tubes join together). This can lead to sever abscess infections and a potentially lethal internal hemorrhage. Recently, researchers at Asan Medical Center, University of Ulsan College of Medicine, Inha University (Korea) and College of Medicine, UT Health Science Center at San Antonio (USA) used PLGA (AP132) from PolySciTech (www.polyscitech.com) to create a biodegradable tubular stent which releases acetazolamide that prevents damage from pancreatic juices. This research holds promise to improve outcomes from this common surgical complication. Read more: Park, Jung-Hoon, Jieun Park, Yejong Park, Jeon Min Kang, Dea Sung Ryu, Jeongsu Kyung, Jong Kun Jang et al. "Acetazolamide-eluting biodegradable tubular stent prevents pancreaticojejunal anastomotic leakage." Journal of Controlled Release (2021). https://www.sciencedirect.com/science/article/pii/S0168365921002972

“Highlights: AZ-BTS effectively suppresses self-digestion caused by pancreatic juice leakage. BTS with or without AZ has inhibitory effect of anastomotic stricture formation. AZ-BTS was fabricated by a multiple dip-coating technique with reliable release. The releases AZ, targets carbonic anhydrase, protects tisssues from pancreatic juice. Animal model induced a reproducible incidence of anastomotic leakage and symptoms. Abstract: Postoperative pancreatic fistula at the early stage can lead to auto-digestion, which may delay the recovery of the pancreaticojejunal (PJ) anastomosis. The efficacy and safety of an acetazolamide-eluting biodegradable tubular stent (AZ-BTS) for the prevention of self-digestion and intra-abdominal inflammatory diseases caused by pancreatic juice leakage after PJ anastomosis in a porcine model were investigated. The AZ-BTS was successfully fabricated using a multiple dip-coating process. Then, the drug amount and release profile were analyzed. The therapeutic effects of AZ were examined in vitro using two kinds of pancreatic cancer cell lines, AsPC-1 and PANC-1. The efficacy of AZ-BTS was assessed in a porcine PJ leakage model, with animals were each assigned to a leakage group, a BTS group and an AZ-BTS group. The overall mortality rates in these three groups were 44.4%, 16.6%, and 0%, respectively. Mean α-amylase concentrations were significantly higher in the leakage and BTS groups than in the AZ-BTS group on day 2–5 (p < 0.05 each all). The luminal diameters and areas of the pancreatic duct were significantly larger in the leakage group than in the BTS and AZ-BTS groups (p < 0.05 each all). These findings indicate that AZ-BTS can significantly suppress intra-abdominal inflammatory diseases caused by pancreatic juice leakage and also prevent late stricture formation at the PJ anastomotic site in a porcine model.”

PLGA-NHS and PLGA-amine from PolySciTech used in development of theranostic nanoparticle for treatment of brain cancer

Wednesday, June 16, 2021, 3:44 PM ET

Brain cancer, especially glioblastoma, remains difficult to treat due to the sensitivity of the region of the body that it affects and difficulty with delivering medicinal molecules into the brain. Recently, researchers at Indiana University School of Medicine used PLGA-NH2 (AI062) and PLGA-NHS (AI116) from PolySciTech (www.polyscitech.com) to create CD133 targeted nanoparticles loaded both with chemotherapeutic agents (temozolomide and idasanutlin) along Zirconium radio-tracer to enable both treatment of and imaging of brain cancer. This research holds promise to improve therapies against this disease in the future. Read more: Smiley, Shelby B., Yeonhee Yun, Pranav Ayyagari, Harlan E. Shannon, Karen E. Pollok, Michael W. Vannier, Sudip K. Das, and Michael C. Veronesi. "Development of CD133 Targeting Multi-Drug Polymer Micellar Nanoparticles for Glioblastoma-In Vitro Evaluation in Glioblastoma Stem Cells." Pharmaceutical Research (2021): 1-13. https://link.springer.com/article/10.1007/s11095-021-03050-8

“Abstract: Purpose: Glioblastoma (GBM) is a malignant brain tumor with a poor long-term prognosis due to recurrence from highly resistant GBM cancer stem cells (CSCs), for which the current standard of treatment with temozolomide (TMZ) alone will unlikely produce a viable cure. In addition, CSCs regenerate rapidly and overexpress methyl transferase which overrides the DNA-alkylating mechanism of TMZ, leading to resistance. The objective of this research was to apply the concepts of nanotechnology to develop a multi-drug therapy, TMZ and idasanutlin (RG7388, a potent mouse double minute 2 (MDM2) antagonist), loaded in functionalized nanoparticles (NPs) that target the GBM CSC subpopulation, reduce the cell viability and provide possibility of in vivo preclinical imaging. Methods: Polymer-micellar NPs composed of poly(styrene-b-ethylene oxide) (PS-b-PEO) and poly(lactic-co-glycolic) acid (PLGA) were developed by a double emulsion technique loading TMZ and/or RG7388. The NPs were covalently bound to a 15-nucleotide base-pair CD133 aptamer to target the CD133 antigen expressed on the surfaces of GBM CSCs. For diagnostic functionality, the NPs were labelled with radiotracer Zirconium-89 (89Zr). Results: NPs maintained size range less than 100 nm, a low negative charge and exhibited the ability to target and kill the CSC subpopulation when TMZ and RG7388 were used in combination. The targeting function of CD133 aptamer promoted killing in GBM CSCs providing impetus for further development of targeted nanosystems for localized therapy in future in vivo models. Conclusions: This work has provided a potential clinical application for targeting GBM CSCs with simultaneous diagnostic imaging.”

PLGA-Amine from PolySciTech used in development of ROS-sensitive delivery system for Alzheimer’s treatment

Tuesday, June 8, 2021, 2:00 PM ET

Oxidative stress is a common situation for cells when they are either going through an inflammatory response or in a disease state. This condition usually manifests with an increase in reactive oxygen species (HO radical, O2-, H2O2 for examples) in the cellular structure and surrounding tissue. Being able to develop a system which primarily distributes drugs to cells in a condition of oxidative stress can improve delivery for difficult to treat diseases such as cancer and Alzheimer’s disease. Researchers at University of Modena and Reggio Emilia (Italy) used PLGA-NH2 (AI062) from PolySciTech (www.polyscitech.com) to generate a PLGA-TK polymer which breaks down in response to reactive oxygen species. This research holds promise to improve therapies against ROS-related diseases. Read more: Oddone, Natalia, Tosi, Giovanni, and Barbara Ruozi. "ROS-responsive polymer conjugates and prodrugs as innovative DDS aiming for the treatment of brain diseases." University of Modena and Reggio Emilia PhD Thesis 2021 https://www.researchgate.net/profile/Natalia-Oddone/publication/352001593_ROS-responsive_polymer_conjugates_and_prodrugs_as_innovative_DDS_aiming_for_the_treatment_of_brain_diseases/links/60b4f99745851557bab32938/ROS-responsive-polymer-conjugates-and-prodrugs-as-innovative-DDS-aiming-for-the-treatment-of-brain-diseases.pdf

“In order to obtain more selective and tunable Drug Delivery Systems (DDS), “Smart” DDS that can release their drugs in response to a specific stimulus (e.g. pH, GSH and ROS), are currently under investigation. Inflammatory diseases, neurodegenerative diseases and cancer, including Glioblastoma (GBM) are all sharing a relevant oxidative stress; therefore the design of ROS- responsive DDS for the treatment of these conditions could be a smart and very encouraging approach to access to a selective and specific delivery mediated by a pathological stimulus. Thus, the aim of this PhD thesis was to develop ROS-responsive polymeric conjugates and prodrugs linked to a ROS cleavable group, namely Thioketal (TK) diacid linker that could be used for the treatment of brain diseases. Aiming to validate the use of TK- containing ROS- responsive polymers and prodrugs, we firstly performed proof-of-concept studies by synthesizing a ROSresponsive methoxy polyethylene glycol (mPEG) polymer (mPEG-TK-COOH) and, by exploiting Cy5 fluorescent dye, ROS-responsive (mPEG-TK-Cy5) and non-ROSresponsive (mPEG-Cy5) polymer conjugates. Full chemical-physical and technological characterization was performed to confirm the success in polymer conjugation and to describe chemical-physical properties of the obtained conjugates; then the ability of these conjugates to respond to ROS was validated in ROS-simulated conditions as well as assessed in vitro on Glioblastoma multiforme (GBM) cell lines. These tests were performed in close collaboration with Prof. Grabrucker, University of Limerick, Ireland, and with Prof. Boury, University of Angers, France, during a period of international mobility. Results clearly indicated that mPEG-TK-Cy5 could be selectively released in “pathological” conditions (C6 GBM cells) over “healthy” conditions (DI TNC1 astrocyte cells). Secondly, a prodrug (mPEG-TK-MPH) for the ROS- responsive release of Melphalan (MPH), which is a poorly soluble and non-selective anticancer drug, was synthetized aiming to GBM treatment. A non-ROS responsive prodrug (mPEG-MPH) was also prepared through a similar synthetic procedure. Both prodrugs were characterized and demonstrated to undergo spontaneous auto- assembling into spherical nanometric structures. In vitro cytotoxicity assays performed on GBM cells, showed that mPEG-TK-MPH was significantly more cytotoxic than mPEG-MPH on High- ROS GBM cells (C6 and U251MG cells). Remarkably, none of the prodrugs showed to be cytotoxic on Low- ROS astrocyte cells (DI TNC1), demonstrating their safety. Finally, since PLGA (polylactic-co-glycolic acid) NPs demonstrated to be promising DDS for their application in several diseases, we produced and characterized other ROS-responsive polymeric conjugates with PLGA: PLGA-TK-COOH and PLGATK-PLGA, for the selective release of surface attached and encapsulated drugs into oxidative stress featuring diseases. We were able (starting from the PLGA conjugates produced) to formulate ROS-responsive TK-surface functionalized PLGA and PLGATK-PLGA NPs, respectively. We can conclude that due to its selective cytotoxicity in High-ROS GBM cells without being toxic to “healthy” cells, our developed ROS-responsive prodrugs show encouraging results for GBM treatment. On the other hand, the ROS-responsive PLGA NPs developed during this PhD project, could be considered as promising starting point for their future application in GBM as well as in relevant neurodegenerative diseases as Alzheimer’s disease.”

PLGA-PEG-Maleimide from PolySciTech used in development of nanoparticles for treating CNS-associated tuberculosis.

Tuesday, June 1, 2021, 3:33 PM ET

Tuberculosis is a bacterial disease which most commonly infects the lungs however it can spread to other parts of the body. This disease is treatable in most parts of the body using antibiotic agents however is difficult to treat in the brain due to the blood-brain-barrier. Recently, researchers at Universidade Federal do Rio de Janeiro, Oswaldo Cruz Foundation, (Brazil), Universidade do Porto (Portugal) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create labeled nanoparticles for treatment of tuberculosis across the blood-brain-barrier. This research holds promise to improve therapeutic options for this lethal disease. Read more: de Castro, Renata Ribeiro, Flavia Almada do Carmo, Cláudia Martins, Alice Simon, Valeria Pereira de Sousa, Carlos Rangel Rodrigues, Lucio Mendes Cabral, and Bruno Sarmento. "Clofazimine functionalized polymeric nanoparticles for brain delivery in the tuberculosis treatment." International Journal of Pharmaceutics 602 (2021): 120655. https://www.sciencedirect.com/science/article/pii/S0378517321004609

“Highlights Clofazimine-loaded PLGA-PEG nanoparticles (NP-CFZ) were produced by nanoprecipitation. NP-CFZ were functionalized with a peptide (NP-CFZ-Pep) that binds transferrin receptor. NP-CFZ-Pep reduced drug toxicity and enhanced drug permeability across hCMEC/D3 cell. NP-CFZ-Pep can be administered by intravenous route and drive the drug to the brain. The NP-CFZ-Pep is promising to central nervous system tuberculosis treatment. Central nervous system tuberculosis (CNS-TB) is the most severe form of the disease especially due to the inability of therapeutics to cross the blood–brain barrier (BBB). Clofazimine (CFZ) stands out for presenting high in vitro activity against multi-drug resistant strains of Mycobacterium tuberculosis, however, CFZ physicochemical and pharmacokinetics properties limit drug penetration into the CNS and, consequently, its clinical use. The aim of this work was to develop polymeric nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) loaded with CFZ and functionalized with a transferrin receptor (TfR)-binding peptide, aiming brain drug delivery for CNS-TB treatment by the intravenous route. The poor water solubility and high lipophilicity of CFZ was overcome through its entrapment into PLGA-PEG NPs manufactured by both conventional and microfluidic techniques using the nanoprecipitation principle. In vitro studies in brain endothelial hCMEC/D3 cells demonstrated that CFZ incorporation into the NPs was advantageous to reduce drug cytotoxicity. The TfR-binding peptide-functionalized NPs showed superior cell interaction and higher CFZ permeability across hCMEC/D3 cell monolayers compared to the non-functionalized NP control, thus indicating the efficacy of the functionalization strategy on providing CFZ transport through the BBB in vitro. The functionalized NPs demonstrate suitability for CFZ biological administration, suggested with low plasma protein binding, off-target biodistribution and precise delivery of CFZ towards the brain parenchyma. Keywords: Brain delivery Clofazimine Targeted nanoparticles Transferrin-receptor Tuberculosis treatment”

PLGA from PolySciTech used in development of glucose/transferrin targeted nanoparticles

Tuesday, June 1, 2021, 3:32 PM ET

Due to their extremely small size, nanoparticles have the capacity to be uptaken into cells via a variety of mechanisms. The potential for a human cell to internalize a given nanoparticle depends on a variety of factors about the cell as well as for the nanoparticle and surface modifications can improve the uptake of nanoparticles. Recently, researchers at Qatar University (Qatar) used PLGA (AP045) and PLGA-Glucose (AP027) from PolySciTech (www.polyscitech.com) to create targeted nanoparticles and track their uptake against cancer cells. This research holds promise to improve drug-delivery methodology. Read More: Sarra Benammar, Fatima Mraiche, Jensa Mariam Joseph, Katerina Goracinova “Glucose and transferrin liganded PLGA nanoparticles internalization in Non-small cell lung cancer cells” Poster QUARFE 2020 https://qspace.qu.edu.qa/handle/10576/16810

“Introduction: Recently, after a decade of confusing results, several studies pointed out that overexpression of GLUT1 (glucose transporter 1) is a biomarker of worse prognosis in NSCLC. Nonetheless, the presence of Transferrin (Tf receptor), which is overexpressed in most cancer tissues and most lung cancers as well, in NSCLC is also an indicator of very poor prognosis. Therefore, these ligands can be used for active targeting of lung cancer cells and improved efficacy of internalization of cancer therapy using nanomedicines. Objectives: Having the background, the main goal of the project was the assessment of the influence of the glucose and transferrin ligands on the efficacy of internalization of the designed (i) glucose decorated PLGA (poly lactic-co-glycolic acid) nanoparticles (Glu-PLGA NPs) and (ii) transferrin decorated PLGA nanoparticles (Tf-PLGA NPs) in comparison to (iii) non-liganded PLGA NPs using a A549 lung cancer cells. Methods: Glu-PLGA NPs, Tf-PLGA NPs and PLGA NP - fluorescently labelled), were designed using a sonication assisted nanoprecipitation method. Further, physicochemical properties characterization (particle size analysis, zeta potential, FTIR analysis, DSC analysis), cytotoxicity evaluation using MTT test, and cell internalization studies of DTAF labelled NPs using fluorimetry in A549 NSCLC cell line were performed. Results: The results pointed to a significantly improved internalization rate of the liganded compared to PLGA NPs. Glu-PLGA NPs showed higher internalization rate compared to Tf-PLGA and PLGA NPs, in the serum-supplemented and serum-free medium even at normal levels of glucose in the cell growth medium. Conclusion: The developed nanocarriers offer unique advantages of enhanced targetability, improved cell internalization and decreased toxicity which makes them promising solution for current therapeutic limitations ”

PLGA-PEG polymers from PolySciTech used in development of acoustic-microfluidic nanoparticles

Tuesday, May 18, 2021, 1:39 PM ET

Nanoparticles are an excellent means to deliver poorly soluble or difficult to target drug molecules to bodily systems. There are many methods to generate particles however the use of microfluidics provides for improved control of the manufacturing process. Recently, researchers at Duke University (North Carolina, USA) used PLGA-PEG-COOH (AI056, AI184, AI080) and PLGA-NH2 (AI017) from PolySciTech (www.polyscitech.com) to develop an acoustic-microfluidic method for nanoparticle generation. This research holds promise to improve drug delivery methodologies in the future. Read more: Zhao, Shuaiguo, Po-Hsun Huang, Heying Zhang, Joseph Rich, Hunter Bachman, Jennifer Ye, Wenfen Zhang et al. "Fabrication of tunable, high-molecular-weight polymeric nanoparticles via ultrafast acoustofluidic micromixing." Lab on a Chip (2021). https://pubs.rsc.org/en/content/articlehtml/2021/lc/d1lc00265a

“Abstract: High-molecular-weight polymeric nanoparticles are critical to increasing the loading efficacy and tuning the release profile of targeted molecules for medical diagnosis, imaging, and therapeutics. Although a number of microfluidic approaches have attained reproducible nanoparticle synthesis, it is still challenging to fabricate nanoparticles from high-molecular-weight polymers in a size and structure-controlled manner. In this work, an acoustofluidic platform is developed to synthesize size-tunable, high-molecular-weight (>45 kDa) poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA–PEG) nanoparticles without polymer aggregation by exploiting the characteristics of complete and ultrafast mixing. Moreover, the acoustofluidic approach achieves two features that have not been achieved by existing microfluidic approaches: (1) multi-step (≥2) sequential nanoprecipitation in a single device, and (2) synthesis of core–shell structured PLGA–PEG/lipid nanoparticles with high molecular weights. The developed platform expands microfluidic potential in nanomaterial synthesis, where high-molecular-weight polymers, multiple reagents, or sequential nanoprecipitations are needed.”

PLGA from PolySciTech used in a systematic study of nanoparticle emulsion stability by polymer properties

Monday, May 17, 2021, 1:58 PM ET

Nanoparticles references small particulate material in the nanometer scale range (<1 micrometer in size). Since the particles are significantly smaller than a human cell (~ 10 um) they can, under the right conditions, possess the ability to penetrate into cells and delivery drug payloads. They also provide for a wide array of other properties (high surface-to-area ratio, high activity, etc.) due to their small size and surface properties. To prevent particles from simply clumping together and settling out from a slurry, they must be stabilized by one mechanism or another. Recently researchers at Institut Galien Paris-Saclay, Université Paris-Saclay, and Sorbonne Université (France) use PLGA (AP041, AP082, AP022, AP023) from PolySciTech (www.polyscitech.com) to produce nanoparticles under a wide array of conditions. They systematically tested the resultant nanoparticle properties with an emphasis on emulsion stabilization approach. This research holds promise to improve the development of drug-delivery nanoparticles in the future. Read more: Robin, Baptiste, Claire Albert, Mohamed Beladjine, François-Xavier Legrand, Sandrine Geiger, Laurence Moine, Valérie Nicolas et al. "Tuning morphology of Pickering emulsions stabilised by biodegradable PLGA nanoparticles: How PLGA characteristics influence emulsion properties." Journal of Colloid and Interface Science 595 (2021): 202-211. https://www.sciencedirect.com/science/article/pii/S0021979721003544

“Abstract: In this study, we proved that the stabilisation of Pickering emulsions by polymer nanoparticles (NPs) heavily depends on polymer characteristics. We prepared NPs with four poly(lactide–co–glycolide) polymers (PLGA), of different molar masses (14,000 and 32,000 g/mol) and end groups (acid or alkylester). NPs were either bare (without stabilising polymer) or covered by polyvinyl alcohol (PVA). Pickering emulsions were prepared by mixing NP aqueous suspensions with various amounts of oil (Miglyol 812 N). First, NP wettability was directly affected by PLGA end group: ester-ending PLGA led to more hydrophobic NPs, compared to acid-ending PLGA. This effect of the end group could be slightly enhanced with smaller molar mass. Thus, bare PLGA NPs stabilised different types of emulsions (W/O/W and W/O), following Finkle’s rule. However, the effect of PLGA characteristics was masked when NPs were covered by PVA, as PVA drove the stabilisation of O/W emulsions. Secondly, PLGA molar mass and end group also influenced its glass transition temperature (Tg), with spectacular consequences on emulsion formation. Indeed, the shortest ester-ending PLGA exhibited a Tg close to room temperature, when measured in the emulsion. This Tg, easily exceeded during emulsification process, led to a soft solid emulsion, stabilised by a network of NP debris. Keywords: Pickering emulsions PLGA Nanoparticles Polymer end group Molar mass PVA Wettability Glass transition temperature Emulsion type Nanoparticle organization”

PLGA from PolySciTech used in development of Se-CeO2 nanoparticle preparation for treatment of spinal-cord injuries

Tuesday, May 11, 2021, 9:48 AM ET

Until very recently, injuries to the spinal column almost certainly lead to a lifetime of paralysis. Modern technology, however, is bringing about the potential for healing the delicate nerve tissues within the spinal column to restore functionality to the paralyzed portions of a patient’s body. Recently, researchers at Zhengzhou University (China) used PLGA (AP040) from PolySciTech (www.polyscitech.com) to develop nanoparticles including Se/CeO2 for use in improving healing of the spinal cord after injuries. This research holds promise to serve as a treatment for injury-induced paralysis. Read more: Wang, Xiaoying, Biao Li, Jingjing Fan, Shanshan Tian, and Xiangyang Wei. "Novel nanoformulated combination of Se and CeO2 particles loaded polylactic‐co‐glycolic acid vesicle to improved anti‐inflammation and auto‐regenerative for the treatment and care of spinal cord injury." Applied Organometallic Chemistry: e6269. https://onlinelibrary.wiley.com/doi/abs/10.1002/aoc.6269

“Abstract: Polymer functionalized nanoparticles (NPs) have a great attention in biomedical applications owing to their unique properties like regenerative antioxidant, anti‐inflammatory, auto‐catalytic properties, and biocompatibility. In this current work, we demonstrated a facile synthesis of Se‐CeO2 via chemical method followed by precipitation method. The prepared Se NPs were characterized by ultraviolet–visible (UV‐vis) spectroscopy, and the size and morphology of the NPs were analysed using transmission electron microscopy (TEM). Meanwhile, Se‐CeO2 NPs loaded on polylactic‐co‐glycolic acid (PLGA) nanocarrier were characterised by Fourier transform infrared (FT‐IR), scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), TEM, and energy dispersive X‐ray analysis (EDAX) mapping techniques. The morphological and spectroscopic investigations of prepared nanomaterials have exhibited favourable morphological structure and chemical interactions with respective polymeric molecules, which established that nanovesicle suitability for the SCI functional recovery. We first investigated Se nanoformulated CeO2 material for the potential healing of in vitro spinal cord study. Our results demonstrated that preparation of NPs loaded PLGA nanocarrier has provide effective spinal cord regeneration and imply that it was explored that promising nanocarrier in the SCI treatment. Se‐NPs encapsulated CeO2 nanostructures administrations for SCI therapies have greatly suppressed oxidative stress and induced anti‐inflammatory action, which leads to prospective therapeutic benefits of spinal cord regeneration. These investigative results demonstrate that Se‐CeO2 NPs with PLGA carrier could have great attention for effecient functional recovery treatment and care for spinal cord injury.”

PLGA-PEG-Mal from PolySciTech used in development of nanoparticle-based breast cancer therapy

Wednesday, May 5, 2021, 10:25 AM ET

The primary limitations on chemotherapeutics are related to their safety profiles as the damage these agents cause to normally healthy tissue is non-trivial and the side effects can be severe. Recently, researchers at Harbin Medical University and Tsinghua University (China) Used mPEG-PLGA (AK037) and Mal-PEG-PLGA (AI020) from PolySciTech (www.polyscitech.com) to create anti-HER2 targeted nanoparticles for targeting of breast cancer. This research holds promise to improve cancer therapies in the future. Read more: Ni, Ling, and You-Xin Li. "Anti-Human Epidermal Growth Factor Receptor 2 Single-Chain Fv Fragment-Decorated DM1 Nanoparticles for Specific Targeting of Human Epidermal Growth Factor Receptor 2-Positive Breast Tumor Cells." Journal of Biomedical Nanotechnology 17, no. 3 (2021): 447-455. https://www.ingentaconnect.com/contentone/asp/jbn/2021/00000017/00000003/art00010

“Abstract: Purpose: Although monoclonal antibodies are used to decorate nanoparticles to target specific cells, penetration of tumor tissues by monoclonal antibodies is limited by their large size. Therefore, we prepared DM1 nanoparticles decorated with the small anti-HER2 single-chain Fv fragment (scFvHER2) of trastuzumab (TMAB) for targeting to human epidermal growth factor receptor 2 (HER2) overexpressing in breast cancer effectively. Methods: ScFvHER2 fragment was coupled with DM1 nanoparticles (NPs) via covalent thiol-maleimide linkages. Their physicochemical properties, uptake by cells, and toxicity to tumor cells were investigated. Their vivo biodistribution was assessed employing liquid chromatographytandem mass spectrometry, while their antitumor activity was investigated in nude mice burdened with BT-474 tumor. Results: Viability of BT-474 cells incubated with scFvHER2-DM1-Nanoparticles (scFv-DM1-NPs) was significantly lower than that of BT-474 cell treated with TMAB-DM1-Nanoparticles (TMAB-DM1-NPs) (P < 0 05). Uptake by cells of scFvDM1-NPs was significantly higher than TMAB-DM1-NPs (P < 0 01). Accumulation of scFv-DM1-NPs in tumor tissue was notably higher than TMAB-DM1-NPs (P < 0 05). scFv-DM1-NPs exhibited improved antitumor effects compared to TMABDM1-NPs (P < 0 05), showing a tumor inhibition rate of more than 70%. Conclusions: ScFvHER2 fragment could serve as a more effective targeting ligand than TMAB, and scFv-DM1-NPs could be developed as a possible drug delivery system to target HER2-positive breast cancer.”

PLGA from PolySciTech used in development of novel hydrogel-supported long-acting injectable formulation

Thursday, April 29, 2021, 10:17 AM ET

All medicinal molecules administered to a patient will eventually be removed from the body by a variety of clearance mechanisms (e.g. excreted in urine, destroyed in the liver, exhaled through lungs etc.) and the rate of this clearance is described as the biological half-life of the particular molecule which is usually in the order of magnitude of minutes to hours. For an injected medicine, this means that to keep a therapeutic dose in a patient there would have to be repeating doses to replace the medicine that is cleared by the body. This is inconvenient and difficult to maintain compliance as patients generally don’t enjoy being repeatedly stabbed with a needle so it is better to provide a long-acting injectable formulation which requires only a single injected of the drug molecule encapsulated in a material which slowly releases the drug out into the bloodstream over an extended period of time. Recently, researchers from Kangwon National University, Chonnam National University, Seoul National University (Korea), Terasaki Institute for Biomedical Innovation, and University of California, Los Angeles, used PLGA (AP059) from PolySciTech (www.polyscitech.com) to create donepezil-loaded microparticles. These particles were subsequently loaded into a novel HA hydrogel system to create a long-acting injectable. This research holds promise to provide for improved drug-release systems in the future. Read more: Hwang, ChaeRim, Song Yi Lee, Han-Jun Kim, KangJu Lee, Junmin Lee, Dae-Duk Kim, and Hyun-Jong Cho. "Polypseudorotaxane and polydopamine linkage-based hyaluronic acid hydrogel network with a single syringe injection for sustained drug delivery." Carbohydrate Polymers (2021): 118104. https://www.sciencedirect.com/science/article/pii/S0144861721004914

“Highlights: Hyaluronic acid-dopamine-polyethylene glycol (HD-PEG) was synthesized and identified. HD-PEG was threaded with alpha-cyclodextrin (α-CD) and pH was adjusted to 8.5. Polypseudorotaxane structure and polydopamine bond-based hydrogel was fabricated. Donepezil-loaded microspheres were embedded in hydrogel system for sustained release. Rheological features of injectable hydrogel were tuned for slow biodegradation. Abstract: Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection. Keywords: Crosslinked hydrogel Polypseudorotaxane Polydopamine Single syringe injection Slow biodegradation Sustained drug release”

PLGA from PolySciTech used in development of Notch-signaling delivery nanoparticles to reduce fetal developmental problems

Monday, April 26, 2021, 11:09 AM ET

Notch signaling indicates a specific cellular signaling pathway which is involved in embryonic development. Failure for this pathway to continue its signaling cascade can lead to developmental problems in a growing embryo. Recently, researchers at University of Texas at Arlington used two different molecular weights of PLGA (AP081, AP154) from PolySciTech (www.polyscitech.com) to create nanoparticles for intracellular plasmid delivery. This research may help reduce fetal developmental problems. Read more: Messerschmidt, Victoria L., Aneetta E. Kuriakose, Uday Chintapula, Samantha Laboy, Thuy Thi Dang Truong, LeNaiya A. Kydd, Justyn Jaworski, Kytai T. Nguyen, and Juhyun Lee. "Notch Intracellular Domain Plasmid Delivery via Poly (lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling." bioRxiv (2021). https://www.biorxiv.org/content/10.1101/2021.04.16.440241v1.abstract

“Abstract: Notch signaling is a highly conserved signaling system that is required for embryonic development and regeneration of organs. When the signal is lost, maldevelopment occurs and leads to a lethal state. Liposomes and retroviruses are most commonly used to deliver genetic material to cells. However, there are many drawbacks to these systems such as increased toxicity, nonspecific delivery, short half-life, and stability after formulation. We utilized the negatively charged and FDA approved polymer poly(lactic-co-glycolic acid) to encapsulate Notch Intracellular Domain-containing plasmid in nanoparticles. In this study, we show that primary human umbilical vein endothelial cells readily uptake the nanoparticles with and without specific antibody targets. We demonstrated that our nanoparticles also are nontoxic, stable over time, and compatible with blood. We also determined that we can successfully transfect primary human umbilical vein endothelial cells (HUVECs) with our nanoparticles in static and dynamic environments. Lastly, we elucidated that our transfection upregulates the downstream genes of Notch signaling, indicating that the payload was viable and successfully altered the genetic downstream effects.”

Thermogelling PLGA-PEG-PLGA used in development of 4-aminopyridine delivery system for treatment of paralysis

Monday, April 26, 2021, 11:08 AM ET

Paralysis can occur in cases of traumatic injuries from a variety of causes (car-crash, military action, industrial accidents, etc.) which lead to either severing or substantial injury to nerve tissue. Because nerve tissue does not normally heal itself, often this paralysis can be permanent leaving a patient unable to move from the point of the injury down (i.e. confined to a wheelchair). Recently, researchers at Pennsylvania State University used PLGA-PEG-PLGA (AK097) to create a delivery system for 4-aminopyridine, a drug which acts to enhance nerve repair. This research holds promise to improve treatment options for debilitating injuries. Read more: Manto, Kristen M., Prem Kumar Govindappa, Daniele Parisi, Zara Karuman, Brandon Martinazzi, John P. Hegarty, MA Hassan Talukder, and John C. Elfar. "(4-Aminopyridine)–PLGA–PEG as a Novel Thermosensitive and Locally Injectable Treatment for Acute Peripheral Nerve Injury." ACS Applied Bio Materials (2021). https://pubs.acs.org/doi/abs/10.1021/acsabm.0c01566

“Traumatic peripheral nerve injury (TPNI) represents a major medical problem that results in loss of motor and sensory function, and in severe cases, limb paralysis and amputation. To date, there are no effective treatments beyond surgery in selective cases. In repurposing studies, we found that daily systemic administration of the FDA-approved drug 4-aminopyridine (4-AP) enhanced functional recovery after acute peripheral nerve injury. This study was aimed at constructing a novel local delivery system of 4-AP using thermogelling polymers. We optimized a thermosensitive (4-AP)–poly(lactide-co-glycolide)–b-poly(ethylene glycol)–b-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) block copolymer formulation. (4-AP)–PLGA–PEG exhibited controlled release of 4-AP both in vitro and in vivo for approximately 3 weeks, with clinically relevant safe serum levels in animals. Rheological investigation showed that (4-AP)–PLGA–PEG underwent a solution to gel transition at 32 °C, a physiologically relevant temperature, allowing us to administer it to an injured limb while subsequently forming an in situ gel. A single local administration of (4-AP)–PLGA–PEG remarkably enhanced motor and sensory functional recovery on post-sciatic nerve crush injury days 1, 3, 7, 14, and 21. Moreover, immunohistochemical studies of injured nerves treated with (4-AP)-PLGA-PEG demonstrated an increased expression of neurofilament heavy chain (NF-H) and myelin protein zero (MPZ) proteins, two major markers of nerve regeneration. These findings demonstrate that (4-AP)–PLGA–PEG may be a promising long-acting local therapeutic agent in TPNI, for which no pharmacologic treatment exists.”

Mal-PEG-PLGA from PolySciTech used in development of iron nanoparticle based thermal treatment of cancer

Tuesday, April 20, 2021, 3:36 PM ET

There are many ways to treat cancer all of which have their benefits and risks. One method is to locally heat the cancer up to 45 ⁰C (normal human body temperature is 37 ⁰C) so that the cancer cells break down from the excess heat. For obvious reasons, this heating must be localized to the smallest possible area to reduce damage to the patient. Recently, researchers at Shanghai Jiao Tong University (China) used PLGA-PEG-Mal (AI110) and mPEG-PLGA (AK029) from PolySciTech (www.polyscitech.com) to create iron-oxide loaded nanoparticles. These were used to sensitize cancer cells which were then exposed to near-IR light to create localized heating as a way to destroy cancer cells. This research holds promise to improve treatment options against cancer. Read more: ​​Xie, Shaowei, Wenshe Sun, Chunfu Zhang, Baijun Dong, Jingxing Yang, Mengfei Hou, Liqin Xiong, Biao Cai, Xuesong Liu, and Wei Xue. "Metabolic Control by Heat Stress Determining Cell Fate to Ferroptosis for Effective Cancer Therapy." ACS Nano (2021). https://pubs.acs.org/doi/pdf/10.1021/acsnano.1c00380

“Flexible manipulation of the fate of cancer cells through exogenous stimulation-induced metabolic reprogramming could handle the cellular plasticity-derived therapies resistance, which provides an effective paradigm for the treatment of refractory and relapsing tumors in clinical settings. Herein, we demonstrated that moderate heat (45 °C) could significantly regress the expression of antioxidants and trigger specific lipid metabolic reprogramming in cancer cells synergized with iron oxide nanoparticles (Fe3O4 NPs). This metabolic control behavior destroyed the tumor redox homeostasis and produced overwhelming lipid peroxides, consequently sensitizing the tumor to ferroptosis. Based on these findings, a heat-triggered tumor-specific ferroptosis strategy was proposed by the rational design of a polypeptide-modified and 1H-perfluoropentane (1H-PFP)-encapsulated Fe3O4-containing nanoformulation (GBP@Fe3O4). When irradiated by an 808 nm laser, the phase transition of 1H-PFP was triggered by localized moderate heat (45 °C), leading to burst release of Fe3O4in situ to produce potent reactive oxygen species through the Fenton reaction in the tumor microenvironment. Together with the antioxidant inhibition response and distinctive lipid metabolic reprogramming by heat stress, this oxidative damage was amplified to induce tumor ferroptosis and achieve sufficient antitumor effects. Importantly, we confirmed that ACSBG1, an acyl-CoA synthetase, was the key pro-ferroptotic factor in this heat-induced ferroptosis process. Moreover, knockout of this gene could realize cancer cell death fate conversion from ferroptosis to non-ferroptotic death. This work provides mechanistic insights and practical strategies for heat-triggered ferroptosis in situ to reduce the potential side effects of direct ferroptosis inducers and highlights the key factor in regulating cell fate under heat stress. KEYWORDS: metabolic reprogramming ferroptosis heat stress iron oxide nanoparticles cancer therapy”

PLGA-PEG-Mal used in development of Polymer-DNA based nanoparticles for immunotherapy of cancer

Tuesday, April 20, 2021, 9:48 AM ET

Maleimide is a chemical moiety that can chemically react with thiol (-SH) units at neutral pH and room temperature (i.e. gentle conditions unlikely to damage biomolecules) to bind to them. A useful property of this is attaching a biological molecule (protein, DNA, etc.) which has a thiol unit on it to synthetic polymer such as PEG-PLGA to create a combination semi-synthetic material. Recently, PLGA-PEG-Mal (AI053) from PolySciTech (www.polyscitech.com) used in development of polymer-DNA nanoparticles for use in immunotherapy approaches. This research holds promise to improve therapies against cancer. Read more: Huang, Xiao, Jasper Z. Williams, Ryan Chang, Zhongbo Li, Cassandra E. Burnett, Rogelio Hernandez-Lopez, Initha Setiady et al. "DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation." Nature Nanotechnology 16, no. 2 (2021): 214-223. https://www.nature.com/articles/s41565-020-00813-z

“Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy, and a high level of control over surface functionalization is essential for immune cell modulation. Here, we developed biocompatible immune cell-engaging particles (ICEp) that use synthetic short DNA as scaffolds for efficient and tunable protein loading. To improve the safety of chimeric antigen receptor (CAR) T cell therapies, micrometre-sized ICEp were injected intratumorally to present a priming signal for systemically administered AND-gate CAR-T cells. Locally retained ICEp presenting a high density of priming antigens activated CAR T cells, driving local tumour clearance while sparing uninjected tumours in immunodeficient mice. The ratiometric control of costimulatory ligands (anti-CD3 and anti-CD28 antibodies) and the surface presentation of a cytokine (IL-2) on ICEp were shown to substantially impact human primary T cell activation phenotypes. This modular and versatile biomaterial functionalization platform can provide new opportunities for immunotherapies.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.29729604721069 seconds)


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