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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PLGA-PEG-Mal from PolySciTech used in investigating hypergravity effects on intestinal permeability during space travel.

Tuesday, April 6, 2021, 1:53 PM ET

Various physiological conditions are affected by surrounding environment. In general, on Earth, the gravitational force is constant (1G) in the absence of rapid acceleration or spinning motion. Within the context of an eventual time when space-travel becomes common-place enough for such parameters as gravitational force to matter, there should be at least some understanding around intestinal uptake under this condition. Recently, researchers at Universidade do Porto (Portugal), European Space Agency, Amsterdam University Medical Center (Netherlands), and CESPU (Portugal) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create particles decorated with Fc receptors to investigate intestinal uptake under varying gravitational forces. Having some understanding around this process will become relevant in the future with increased space travel. Read more: Azevedo, Cláudia, Maria Helena Macedo, Andreia Almeida, Soraia Pinto, Jack JWA van Loon, and Bruno Sarmento. "The effect of hypergravity in intestinal permeability of nanoformulations and molecules." European Journal of Pharmaceutics and Biopharmaceutics (2021). https://www.sciencedirect.com/science/article/pii/S0939641121000801

“Highlights: First study describing the impact of hypergravity on intestinal absorption. Metabolic activity and integrity of intestinal cells are not influenced by hypergravity. Hypergravity can affect the expression of different proteins on intestinal cells. The effect of hypergravity on intestinal absorption is dependent of the molecule and absorption mechanism. Abstract: The oral administration of drugs remains a challenge due to rapid enzymatic degradation and minimal absorption in the gastrointestinal tract. Mechanical forces, namely hypergravity, can interfere with cellular integrity and drug absorption, and there is no study describing its influence in the intestinal permeability. In this work, it was studied the effect of hypergravity on intestinal Caco-2 cells and its influence in the intestinal permeability of different nanoformulations and molecules. It was shown that the cellular metabolic activity and integrity were maintained after exposure to different gravity-levels (g-levels). Expression of important drug transporters and tight junctions’ proteins was evaluated and, most proteins demonstrated a switch of behavior in their expression. Furthermore, paracellular transport of FITC-Dextran showed to significantly increase with hypergravity, which agrees with the decrease of transepithelial electrical resistance and the increase of claudin-2 at higher g-levels. The diffusion of camptothecin released from polymeric micelles revealed a significant decrease, which agrees with the increased expression of the P-gp observed with the increase in g-levels, responsible for pumping this drug out. The neonatal Fc receptor-mediated transport of albumin-functionalized nanoparticles loaded with insulin showed no significant changes when increasing the g-levels. Thus, this study supports the effect of hypergravity on intestinal permeability is dependent on the molecule studied and the mechanism by which it is absorbed in the intestine.”

Thermogelling PLGA-PEG-PLGA from PolySciTech used in the development of Albumin-delivery system

Tuesday, April 6, 2021, 1:52 PM ET

Albumin is a naturally occurring protein that is commonly used to transport molecules which makes it an attractive target for use in drug delivery. Recently, researchers at University of Mississippi used PLGA-PEG-PLGA (AK097) from PolySciTech (www.polyscitech.com) to develop injectable albumin systems and used fluorescence to track the albumin motion and uptake. This research holds promise to provide for improved drug-delivery formulations in the future. Read more: Patel, Nidhi, Nan Ji, Yingzhe Wang, Xingcong Li, Nigel Langley, and Chalet Tan. "Subcutaneous Delivery of Albumin: Impact of Thermosensitive Hydrogels." AAPS PharmSciTech 22, no. 3 (2021): 1-8. https://link.springer.com/article/10.1208/s12249-021-01982-3

“Abstract: Albumin demonstrates remarkable promises as a versatile carrier for therapeutic and diagnostic agents. However, noninvasive delivery of albumin-based therapeutics has been largely unexplored. In this study, injectable thermosensitive hydrogels were evaluated as sustained delivery systems for Cy5.5-labeled bovine serum albumin (BSA-Cy5.5). These hydrogels were prepared using aqueous solutions of Poloxamer 407 (P407) or poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA), which could undergo temperature-triggered phase transition and spontaneously solidify into hydrogels near body temperature, serving as in situ depot for tunable cargo release. In vitro, these hydrogels were found to release BSA-Cy5.5 in a sustained manner with the release half-life of BSA-Cy5.5 from P407 and PLGA-PEG-PLGA hydrogels at 16 h and 105 h, respectively. Without affecting the bioavailability, subcutaneous administration of BSA-Cy5.5-laden P407 hydrogel resulted in delayed BSA-Cy5.5 absorption, which reached the maximum plasma level (Tmax) at 24 h, whereas the Tmax for subcutaneously administered free BSA-Cy5.5 solution was 8 h. Unexpectedly, subcutaneously injected BSA-Cy5.5-laden PLGA-PEG-PLGA hydrogel did not yield sustained BSA-Cy5.5 plasma level, the bioavailability of which was significantly lower than that of P407 hydrogel (p < 0.05). The near-infrared imaging of BSA-Cy5.5-treated mice revealed that a notable portion of BSA-Cy5.5 remained trapped within the subcutaneous tissues after 6 days following the subcutaneous administration of free solution or hydrogels, suggesting the discontinuation of BSA-Cy5.5 absorption irrespective of the formulations. These results suggest the opportunities of developing injectable thermoresponsive hydrogel formulations for subcutaneous delivery of albumin-based therapeutics.”

mPEG-PLA from PolySciTech used in development of solid-tumor immunotherapy

Tuesday, April 6, 2021, 1:51 PM ET

Immunotherapy is a process by which the human immune system is leveraged to attack the cancer directly. This must be done with care, however, as the human immune system can cause a great deal of damage if it is not well directed even potentially killing a patient through anaphylaxis. For this reason, localized immunotherapy is better than priming the systemic immune system for attack. Recently, researchers at Cello Therapeutics, Inc. and University of California San Diego used PEG-PLA (AK054) from PolySciTech (www.polyscitech.com) to create pegylated nanoparticles. The used these to test the impact of toll-like receptor agonists on immune response in solid tumors. This research holds promise to improve cancer therapies in the future. Read more: Bahmani, Baharak, Hua Gong, Brian T. Luk, Kristofer J. Haushalter, Ethel DeTeresa, Mark Previti, Jiarong Zhou et al. "Intratumoral immunotherapy using platelet-cloaked nanoparticles enhances antitumor immunity in solid tumors." Nature Communications 12, no. 1 (2021): 1-12. https://www.nature.com/articles/s41467-021-22311-z

“Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.”

PLGA from PolySciTech used in development of chemo-catalytic therapy for treatment of cancer

Tuesday, April 6, 2021, 1:50 PM ET

Despite their exotic structures, enzymes are merely machines of the body which individually serve very simple functions based on their chemical reactive sites and their overall shape. This opens up the potential to make ‘artificial’ enzymes simply by providing an item which has a similar shape and chemical reactivity, regardless of its overall chemical design. One method of treating cancer is to generate nanoparticles which have the ability to behave like enzymes in catalyzing certain interactions which lead to destruction of the cancer cells. This can be combined with other forms of chemotherapy for a powerful treatment method. Recently, researchers at Yangzhou University, Chinese Academy of Sciences, and First Affiliated Hospital of Soochow University (China) used PLGA (AP132) from PolySciTech (www.polyscitech.com) to create manganese-oxide based artificial oxidase-enzyme like structures and combined these with artesunate drug. This research holds promise to improve therapies against cancer. Read more: Xi, Juqun, Yaling Huang, Jie Chen, Jingjing Zhang, Lizeng Gao, Lei Fan, and Xiaodong Qian. "Artesunate-loaded poly (lactic-co-glycolic acid)/polydopamine-manganese oxides nanoparticles as an oxidase mimic for tumor chemo-catalytic therapy." International Journal of Biological Macromolecules (2021). https://www.sciencedirect.com/science/article/pii/S0141813021006590

“Conventional tumor chemotherapy is limited by its low therapeutic efficacy and side effects, which severely hold back its further application as a first-line agent in clinic. To improve the cure efficacy of cancer, nanozyme with enzyme-like activity has now been extensively investigated as a new strategy for tumor treatment. Herein, an anti-tumor platform based on manganese oxides (MnOx) modified poly (lactic-co-glycolic acid) (PLGA)@polydopamine (PDA) nanoparticles (PP-MnOx NPs) as an oxidase mimic was developed. PP-MnOx NPs could not only produce abundant reactive oxygen species to inhibit tumor growth taking advantage of their oxidase-like activity, but also encapsulate and release antitumor drug (artesunate) to function as chemotherapy, achieving remarkable synergistic chemo-catalytic therapeutic effects. As an oxidase mimics, PP-MnOx NPs induced the decrease of mitochondrial membrane potential, down-regulation of Bcl-2, as well as activation of Bax and Caspase-3, demonstrating that the apoptosis triggered by PP-MnOx NPs was mediated via mitochondrial pathways. Importantly, the artesunate in PP-MnOx NPs further promoted this apoptosis. In addition, Mn ions released from PP-MnOx NPs facilitated the tumor-microenvironment-specific T1-weighted magnetic resonance imaging. Taken together, this study well clarifies the antitumor mechanism of artesunate-loaded PP-MnOx NPs and offer a synergistic chemo-catalytic strategy for tumor theranostics. Keywords: MnOx modified PLGA/polydopamine nanoparticles Oxidase Reactive oxygen species Chemo-catalytic tumor therapy”

PEG-PCL/PEG-PLA polymers from PolySciTech used in research on structure of self-assembled nanocarriers

Tuesday, April 6, 2021, 1:46 PM ET

Despite their popular use, much remains to be learned about the structure and nature of self-assembled PEGylated nanocarriers comprised of PEG-block polymers. One means to do this is to load tetra tert-butyl zinc(II) phthalocyanine spectroscopic probes into the carrier and then bombard them with radio-frequency electromagnetic radiation under powerful magnetic fields and measure their UV-Vis spectra, as one normally does. Recently, researchers at Wroclaw University of Science and Technology (Poland) used mPEG-PCL (AK074) and mPEG-PLA (AK084) from PolySciTech (www.polyscitech.com) to conduct advanced research on the nanoparticle structure. This holds promise to improve the use of these carriers in a variety of formulation approaches. Read more: Lamch, Łukasz, Roman Gancarz, Marta Tsirigotis-Maniecka, Izabela M. Moszyńska, Justyna Ciejka, and Kazimiera A. Wilk. "Studying the “Rigid–Flexible” Properties of Polymeric Micelle Core-Forming Segments with a Hydrophobic Phthalocyanine Probe Using NMR and UV Spectroscopy." Langmuir (2021). https://pubs.acs.org/doi/abs/10.1021/acs.langmuir.1c00328

“Abstract: The aim of the performed studies was to thoroughly examine the internal structure of self-assembled nanocarriers (i.e., polymeric micelles—PMs) by means of a hydrophobic phthalocyanine probe in order to identify the crucial features that are required to enhance the photoactive probe stability and reactivity. PMs of hydrophilic poly(ethylene glycol) and hydrophobic poly(ε-caprolactone) (PCL) or poly(d,l-lactide) (PDLLA) were fabricated and loaded with tetra tert-butyl zinc(II) phthalocyanine (ZnPc-t-but4), a multifunctional spectroscopic probe with a profound ability to generate singlet oxygen upon irradiation. The presence of subdomains, comprising “rigid” and “flexible” regions, in the studied block copolymers’ micelles as well as their interactions with the probe molecules, were assessed by various high-resolution NMR measurements [e.g., through-space magnetic interactions by the 1D NOE effect, pulsed field gradient spin-echo, and spin–lattice relaxation time (T1) techniques]. The studies of the impact of the core-type microenvironment on the ZnPc-t-but4 photochemical performance also included photobleaching and reactive oxygen species measurements. ZnPc-t-but4 molecules were found to exhibit spatial proximity effects with both (PCL and PDLLA) hydrophobic polymer chains and interact with both subdomains, which are characterized by different rigidities. It was deduced that the interfaces between particular subdomains constitute an optimal host space for probe molecules, especially in the context of photochemical stability, photoactivity (i.e., for significant enhancement of singlet oxygen generation rates), and aggregation prevention. The present contribution proves that the combination of an appropriate probe, high-resolution NMR techniques, and UV–vis spectroscopy enables one to gain complex information about the subtle structure of PMs essential for their application as nanocarriers for photoactive compounds, for example, in photodynamic therapy, nanotheranostics, combination therapy, or photocatalysis, where the micelles constitute the optimal microenvironment for the desired photoreactions.”

Thermogelling PLGA-PEG-PLGA from PolySciTech used in testing of cardiovascular healing post stenosis

Monday, March 29, 2021, 4:11 PM ET

Heart disease remains the most common cause of death world-wide. Although emplacement of cardiovascular stent can reduce damage from heart attack by maintaining blood flow there is the potential for restenosis as the tissue can in-grow into the stent structure and reclose the vessel. Recently, researchers at University of Virginia, University of Wisconsin, and Ohio State University used PLGA-PEG-PLGA (AK012) from PolySciTech (www.polyscitech.com) to create thermogels that provide for controlled delivery of a PLK4 inhibitor (centrinone-B) to enable study into the post-stent healing process. This research holds promise to improve outcomes from cardiovascular repair operations. Read more: Li, Jing, Go Urabe, Yitao Huang, Mengxue Zhang, Bowen Wang, Lynn Marcho, Hongtao Shen, K. Craig Kent, and Lian-Wang Guo. "A role for polo-like kinase 4 in vascular fibroblast cell-type transition." Basic to Translational Science 6, no. 3 (2021): 257-283. https://www.jacc.org/doi/abs/10.1016/j.jacbts.2020.12.015

“Highlights: PLK4, previously known as a centriole-associated factor, regulates the transcription factor activity of serum response factor. PLK4 inhibition blocks the profibrogenic cell state transition of vascular fibroblasts. PLK4’s activation and gene expression are regulated by PDGF receptor and epigenetic reader BRD4, respectively. Summary: Periadventitial administration of a PLK4 inhibitor mitigates vascular fibrosis. Polo-like kinase 4 (PLK4) is canonically known for its cytoplasmic function in centriole duplication. Here we show a noncanonical PLK4 function of regulating the transcription factor SRF’s nuclear activity and associated myofibroblast-like cell-type transition. In this context, we have further found that PLK4’s phosphorylation and transcription are respectively regulated by PDGF receptor and epigenetic factor BRD4. Furthermore, in vivo experiments suggest PLK4 inhibition as a potential approach to mitigating vascular fibrosis.”

Poloxamer-diacrylate from PolySciTech used in research on tough and adhesive hydrogels

Monday, March 29, 2021, 4:10 PM ET

The potential for use of adhesive hydrogels in medicine opens up a world in terms of surgical treatment and wound-repair options. For this, however, a hydrogel must be carefully designed which has the correct properties of biocompatibility and bioadhesion. Recently, researchers at Harvard University used poloxamer-diacrylate (AI146) from PolySciTech (www.polyscitech.com) to create strong, chemically crosslinked hydrogels and tested these for adhesion, degradation, and biocompatibility. This research holds promise to improve wound healing and traumatic injury repair in the future. Read more: Freedman, Benjamin R., Oktay Uzun, Nadja M. Maldonado Luna, Anna Rock, Charles Clifford, Emily Stoler, Gabrielle Östlund‐Sholars, Christopher Johnson, and David J. Mooney. "Degradable and Removable Tough Adhesive Hydrogels." Advanced Materials (2021): 2008553. https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.202008553

“Abstract: The development of tough adhesive hydrogels has enabled unprecedented adhesion to wet and moving tissue surfaces throughout the body, but they are typically composed of nondegradable components. Here, a family of degradable tough adhesive hydrogels containing ≈90% water by incorporating covalently networked degradable crosslinkers and hydrolyzable ionically crosslinked main‐chain polymers is developed. Mechanical toughness, adhesion, and degradation of these new formulations are tested in both accelerated in vitro conditions and up to 16 weeks in vivo. These degradable tough adhesives are engineered with equivalent mechanical and adhesive properties to nondegradable tough adhesives, capable of achieving stretches >20 times their initial length, fracture energies >6 kJ m−2, and adhesion energies >1000 J m−2. All degradable systems show complete degradation within 2 weeks under accelerated aging conditions in vitro and weeks to months in vivo depending on the degradable crosslinker selected. Excellent biocompatibility is observed for all groups after 1, 2, 4, 8, and 16 weeks of implantation, with minimal fibrous encapsulation and no signs of organ toxicity. On‐demand removal of the adhesive is achieved with treatment of chemical agents which do not cause damage to underlying skin tissue in mice. The broad versatility of this family of adhesives provides the foundation for numerous in vivo indications.”

PLGA-PEG-Mal used in research on intestinal permeation for oral bioavailability research

Monday, March 29, 2021, 4:09 PM ET

Oral bioavailability references the ability of a drug taken orally (either as a tablet or as a drinkable liquid) to be successfully taken into the bloodstream and circulate throughout the patient’s body. One classic example of oral bioavailability is acetylsalicylic acid (Aspirin) which has roughly 50% bioavailability. In the case of aspirin, the drug is readily available and cheaply manufactured so the incredibly unimaginative and yet wildly effective manner of dealing with 50% bioavailability was to double the dose given to the patient, knowing that about 50% of the drug will simply be lost without any benefit. Not all bioavailability problems can be addressed in such a simplistic manner as some molecules have little to no bioavailability or require carefully controlled dosing. In this case, understanding the exact bioavailability is critical and one of the most important rate-limiting steps of bioavailability is the ability for drugs to cross the intestinal mucosa layer into the blood stream. The small intestine is, metaphorically, the ‘Suez Canal’ of the human body and understanding uptake across the intestine is critical to bioavailability. Recently, researchers at University of Porto (Portugal), University of Oslo (Norway), Harvard Medical School, Massachusetts Institute of Technology, and Universitário de Ciências da Saúde (Portugal) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create particles decorated with neonatal Fc receptor to test their intestinal permeation model of specially prepared porcine mucosa. This research holds promise to improve oral delivery of medicines. Read more: Azevedo, Cláudia, Jan Terje Andersen, Giovanni Traverso, and Bruno Sarmento. "The potential of porcine ex vivo platform for intestinal permeability screening of FcRn-targeted drugs." European Journal of Pharmaceutics and Biopharmaceutics (2021). https://www.sciencedirect.com/science/article/abs/pii/S0939641121000746

“Highlights: FcRn is expressed across the gastrointestinal tract. FcRn expression in ex vivo porcine tissue is maintained up to 7 days in culture. Free KP present higher permeability in porcine ex vivo platform. The porcine ex vivo platform was revealed to be a potential model for the screening of FcRn-targeted oral drug formulations. Abstract: Conventionally, the intestinal permeability of drugs is evaluated using cell monolayer models that lack morphological, physiological and architectural features, as well as realistic neonatal Fc receptor (FcRn) expression. In addition, it is time-consuming, expensive and excessive to use a large number of mice for large-scale screening of FcRn-targeted candidates. For preclinical validation, it is critical to use suitable models that mimic the human intestine; the porcine ex vivo model is widely used for intestinal permeability studies, due to its physiological and anatomical similarities to humans. This study intended to analyze the potential to measure the intestinal permeability of FcRn-targeted substances using a porcine ex vivo platform, which is able to analyze 96 samples at the same time. In addition, the platform allows the screening of FcRn-targeting substances for transmucosal delivery, taking into consideration (cross-species) receptor-ligand binding kinetics. After analyzing the morphology of the porcine tissue, the FcRn expression across the gastrointestinal tract was verified. By studying the stomach, duodenum and jejunum, it was demonstrated that FcRn expression is maintained for up to 7 days. When evaluating the duodenum permeability of free engineered human albumin variants, it was shown that the variant with the mutation K573P (KP) is more efficiently transported. Given this, the porcine ex vivo platform was revealed to be a potential model for the screening of FcRn-targeted oral drug formulations.”

PLGA from PolySciTech used in development of vaccine to protect against heart disease

Wednesday, March 24, 2021, 9:58 AM ET

Heart disease has been the number one cause of death globally for a long time. Through the use of vaccines and related technologies, humans have the ability to prime and adjust the human immune system to leverage this powerful agent to effect changes within the body. One novel approach is to use this system to reduce arterial blockage and heart disease. Researchers at University of California-San Diego used PLGA (AP041) from PolySciTech (www.polyscitech.com) to create time-delayed antigen release systems to create a vaccine against cardiovascular disease by targeting the immune system against cholesterol-promoting proteins. This holds promise to provide for therapy against heart disease which is currently the most common cause of death. Read more: Ortega‐Rivera, Oscar A., Jonathan K. Pokorski, and Nicole F. Steinmetz. "A Single‐Dose, Implant‐Based, Trivalent Virus‐like Particle Vaccine against “Cholesterol Checkpoint” Proteins." Advanced Therapeutics: 2100014. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202100014

“Cardiovascular disease is the number one cause of death globally. Lowering cholesterol levels in plasma is the mainstay therapy; however lifelong treatment and adverse effects call for improved therapeutic interventions. A trivalent vaccine candidate targeting proprotein convertase subtilisin/kexin-9 (PCSK9), apolipoprotein B (ApoB), and cholesteryl ester transfer protein (CETP) is developed. Vaccine candidates are developed using bacteriophage Q𝜷-based virus-like particles (VLPs) displaying antigens of PCKS9, ApoB, and CETP, respectively. Vaccine candidate mixtures are formulated as slow-release PLGA:VLP implants using hot-melt extrusion. The delivery of the trivalent vaccine candidate via the implant produced antibodies against the cholesterol checkpoint proteins at levels comparable to a three-dose injection schedule with soluble mixtures. The reduction in PCSK9 and ApoB levels in plasma, inhibition of CETP (in vitro), and total plasma cholesterol decrease is achieved. Altogether, a platform technology for a single-dose multi-agent proteins is presented.”

PLGA-PEG-COOH from PolySciTech used in development of ultrasound-triggered delivery of miRNA/Gene Therapy for treatment of cancer

Tuesday, March 16, 2021, 10:54 AM ET

The delivery of genetic materials, RNA/DNA, to cells holds potential for the treatment of several disease states. That being said, getting these materials into the area of action is not a trivial task as endogenous RNAse and DNAse enzymes will often break them down as well as permeation across various membranes is not good. Recently researchers at Stanford University and Bracco Suisse SA use PLGA-PEG-COOH (AI034) from PolySciTech (www.polyscitech.com) to create ultrasound-responsive PLGA-PEG-PEI nanoparticles to deliver RNA/Gene therapy materials to cancer cells as a treatment regimen. This research holds promise to improve therapies against cancer. Read more: Kumar, Sukumar Uday, Huaijun Wang, Arsenii V. Telichko, Arutselvan Natarajan, Thierry Bettinger, Samir Cherkaoui, Tarik F. Massoud, Jeremy J. Dahl, and Ramasamy Paulmurugan. "Ultrasound Triggered Co‐Delivery of Therapeutic MicroRNAs and a Triple Suicide Gene Therapy Vector by Using Biocompatible Polymer Nanoparticles for Improved Cancer Therapy in Mouse Models." Advanced Therapeutics: 2000197. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202000197

“Microbubbles (MBs) exhibit cavitation upon exposure to ultrasound (US), which creates opportunities to adopt them in new therapeutic approaches. The present study reports an efficient, translatable approach to precisely control the spaciotemporal delivery of therapeutic microRNAs (AmiR‐21 and miR‐100) and TK‐p53‐NTR triple therapeutic gene, co‐loaded in PLGA‐PEG‐PEI polymer nanoparticles (NPs) to tumor models of triple negative breast cancer (TNBC) and hepatocellular carcinoma (HCC) using US‐mediated targeted destruction of BR38 MBs. PLGA‐PEG‐PEI conjugated triblock co‐polymer NPs are synthesized and characterized for their physicochemical properties, and optimized for co‐loading of miRNAs and TK‐p53‐NTR. Quantitative in vivo imaging and ex vivo tissue analysis of 4T1 (TNBC) subcutaneous tumors in BALB/c mice reveal 19 ± 0.5% (p < 0.01) increase in delivery of miRNAs, and 48 ± 1.79% (p < 0.001) increase in delivery of TK‐p53‐NTR upon US treatment, which results to 48 ± 6.98% (p < 0.01) reduction in tumor growth as compared to contralateral tumors without US. This significantly increases the survival rate of animals as compared to pDNA control group. Similar treatment effects are observed in both TNBC and HCC tumor models. This novel combined therapeutic approach, entailing both miRNAs and suicide gene therapy has strong potential for future applications in cancer therapy.”

PEG-PLGA from PolySciTech used in research on microfluidic nanoparticle preparation

Wednesday, March 10, 2021, 10:07 AM ET

There are many different methods available by which nanoparticles can be formulated. One method is to use microfluidic systems to create the particles under carefully controlled conditions. Recently, researchers at The University of Queensland (Australia) used mPEG-PLGA (AK026) from PolySciTech (www.polyscitech.com) to research nanoprecipitation methods to create drug-loaded nanoparticles. This research holds promise to provide for improved nanoparticle manufacturing capabilities. Read more: Li, Wei, Qiaoli Chen, Thejus Baby, Song Jin, Yun Liu, Guangze Yang, and Chun-Xia Zhao. "Insight into drug encapsulation in polymeric nanoparticles using microfluidic nanoprecipitation." Chemical Engineering Science 235 (2021): 116468. https://www.sciencedirect.com/science/article/pii/S0009250921000336

“Highlights: A combined computational fluid dynamics (CFD) and experimental approach to illustrate microfluidic nanoprecipitation. Mixing times of a polymer and a drug are determined using a CFD method. Drug loading is dependent on the mixing time of the polymer and drug. The precipitation time of polymer and drug should be matched for drug encapsulation. Abstract: Synthesis of polymeric nanoparticles (NPs) through self-assembly of di-block copolymers have attracted substantial interest in the past decades for drug delivery and controlled release. Microfluidics offers a facile approach for making such NPs and drug encapsulation. However, a fundamental understanding of the drug encapsulation process is lacking. In this paper, we report a combined computational fluid dynamics (CFD) and experimental approach to illustrate the fundamental principle that governs the encapsulation of a drug in polymeric NPs through microfluidic nanoprecipitation. Taking a drug curcumin and a polymer poly (ethylene glycol)-block-poly (d, l-lactide-co-glycolide) (PEG-PLGA) as a model system, we demonstrated the different precipitation times of curcumin and PEG-PLGA as well as their mixing times in the microfluidic device. The big difference in their mixing times led to very low drug loading. This study provides a new perspective in understanding and controlling the formation of drug-loaded polymeric NPs and offers a new design rule for selecting the right combinations of drugs, polymers, solvents, and devices. Keywords Microfluidic Self-assembly Nanoparticles mPEG-PLGA Polymer nanoparticles Nanoprecipitation Drug encapsulation”

PLGA from PolySciTech used in development of canine cancer vaccine

Wednesday, March 10, 2021, 10:06 AM ET

With the appropriate presentation of markers and adjuvents it is possible to induce the bodily immune systems to recognize cancer as non-selve and attack it. This immunotherapy approach can potentially allow for prevention or treatment of cancer. Recently, researchers at Washington State University used PLGA (AP054) from PolySciTech (www.polyscitech.com) to create PLGA nanoparticles loaded with antigens from lysed cancer cells. This research holds promise to improve therapies against cancer in many species. Read more: Eren, Meaghan Veronica, Julianne Hwang, Janean Fidel, Rance Sellon, and Cleverson de Souza. "Preliminary Evaluation of an Autologous Dendritic Cell Vaccine Using Nanoparticle Technology for the Treatment of Canine Malignant Melanoma." American Journal of Biomedical and Life Sciences 9, no. 1 (2021): 84-96. http://www.biomedlife.org/article/655/10.11648.j.ajbls.20210901.21)

“Abstract: Canine malignant melanoma is an aggressive neoplasm that carries a poor prognosis due to its minimal responsiveness to traditional therapy protocols, particularly if the oral cavity, mucocutaneous junctions, or subungual sites are involved. This proof-of-concept study evaluated a prototype autologous dendritic cell vaccine using poly-lactic-co-glycolic (PLGA) nanoparticles containing antigens from patient-derived whole tumor lysate and the adjuvant monophosphoryl lipid A in five canines with stages III-IV malignant melanoma. Nanoparticle constructs biochemical characterization; encapsulation efficiency and kinetic release studies were determined. Our results showed that tumor antigens were successfully incorporated in the PLGA/monophosphoryl lipid A nanoparticle constructs. Additional in vitro experiments showed that the PLGA/monophosphoryl lipid A nanoparticle constructs effectively activated autologous dendritic cells, and generated a greater than twofold increase in the release of the pro-immune cytokine IFN-γ. No significant adverse effects were observed in any of the patients following intradermal vaccination, and flow cytometry of whole blood revealed increased CD4:CD8 T lymphocyte ratios by the completion of the study. These results suggest that a dendritic cell vaccine utilizing PLGA/monophosphoryl lipid A nanoparticle technology could potentially initiate an adaptive immune response and is safe to administer to canine patients. Further in vivo studies with a larger cohort of patients are warranted. Keywords Melanoma, Nanoparticles, Dendritic Cells, Adaptive Immunity, Cancer Vaccine”

PLGAs from PolySciTech used in development of periodontal-simulating test chamber for drug release assays

Monday, March 1, 2021, 2:14 PM ET

PLGA microparticles are routinely used for delivery of long-acting injectable drugs. For these formulations, the drug is encapsulated in the biodegradable PLGA and elutes out slowly due to drug diffusion and polymer degradation. A rather critical question is at what rate the drug elutes out and this depends on the formulation parameters and polymer type used. In order to test this, however, a system must be designed which replicates the important components of the human body and allows for the drug elution to be measured using HPLC or other analytical techniques. Arestin is a unique formulation in that it is designed to go into the periodontal pocket (gumline) around teeth and slowly release antibacterial agents for localized activity. Due to the location of this formulation (as opposed to typical intra-muscular injection sites in the shoulder or buttocks used for conventional LAR formulations) it has a rather unique local environment in the gumline which is difficult to replicate. Recently, researchers at University of Pittsburgh, Magee-Women’s Research Institute, Qrono Inc, and Food and Drug Administration used multiple PLGAs (AP125, AP037, AP081, AP030, AP150) purchased from PolySciTech (www.polyscitech.com) to develop a variety of PLGA-minocycline formulations and test these out on a novel flow-release chamber used to represent the periodontal pocket release. This research holds promise to improve analytical techniques applied for testing long-acting injectable formulations. Read more: Patel, Sravan Kumar, Ashlee C. Greene, Stuti M. Desai, Sam Rothstein, Iman Taj Basha, James Scott MacPherson, Yan Wang et al. "Biorelevant and screening dissolution methods for minocycline hydrochloride microspheres intended for periodontal administration." International Journal of Pharmaceutics 596 (2021): 120261. https://www.sciencedirect.com/science/article/pii/S037851732100065X

“Abstract: Currently, there is no compendial-level method to assess dissolution of particulate systems administered in the periodontal pocket. This work seeks to develop dissolution methods for extended release poly(lactic-co-glycolic acid) (PLGA) microspheres applied in the periodontal pocket. Arestin®, PLGA microspheres containing minocycline hydrochloride (MIN), is indicated for reduction of pocket depth in adult periodontitis. Utilizing Arestin® as a model product, two dissolution methods were developed: a dialysis set-up using USP apparatus 4 and a novel apparatus fabricated to simulate in vivo environment of the periodontal pocket. In the biorelevant method, the microspheres were dispersed in 250 μL of simulated gingival crevicular fluid (sGCF) which was enclosed in a custom-made dialysis enclosure. sGCF was continuously delivered to the device at a biorelevant flow rate and was collected daily for drug content analysis using UPLC. Both methods could discriminate release characteristics of a panel of MIN-loaded PLGA microspheres that differed in composition and process conditions. A mechanistic model was developed, which satisfactorily explained the release profiles observed using both dissolution methods. The developed methods may have the potential to be used as routine quality control tools to ensure batch-to-batch consistency and to support evaluation of bioequivalence for periodontal microspheres. Keywords: Dissolution PLGA Minocycline Biorelevant Microspheres Periodontal Modeling”

PLGA-PEG-Biotin from PolySciTech used in development of multifunctional Janus nanoparticles

Wednesday, February 24, 2021, 2:16 PM ET

In ancient Roman mythology, Janus is the god of doors and gates. He is depicted as having two faces because he is both looking outward and inward at the same time. Having a dual nature is a property which would be desirable for nanoparticles as this will enable the ability for more complicated functions. Recently, researchers at University of California San Francisco used PLGA-PEG-Biotin (AI167) and PLGA (AP061) to create long, tubular nanoparticles with different functionalities based on orientation. This research holds promise to allow more complicated nanotechnology operations by having higher control over the shape and geospatial considerations of nanoparticles. Read more: Finbloom, Joel A., Yiqi Cao, and Tejal A. Desai. "Bioinspired Polymeric High Aspect Ratio Particles with Asymmetric Janus Functionalities." Advanced NanoBiomed Research: 2000057. https://onlinelibrary.wiley.com/doi/abs/10.1002/anbr.202000057

“Abstract: Polymeric particles with intricate morphologies and properties have been developed based on bioinspired designs for applications in regenerative medicine, tissue engineering, and drug delivery. However, the fabrication of particles with asymmetric functionalities remains a challenge. Janus polymeric particles are an emerging class of material with asymmetric functionalities; however, they are predominantly spherical in morphology, made from non‐biocompatible materials, and made using specialized fabrication techniques. We therefore set out to fabricate nonspherical Janus particles inspired by high aspect ratio filamentous bacteriophage using polycaprolactone polymers and standard methods. Janus high aspect ratio particles (J‐HARPs) were fabricated with a nanotemplating technique to create branching morphologies selectively at one edge of the particle. J‐HARPs were fabricated with maleimide handles and modified with biomolecules such as proteins and biotin. Regioselective modification was observed at the tips of J‐HARPs, likely owing to the increased surface area of the branching regions. Biotinylated J‐HARPs demonstrated cancer cell biotin receptor targeting, as well as directional crosslinking with spherical particles via biotin‐streptavidin interactions. Lastly, maleimide J‐HARPs were functionalized during templating to contain amines exclusively at the branching regions and were dual‐labeled orthogonally, demonstrating spatially separated bioconjugation. Thus, J‐HARPs represent a new class of bioinspired Janus material with excellent regional control over biofunctionalization.”

PLA-PEG-PLA diacrylate from PolySciTech Used in testing of crosslinked rituximab-loaded nanoparticles for treatment of non-Hodgkin’s lymphoma in novel mouse model

Monday, February 22, 2021, 2:12 PM ET

Replicating the human body conditions in another animal is not a trivial task however necessary for creating therapies against complex diseases such as cancer which can not be replicated using cell-cultures or other benchtop techniques. Recently, researchers at University of California Los Angeles and University of Alabama used PLA-PEG-PLA-diacrylate (AI102) from PolySciTech (www.polyscitech.com) to form crosslinked particles loaded with Rituximab as a cancer therapy and tested these against a novel mouse model. This research holds promise to improve both therapies and testing of those therapies for treatment of cancer. Read more: Wen, Jing, Lan Wang, Jie Ren, Emiko Kranz, Shilin Chen, Di Wu, Toshio Kanazawa, Irvin Chen, Yunfeng Lu, and Masakazu Kamata. "Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model." Journal for ImmunoTherapy of Cancer 9, no. 2 (2021): e001524. https://jitc.bmj.com/content/9/2/e001524.abstract

“Abstract: Background Despite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally used as a model for testing cancer-targeting mAbs. However, this strain lacks several factors necessary to fully support antibody-mediated effector functions—including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity (CDC)—due to the absence of immune cells as well as a mutation in the Hc gene, which is needed for a functional complement system. Methods: We have developed a humanized mouse model using a novel NSG strain, NOD.Cg−Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG−Hc1), which contains the corrected mutation in the Hc gene to support CDC in addition to other mechanisms endowed by humanization. With this model, we reevaluated the anticancer efficacies of nanoencapsulated rituximab after xenograft of the human Burkitt lymphoma cell line 2F7-BR44. Results: As expected, xenografted humanized NSG−Hc1 mice supported superior lymphoma clearance of native rituximab compared with the parental NSG strain. Nanoencapsulated rituximab with CXCL13 conjugation as a targeting ligand for lymphomas further enhanced antilymphoma activity in NSG−Hc1 mice and, more importantly, mediated antilymphoma cellular responses. Conclusions: These results indicate that NSG−Hc1 mice can serve as a feasible model for both studying antitumor treatment using cancer targeting as well as understanding induction mechanisms of antitumor cellular immune response.”

PLGA from PolySciTech used in development of HER2-targeted doxycycline-based nanoparticle therapy for breast cancer.

Wednesday, February 17, 2021, 2:35 PM ET

With the exclusion of very specific types of breast cancer, such as triple-negative breast cancer lines, most breast cancers present human epidermal growth factor receptor 2 (HER2) marker on their surface. The use of compounds which selectively attach to this marker (such as Trastuzumab (TZB)) allows for delivery of materials specifically to the tumor cells to treat the cancer. Recently, researchers at Universidad de Guadalajara, Universidad de Sonora (Mexico), Universidad Tecnológica Metropolitana, Universidad de Chile, and Advanced Center for Chronic Diseases (Chile) used PLGA (AP081) from PolySciTech (www.polyscitech.com) to create doxycycline-loaded nanoparticles coated with HER2 targeting ligand as a treatment for breast cancer. This research holds promise to improve therapies against this potentially fatal disease in the future. Read more: Escareño, Noé, Natalia Hassan, Marcelo J. Kogan, Josué Juárez, Antonio Topete, and Adrián Daneri-Navarro. "Microfluidics-Assisted Conjugation of Chitosan-Coated Polymeric Nanoparticles with Antibodies: Significance in Drug Release, Uptake, and Cytotoxicity in Breast Cancer Cells." Journal of Colloid and Interface Science (2021). https://www.sciencedirect.com/science/article/pii/S0021979721001648

“Nanoparticle-based drug delivery systems, in combination with high-affinity disease-specific targeting ligands, provide a sophisticated landscape in cancer theranostics. Due to their high diversity and specificity to target cells, antibodies are extensively used to provide bioactivity to a plethora of nanoparticulate systems. However, controlled and reproducible assembly of nanoparticles (NPs) with these targeting ligands remains a challenge. In this context, determinants such as ligand density and orientation, play a significant role in antibody bioactivity; nevertheless, these factors are complicated to control in traditional bulk labeling methods. Here, we propose a microfluidic-assisted methodology using a PDMS (polydimethylsiloxane) Y-shaped microreactor for the covalent conjugation of Trastuzumab (TZB), a recombinant antibody targeting HER2 (human epidermal growth factor receptor 2) to doxorubicin-loaded PLGA/Chitosan NPs (PLGA/DOX/Ch NPs) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysulfosuccinimide (sNHS) mediated bioconjugation reactions. Our labeling approach led to smaller and less disperse nanoparticle-antibody conjugates providing differential performance when compared to bulk-labeled NPs in terms of drug release kinetics (fitted and analyzed with DDSolver), cell uptake/labeling, and cytotoxic activity on HER2+ breast cancer cells in vitro. By controlling NP-antibody interactions in a laminar regime, we managed to optimize NP labeling with antibodies resulting in ordered coronas with optimal orientation and density for bioactivity, providing a cheap and reproducible, one-step method for labeling NPs with globular targeting moieties. Keywords: Microfluidics polymeric nanoparticles PLGA nanoparticles chitosan antibody antibody-nanoparticle conjugate”

Weather Closure 2-16-2021

Tuesday, February 16, 2021, 6:23 AM ET

Due to extreme winter weather, Akina Inc. is closed for operations 2-16-2021. Orders placed at this time will be filled the next available business day.

Weather Advisory 2/15/2021

Monday, February 15, 2021, 4:27 PM ET

Weather Advisory 2/15/2021: Due to severe winter weather, Akina Inc. will be operating at limited capacity and will be unable to ship orders placed today and tomorrow. Orders placed during this time will be sent out at next available business day.

PLGA from PolySciTech Used in development of antibacterial surfaces for surgical implants to prevent infection

Monday, February 15, 2021, 1:52 PM ET

A common problem with surgical interventions is the potential for bacterial infections to grow and spread particularly along the surfaces of implanted materials. In addition to conventional asceptic surgical practices the use of surfaces which release antibiotics and have antimicrobial properties can prevent such infections. Recently, researchers at Università di Perugia (Italy) used PLGA (AP020) from PolySciTech (www.polyscitech.com) along with zirconium phosphate to produce polymeric composites which released antibacterial and other compounds to prevent infection. This research holds promise to reduce surgery-related infections. Read more: Pica, Monica, Nicla Messere, Tommaso Felicetti, Stefano Sabatini, Donatella Pietrella, and Morena Nocchetti. "Biofunctionalization of Poly (lactide-co-glycolic acid) Using Potent NorA Efflux Pump Inhibitors Immobilized on Nanometric Alpha-Zirconium Phosphate to Reduce Biofilm Formation." Materials 14, no. 3 (2021): 670. https://www.mdpi.com/982146

“Abstract: Polymeric composites, where bioactive species are immobilized on inorganic nanostructured matrix, have received considerable attention as surfaces able to reduce bacterial adherence, colonization, and biofilm formation in implanted medical devices. In this work, potent in-house S. aureus NorA efflux pump inhibitors (EPIs), belonging to the 2-phenylquinoline class, were immobilized on nanometric alpha-zirconium phosphate (ZrP) taking into advantage of acid-base or intercalation reactions. The ZrP/EPI were used as filler of poly(lactide-co-glycolic acid) (PLGA) to obtain film composites with a homogeneous distribution of the ZrP/EPI fillers. As reference, PLGA films loaded with ZrP intercalated with thioridazine (TZ), that is recognized as both a NorA and biofilm inhibitor, and with the antibiotic ciprofloxacin (CPX) were prepared. Composite films were characterized by X-ray diffraction, scanning electron microscopy, and thermogravimetric analysis. The ability of the composite films, containing ZrP/EPI, to inhibit biofilm formation was tested on Staphylococcus aureus ATCC 29213 and Staphylococcus epidermidis ATCC 12228, and it was compared with that of the composite loaded with ZrP/TZ. Finally, the antibacterial activity of CPX intercalated in ZrP was evaluated when used in combination with ZrP/EPI in the PLGA films. Keywords: zirconium phosphate; PLGA; Efflux pump inhibitors; biofilm inhibition; composites”

PEG-PLGA from PolySciTech used in development of dual-chemotherapy system for cancer treatment

Tuesday, February 9, 2021, 3:24 PM ET

The treatment of lung cancer often involves a combination of chemotherapy and radiation. While it can be effective, it also has a high toxicity profile. Preferential delivery of chemotherapeutics to the tumor while avoiding normal tissue would improve efficacy and lower toxicity. While this is challenging with conventional drug delivery technologies, nanotechnology offers a unique opportunity. Recently researchers at University of North Carolina at Chapel Hill, Westminster College, China Medical University, Peking Union Medical College, and University of Science and Technology of China used PEG-PLGA (AK029) from PolySciTech (www.polyscitech.com) to design nanoparticles that are loaded with cisplatin and etoposide. This research holds promise to provide for improved therapies against cancer. Read more: Zhang, Maofan, C. Tilden Hagan IV, Hayley Foley, Xi Tian, Feifei Yang, Kin Man Au, Yu Mi et al. "Co-delivery of Etoposide and Cisplatin in Dual Drug Loaded Nanoparticles Synergistically Improves Chemoradiotherapy in Non-Small Cell Lung Cancer Models." Acta Biomaterialia (2021). https://www.sciencedirect.com/science/article/pii/S1742706121000866

“Abstract: Chemoradiotherapy with cisplatin and etoposide is a curative management regimen for both small and non-small cell lung cancers. While the treatment regimen is effective, it also has a high toxicity profile. One potential strategy to improve the therapeutic ratio of chemoradiation is to utilize nanotherapeutics. Nanoparticle formulation of cisplatin and etoposide, however, is challenging due to the significant mismatch in chemical properties of cisplatin and etoposide. Herein we report the formulation of a polymeric nanoparticle formulation of cisplatin and etoposide using a prodrug approach. We synthesized a hydrophobic platinum prodrug, which was then co-delivered with etoposide using a nanoparticle. Using mouse models of lung cancer, we demonstrated that dual drug loaded nanoparticles are significantly more effective than small molecule chemotherapy in chemoradiotherapy. These results support further investigation of nanoparticle-based drug formulations of combination chemotherapies and the use of nanotherapeutics in chemoradiotherapy. Keywords: nanomedicine nanoparticle lung cancer chemoradiotherapy combination drug delivery”

PLGA-PEG-Mal From PolySciTech used to develop immunotherapy nanoparticles

Tuesday, February 9, 2021, 3:23 PM ET

Most treatments against cancer (radiation, chemotherapy, surgical removal) rely on destroying or removing the tumor tissue as part of the therapy directly. Immunotherapy is a different mechanism in which the immune system is effectively ‘trained’ (for lack of a better description) to recognize and attack the cancer. Recently, researchers at University of California San Fransisco (UCSF) used PLGA-PEG-Mal (AI053) from PolySciTech (www.polyscitech.com) to develop nanoparticles which bear a variety of markers on their outer surface that induce an immune reaction against cancer. This research holds promise to improve therapies against cancer. Read more: Levy, Elizabeth S., Ryan Chang, Colin R. Zamecnik, Miqdad O. Dhariwala, Lawrence Fong, and Tejal A. Desai. "Multi-Immune Agonist Nanoparticle Therapy Stimulates Type I Interferons to Activate Antigen-Presenting Cells and Induce Antigen-Specific Antitumor Immunity." Molecular Pharmaceutics (2021). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.0c00984

“Cancer immunity is mediated by a delicate orchestration between the innate and adaptive immune system both systemically and within the tumor microenvironment. Although several adaptive immunity molecular targets have been proven clinically efficacious, stand-alone innate immunity targeting agents have not been successful in the clinic. Here, we report a nanoparticle optimized for systemic administration that combines immune agonists for TLR9, STING, and RIG-I with a melanoma-specific peptide to induce antitumor immunity. These immune agonistic nanoparticles (iaNPs) significantly enhance the activation of antigen-presenting cells to orchestrate the development and response of melanoma-sensitized T-cells. iaNP treatment not only suppressed tumor growth in an orthotopic solid tumor model, but also significantly reduced tumor burden in a metastatic animal model. This combination biomaterial-based approach to coordinate innate and adaptive anticancer immunity provides further insights into the benefits of stimulating multiple activation pathways to promote tumor regression, while also offering an important platform to effectively and safely deliver combination immunotherapies for cancer. KEYWORDS: polymeric nanoparticles cancer immunotherapy innate immunity immunology”

Fluorescent PLA-CY5 from PolySciTech used in development of bioadhesive particles for skin-cancer treatment

Monday, February 8, 2021, 10:24 AM ET

Skin cancer is an extremely common form of cancer which can spread and become very dangerous. There are relatively few treatment options for it other than surgical removal. Recently, researchers at Yale University used polylactide (PLA)-CY5 conjugate (AV032) from PolySciTech (www.polyscitech.com) to create nanoparticles that could be tracked under microscopy. These particles were used as part of a therapy option for skin cancer and hold promise to improve therapies against this disease. Read more: Hu, Jamie K., Hee-Won Suh, Munibah Qureshi, Julia M. Lewis, Sharon Yaqoob, Zoe M. Moscato, Sofia Griff et al. "Nonsurgical treatment of skin cancer with local delivery of bioadhesive nanoparticles." Proceedings of the National Academy of Sciences 118, no. 7 (2021). https://www.pnas.org/content/118/7/e2020575118.short

“Significance: One in five individuals in the United States will develop skin cancer over the course of a lifetime, and nonsurgical options are limited. To address this, we developed a bioadhesive nanoparticle (BNP) treatment for long-lasting local drug delivery. Incorporation of the topoisomerase inhibitor camptothecin (CPT) into BNPs enhanced tumor cell uptake, bioadhesion within the tumor microenvironment, and prolonged intratumoral drug retention. Therefore, we investigated BNPs encapsulating CPT as a local, nonsurgical treatment for nodular squamous cell carcinoma (SCC) skin cancers in a mouse model. BNP-CPT treatment facilitated tumor destruction and resolution, and was compatible with local immunotherapy. These findings suggest that BNP delivery of antitumor agents may provide opportunities for nonsurgical treatment of nodular skin cancers like SCC. Abstract: Keratinocyte-derived carcinomas, including squamous cell carcinoma (SCC), comprise the most common malignancies. Surgical excision is the therapeutic standard but is not always clinically feasible, and currently available alternatives are limited to superficial tumors. To address the need for a nonsurgical treatment for nodular skin cancers like SCC, we developed a bioadhesive nanoparticle (BNP) drug delivery system composed of biodegradable polymer, poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG), encapsulating camptothecin (CPT). Nanoparticles (NPs) of PLA-HPG are nonadhesive NPs (NNPs), which are stealthy in their native state, but we have previously shown that conversion of the vicinal diols of HPG to aldehydes conferred NPs the ability to form strong covalent bonds with amine-rich surfaces. Herein, we show that these BNPs have significantly enhanced binding to SCC tumor cell surfaces and matrix proteins, thereby significantly enhancing the therapeutic efficacy of intratumoral drug delivery. Tumor injection of BNP-CPT resulted in tumor retention of CPT at ∼50% at 10 d postinjection, while CPT was undetectable in NNP-CPT or free (intralipid) CPT-injected tumors at that time. BNP-CPT also significantly reduced tumor burden, with a portion (∼20%) of BNP-CPT–treated established tumors showing histologic cure. Larger, more fully established PDV SCC tumors treated with a combination of BNP-CPT and immunostimulating CpG oligodeoxynucleotides exhibited enhanced survival relative to controls, revealing the potential for BNP delivery to be used along with local tumor immunotherapy. Taken together, these results indicate that percutaneous delivery of a chemotherapeutic agent via BNPs, with or without adjuvant immunostimulation, represents a viable, nonsurgical alternative for treating cutaneous malignancy. Keywords: squamous cell carcinoma drug delivery nanoparticle chemotherapy immunotherapy”

Fluorescent PLGA-FITC from PolySciTech used in development of single-dose HPV vaccine.

Wednesday, February 3, 2021, 10:51 AM ET

HPV is a common STD which leads to cervical cancer. Requiring multiple doses for vaccination often leads to poor compliance and efficacy. Recently, researchers at University of California San Diego used PLGA-FITC (AV002) as part of developing a single-dose HPV vaccine. The PLGA-FITC was used in critical studies to determine localization and fate of the delivery system as this fluorescent polymer can be easily observed under microscope as it glows brightly when illuminated with ultraviolet light. This research holds promise to reduce the incidence of cervical cancer by preventing HPV spread. Read more: Shao, Shuai, Oscar A Ortega-Rivera, Sayoni Ray, Jonathan K Pokorski, and Nicole F Steinmetz. "A Scalable Manufacturing Approach to Single Dose Vaccination against HPV." Vaccines 9, no. 1 (2021): 66. https://www.mdpi.com/966550

“Human papillomavirus (HPV) is a globally prevalent sexually-transmitted pathogen, responsible for most cases of cervical cancer. HPV vaccination rates remain suboptimal, partly due to the need for multiple doses, leading to a lack of compliance and incomplete protection. To address the drawbacks of current HPV vaccines, we used a scalable manufacturing process to prepare implantable polymer–protein blends for single-administration with sustained delivery. Peptide epitopes from HPV16 capsid protein L2 were conjugated to the virus-like particles derived from bacteriophage Qβ, to enhance their immunogenicity. The HPV-Qβ particles were then encapsulated into poly(lactic-co-glycolic acid) (PLGA) implants, using a benchtop melt-processing system. The implants facilitated the slow and sustained release of HPV-Qβ particles without the loss of nanoparticle integrity, during high temperature melt processing. Mice vaccinated with the implants generated IgG titers comparable to the traditional soluble injections and achieved protection in a pseudovirus neutralization assay. HPV-Qβ implants offer a new vaccination platform; because the melt-processing is so versatile, the technology offers the opportunity for massive upscale into any geometric form factor. Notably, microneedle patches would allow for self-administration in the absence of a healthcare professional, within the developing world. The Qβ technology is highly adaptable, allowing the production of vaccine candidates and their delivery devices for multiple strains or types of viruses. Keywords: HPV vaccine candidate; L2 protein; Qβ; virus-like particles (VLPs); PLGA implants; vaccine delivery device; hot melt extrusion”

PLGA from PolySciTech used in development of dual-drug nanotherapy against Non-small cell lung cancer

Wednesday, February 3, 2021, 10:50 AM ET

Non-small cell lung cancer (NSCLC) is a common type of lung cancer which affects millions worldwide. It remains very difficult to treat as commonly applied drugs often lead to drug resistant strains of the cancer which require even more aggressive therapies. Recently, researchers at St. John's University and Keck Graduate Institute used PLGA’s (AP040, AP045, AP036) from PolySciTech (www.polyscitech.com) as part of their development of a dual-drug nanoparticle carrier assembly. They found the combination of Quinacrine and Erlotinib in nanoparticle formulations is more effective than either drug as these drugs work together against the cancer. This research holds promise to improve therapy against Non-small cell lung cancer (NSCLC). Read more: Kulkarni, Nishant S., Bhuvaneshwar Vaidya, and Vivek Gupta. "Nano-synergistic Combination of Erlotinib and Quinacrine for Non-Small Cell Lung Cancer (NSCLC) Therapeutics–Evaluation in Biologically Relevant In-vitro Models." Materials Science and Engineering: C (2021): 111891. https://www.sciencedirect.com/science/article/pii/S0928493121000291

“Highlights: Proof-of-concept study to ascertain the potential of Erlotinib and Quinacrine to work synergistically against NSCLC. Sensitization of cancer cells still remains a viable technique to enhance synergistic potential of a combination therapy. Use of nanoformulations can effectively enhance the synergistic potential of erlo-quin combinatorial therapy. Use of Bio-relevant 3D and 5D in-vitro tumor models for effectively testing therapy for Non-small cell lung cancer (NSCLC). Abstract: Non-small cell lung cancer (NSCLC), pre-dominant subtype of lung cancer, is a global disorder affecting millions worldwide. One of the early treatments for NSCLC was use of a first-generation tyrosine kinase inhibitor, Erlotinib (Erlo). However, chronic exposure to Erlo led to development of acquired drug resistance (ADR) in NSCLC, limiting the clinical use of Erlo. A potential approach to overcome development of ADR is a multi-drug therapy. It has been previously reported that Erlo and Quinacrine (QA), an anti-malarial drug, can work synergistically to inhibit tumor progression in NSCLC. However, the combination failed at clinical stages, citing lack of efficacy. In this study, an effort has been made to improve the efficacy of Erlo-QA combination via development of nanoformulations, known to enhance therapeutic efficacy of potent chemotherapies. Synergy between Erlo and QA was measured via estimating the combination indices (CI). It was seen that established combination of nanoformulations (CI: 0.25) had better synergy than plain drug solutions (CI: 0.85) in combination. Following extensive in-vitro testing, data were simulated in biologically relevant 3D tumor models. Two tumor models were developed for extensive in-vitro testing, 3D-Spheroids grown in ultra-low attachment culture plates for efficacy evaluation and a 5D-spheroid model in 5D-sphericalplate with capability of growing 750 spheroids/well for protein expression analysis. Extensive studies on these models revealed that combination of Erlo and QA nanoformulations overall had a better effect in terms of synergy enhancement as compared to plain drug combination. Further, effect of combinatorial therapy on molecular markers was evaluated on 5D-Sphericalplate leading to similar effects on synergy enhancement. Results from present study suggests that combination of nanoformulations can improve the synergy between Erlo and QA while reducing the overall therapeutic dose.”

PEG-Chitosan from PolySciTech used in development of novel oral-delivery system

Monday, February 1, 2021, 3:12 PM ET

Oral dosage with pills, capsules, liquids or other formulations is significantly more convenient and less painful for the patient than parental injections. However, several drugs do not have good permeation across the intestinal mucosa or are destroyed in the stomach which limits their ability to be administered orally. Recently, researchers at Hacettepe University (Turkey) and University of Aalborg (Denmark) used PEG-Chitosan from PolySciTech (www.polyscitech.com) to create nanosystems for delivery of Aprepitant which is used to reduce nausea during chemotherapy. This research holds promise to improve the ease and convenience of medicines by enabling oral route. Read more: Erdoğar, Nazlı, Safiye Akkın, Thorbjorn T. Nielsen, Esin Özçelebi, Batuhan Erdoğdu, Emirhan Nemutlu, Alper B. İskit, and Erem Bilensoy. "Development of oral aprepitant-loaded chitosan–polyethylene glycol-coated cyclodextrin nanocapsules: formulation, characterization, and pharmacokinetic evaluation." Journal of Pharmaceutical Investigation (2021): 1-14. https://link.springer.com/article/10.1007/s40005-020-00511-x

“Abstract: Aprepitant (APRT), a selective neurokinin 1 antagonist, is clinically used in the prevention of acute and delayed chemotherapy-induced nausea and vomiting. The low solubility of APRT, which limits its oral bioavailability, is overcome by nanonization. This study aimed to design and evaluate novel in vitro and in vivo chitosan (CS)–polyethylene glycol (PEG)-coated cyclodextrin (CD) nanoparticles and nanocapsules to enhance the solubility and oral bioavailability of APRT. Methods: A novel amphiphilic CD derivative with alkyl chains of 9 carbons (ACD-C9) was synthesized to form nanoparticles and nanocapsules by using nanoprecipitation. The nanocarriers were coated with the CS–PEG conjugate to increase their biological interaction with cell membranes via the positive charge and penetration-enhancer properties of CS. The nanosystems were evaluated for particle size, surface charge, drug loading, imaging, release, cell culture, and oral bioavailability in an animal model. Results: The CS–PEG-coated nanosystems had particle size of 400–550 nm, a narrow polydispersity index, positive zeta potential, and favorable drug loading (55 and 93% for nanoparticles and nanocapsules, respectively). Sustained release was observed within 24 h. Blank nanoparticles and nanocapsules were non-cytotoxic against the L929 cell line. The intestinal permeability of the nanocarriers was 2–threefold (2-3 fold) higher than that of the drug solution, and the nanocapsules afforded the highest APRT permeability through Caco-2 cells. Oral bioavailability studies in rats revealed comparable degree of drug absorption between nanocapsules and commercial APRT products. Conclusion: Oral ACD-C9 nanocapsules have the potential for the treatment of chemotherapy-induced nausea and vomiting.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.24456095695496 seconds)


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