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 from PolySciTech used in development of microelectrode array for non-opioid pain management

Tuesday, October 5, 2021, 10:55 AM ET

Current pain management strategies typically rely on opioid medications which have a high propensity to lead to addiction. Opioid addiction has become a world-wide societal problem in recent years requiring research into opioid-free pain relief strategies. Recently, researchers at University of Washington used mPEG-PLGA (Cat# AK106) and PLGA (Cat# AP045) from PolySciTech (www.polyscitech.com) to create curcumin-loaded nanoparticles as part of development of nanoparticle loaded microelectrode array for pain management. This research holds promise to improve pain management strategies in the future. Read more: Xu, Nuo. "Nanoparticle loaded implantable flexible microelectrode arrays for pain management after spinal cord surgery." PhD diss., University of Washington, 2021. https://search.proquest.com/openview/530e9f32e470658b868b55aabf7b6312/1?pq-origsite=gscholar&cbl=18750&diss=y

“Abstract: The health care system currently faces significant burden with abuse of opioids and an unmet market need for pain management after surgery and injury. A drug delivery device that can improve drug delivery efficiency, increase drug duration of action, and deliver anesthetics topically with low toxicity is needed. Implantable flexible microelectrode arrays are widely used after spinal cord injury for pain mainagement, but they have limitations in improving the solubility, bioavailability, and permeability of drug. Biodegradable polymeric nanoparticles have highly tailorable physicochemical properties, and with incorporation on microelectrode arrays (MEAs), may increase the physical and chemical properties of therapeutic agents such as permeability, solubility and bioavailability. However, drug-loaded biodegradable nanoparticle-polypyrrole coated MEA for drug delivery has not been reported in literature. Therefore, we investigate the use of biodegradable nanoparticles for controlled release of bupivacaine hydrochloride from MAEs for pain management following spinal cord surgery. Bupivacaine hydrochloride, a commonly used FDA-approved anesthetic, is chosen as the model drug due to its nerve block and anti-inflammatory effects. This work starts with the exploration of the relationship between the formulation parameters of biodegradable nanoparticles and their physicochemical properties. Then, the bupivacaine hydrochloride loaded nanoparticles are formulated, and the drug loading of the nanoparticles is explored through iterating formulation parameters. Thereafter, nanoparticles with different surface charges are loaded on the MAEs to determine the relationship between the surface charge of nanoparticles and the release behavior of these nanoparticles. Finally, the release behavior of the nanoparticles from the MAEs is used as a guide to further optimize the bupivacaine hydrochloride loaded nanoparticle formulation.”

PLA from PolySciTech used in development of Doxycycline/miR-21i co-delivery nanoparticle for cancer treatment

Monday, September 27, 2021, 3:00 PM ET

One potential method for treatment of cancer is by reducing the amount of microRNA that the cancer can produce in addition to conventional chemotherapy. Recently, researchers at University of Cincinnati used PLA (AP128) from PolySciTech to create multi-drug loaded nanoparticles. This treatment holds promise to improve therapy against cancer. Rear more: Sriram, Vishnu, and Joo-Youp Lee. "Calcium Phosphate-Polymeric Nanoparticle System for Co-delivery of microRNA-21 Inhibitor and Doxorubicin." Colloids and Surfaces B: Biointerfaces (2021): 112061. https://www.sciencedirect.com/science/article/abs/pii/S0927776521005051

“Highlights: NPs successfully achieved sequential delivery of miR-21 inhibitor followed by Dox. NPs delivered miR-21 inhibitor to the cytoplasm through endosomal escape. NPs downregulated miR-21 levels and upregulated PTEN levels. Abstract: NPs showed enhanced cytotoxicity against MDA-MB-231 and A549 cells. Abstract: Targeted combination therapy has shown promise to achieve maximum therapeutic efficacy by overcoming drug resistance. MicroRNA-21 (miR-21) is frequently overexpressed in various cancer types including breast and non-small cell lung cancer and its functions can be inhibited by miR inhibitor (miR-21i). A combination of miR-21i and a chemo drug, doxorubicin (Dox), can provide synergistic effects. Here, we developed a calcium phosphate (CaP)-coated nanoparticle (NP) formulation to co-deliver miR-21i along with Dox. This NP design can be used to deliver the two agents with different physiochemical properties. The NP formulation was optimized for particle size, polydispersity, Dox loading, and miR-21i loading. The NP formulation was confirmed to downregulate miR-21 levels and upregulate tumor suppressor gene levels. The cytotoxic efficacy of the combined miR-21i and Dox-containing NPs was found to be higher than that of Dox. Therefore, the CaP-coated hybrid lipid-polymeric NPs hold potential for the delivery of miR-21i and Dox. Keywords: Polymeric nanoparticles Calcium phosphate microRNA-21 inhibitor Doxorubicin Co-delivery Combination therapy”

mPEG-PLGA from PolySciTech used in development of microfluidic nanoparticles for delivery of peptides

Friday, September 24, 2021, 4:10 PM ET

Peptides represents an important and useful class of drugs which are limited due to their rapid breakdown in the blood stream. Recently researchers from The University of Queensland, National Center for Nanoscience and Technology, and Southern University of Science and Technology (China), mPEG-PLGA (Cat# AK026) from PolySciTech (www.polyscitech.com) was used for peptide delivery. This research holds promise to improve the longevity of peptide drugs thus extending their usefulness. Read More: Han, Felicity Y., Weizhi Xu, Vinod Kumar, Cedric S. Cui, Xaria Li, Xingyu Jiang, Trent M. Woodruff, Andrew K. Whittaker, and Maree T. Smith. "Optimisation of a Microfluidic Method for the Delivery of a Small Peptide." Pharmaceutics 13, no. 9 (2021): 1505. https://www.mdpi.com/1276894

“Abstract: Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases. Keywords: drug delivery system; nanoparticles; poly (lactic-co-glycolic acid) (PLGA); microfluidic; pharmacokinetics (PK) and biodistribution”

PLGA from PolySciTech Used in development of intracellular delivery systems.

Friday, September 24, 2021, 4:09 PM ET

The ability to deliver medicines and genetic materials into a cell can be a powerful tool to treat disease. Recently, researchers at University of Connecticut and University of Iowa purchased PLGA from PolySciTech (www.polyscitech.com) to create poly(histidine)-PLGA mixed nanoparticles. They researched the use of this as a way to deliver nanoparticles into cells. This research holds promise to improve intracellular delivery. Read more: Wahane, Aniket, Shipra Malik, Kuo-Chih Shih, Ravinder Reddy Gaddam, Chaohao Chen, Yun Liu, Mu-Ping Nieh, Ajit Vikram, and Raman Bahal. "Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy." ACS Applied Materials & Interfaces (2021). https://pubs.acs.org/doi/abs/10.1021/acsami.1c11981

“Abstract: Cationic polymeric nanoformulations have been explored to increase the transfection efficiency of small molecules and nucleic acid-based drugs. However, an excessive positive charge density often leads to severe cell and tissue-based toxicity that restricts the clinical translation of cationic polymeric nanoformulations. Herein, we investigate a series of cationic poly(lactic-co-glycolic acid) (PLGA)-histidine-based nanoformulations for enhanced cytoplasmic delivery with minimal toxicity. PLGA/poly-l-histidine nanoparticles show promising physico-biochemical features and transfection efficiency in a series of in vitro and cell culture-based studies. Further, the use of acetone/dichloromethane as a solvent mixture during the formulation process significantly improves the morphology and size distribution of PLGA/poly-l-histidine nanoparticles. PLGA/poly-l-histidine nanoformulations undergo clathrin-mediated endocytosis. A contrast-matched small-angle neutron scattering experiment confirmed poly-l-histidine’s distribution on the PLGA nanoformulations. PLGA/poly-l-histidine formulations containing paclitaxel as a small molecule-based drug and peptide nucleic acids targeting microRNA-155 as nucleic acid analog are efficacious in in vitro and in vivo studies. PLGA/poly-l-histidine NPs significantly decrease tumor growth in PNA-155 (∼6 fold) and paclitaxel (∼6.5 fold) treatment groups in a lymphoma cell line derived xenograft mice model without inducing any toxicity. Hence, PLGA/poly-l-histidine nanoformulations exhibit substantial transfection efficiency and are safe to deliver reagents ranging from small molecules to synthetic nucleic acid analogs and can serve as a novel platform for drug delivery. KEYWORDS: poly-l-histidine PLGA nanoparticles proton-sponge effect microRNAs”

PLGA from PolySciTech used in development of Long-Acting implant for vaccination against Covid-19 variants

Thursday, September 16, 2021, 2:32 PM ET

The way in which an antigen or other structure is presented to the immune system has an effect on how strong the immune system develops a response against that particular antigen. Notably, for vaccination, it is optimal to provide an antigen to the immune system over an extended time to maximize vaccine efficacy. Recently, researchers at University of California, San Diego loaded antigens that are conserved between variants of concern (i.e. similar antigen structures that show up in multiple viral variants despite their other differences) into a PLGA/PEG rod extrusion mix comprised of PLGA (cat# AP041) from PolySciTech (www.polyscitech.com) to create a slow-release antigen rod which was both stable at room temperature and eliminated the need for follow-up innoculations. This research holds promise for improving protections against both the current pandemic as well as future pandemic’s yet to come. Read more: Ortega-Rivera, Oscar A., Matthew D. Shin, Angela Chen, Veronique Beiss, Miguel A. Moreno-Gonzalez, Miguel A. Lopez-Ramirez, Maria Reynoso et al. "Trivalent Subunit Vaccine Candidates for COVID-19 and Their Delivery Devices." Journal of the American Chemical Society (2021). https://pubs.acs.org/doi/abs/10.1021/jacs.1c06600

“The COVID-19 pandemic highlights the need for platform technologies enabling rapid development of vaccines for emerging viral diseases. The current vaccines target the SARS-CoV-2 spike (S) protein and thus far have shown tremendous efficacy. However, the need for cold-chain distribution, a prime-boost administration schedule, and the emergence of variants of concern (VOCs) call for diligence in novel SARS-CoV-2 vaccine approaches. We studied 13 peptide epitopes from SARS-CoV-2 and identified three neutralizing epitopes that are highly conserved among the VOCs. Monovalent and trivalent COVID-19 vaccine candidates were formulated by chemical conjugation of the peptide epitopes to cowpea mosaic virus (CPMV) nanoparticles and virus-like particles (VLPs) derived from bacteriophage Qβ. Efficacy of this approach was validated first using soluble vaccine candidates as solo or trivalent mixtures and subcutaneous prime-boost injection. The high thermal stability of our vaccine candidates allowed for formulation into single-dose injectable slow-release polymer implants, manufactured by melt extrusion, as well as microneedle (MN) patches, obtained through casting into micromolds, for prime-boost self-administration. Immunization of mice yielded high titers of antibodies against the target epitope and S protein, and data confirms that antibodies block receptor binding and neutralize SARS-CoV and SARS-CoV-2 against infection of human cells. We present a nanotechnology vaccine platform that is stable outside the cold-chain and can be formulated into delivery devices enabling single administration or self-administration. CPMV or Qβ VLPs could be stockpiled, and epitopes exchanged to target new mutants or emergent diseases as the need arises.”

PLGA from PolySciTech used in bacteria-mediated drug-delivery system development

Wednesday, September 15, 2021, 2:52 PM ET

There are many ways to make drug-delivery systems and for operating at such small-scale often it is advantageous to employ microorganisms to help with this. Recently, researchers at Virginia Tech used PLGA (Cat# AP082) from PolySciTech (www.polyscitech.com) to create bacteria-attaching nanobeads for using the bacteria to help deliver drug molecules. This research represents a novel paradigm in drug-delivery technologies. Read more: Zhan, Ying, Austin Fergusson, Lacey R. McNally, Richey M. Davis, and Bahareh Behkam. "Robust and Repeatable Biofabrication of Bacteria-Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size." Authorea Preprints (2021). https://www.authorea.com/doi/full/10.22541/au.163100509.93917936

“Abstract: Bacteria-mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics' bioavailability and reduce systemic toxicity, while bacteria selectively colonize the cancerous tissue, impart intrinsic and immune-mediated antitumor effects, and propel nanotherapeutics interstitially. The optimal bacteria-nanoparticle (NP) conjugates would carry the maximal NP load with minimal motility speed hindrance for effective interstitial distribution. Furthermore, a well-defined and repeatable NP attachment density distribution is crucial to determining these biohybrid systems' efficacious dosage and robust performance. Herein, we utilized our Nanoscale Bacteria-Enabled Autonomous Delivery System (NanoBEADS) platform to investigate the effects of assembly process parameters of mixing method, volume, and duration on NP attachment density and repeatability. We also evaluated the effect of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS. We show that the linkage chemistry impacts NP attachment density while the self-assembly process parameters affect the repeatability and, to a lesser extent, attachment density. Lastly, the attachment density affects NanoBEADS' growth rate and motility in an NP size-dependent manner. These findings will contribute to the development of scalable and repeatable bacteria-nanoparticle biohybrids for applications in drug delivery and beyond.”

PEG-PLGA from PolySciTech used in development of Boron Neutron capture therapy to treat prostate cancer

Wednesday, September 15, 2021, 2:51 PM ET

One therapy for cancer is to apply targeted radiation treatment to remove the tumor that route. To do this a sensitizer or comparable compound is loaded into a targeted system designed to specifically accumulate in the tumor site. Then the area is affected by a relatively inert force (such as low-energy neutrons) to induce a radioactive response. Recently, researchers at UCSF purchased PEG-PLGA (cat# AK037) and PLGA-PEG-COOH (cat# AI078) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with boron for delivery to prostate cancers. This enables treatment of the cancer by exposing the area to neutrons which then cause the boron to emit alpha radiation in a localized manner. This research holds promise to improve therapeutic options against difficult cancers in the future. Read more: Dhrona, Suchi. "Development of PSMA Targeted Polymer Nanoparticles to Treat Prostate Cancer By Boron Neutron Capture Therapy Directed Against PSMA." PhD diss., UCSF, 2021. https://escholarship.org/content/qt6c6292zv/qt6c6292zv.pdf

“Prostate-specific membrane antigen (PSMA) is a cell surface enzyme highly over expressed in prostate cancer cells that can be employed as a target for prostate cancer imaging and drug delivery. Boron Neutron Capture Therapy (BNCT) is an emerging noninvasive therapeutic modality for treating locally invasive malignant tumors by selective delivery of high boron content to the tumour and then subjecting the tumour to epithermal neutron beam radiation. In this study, we develop carborane encapsulated amphiphilic polymer nanoparticles by conjugating urea based PSMA inhibitors (ACUPA) and 89Zr chelating deferoxamine B (DFB) ligand and have investigated their efficacy to deliver enhanced boron payload to PSMA positive prostate cancer cells with simultaneous positron emission tomography (PET) imaging . Three different carborane encapsulated PLGA-b-PEG nanoparticles (NPs) were formulated with and without the PSMA targeting ligand, out of which two selected formulations; DFB(25)ACUPA(75) NPs and DFB(25) NPs radiolabelled with 89Zr were administered to mice bearing dual PSMA(+) PC3-Pip and PSMA(-) PC3-Flu xenografts. PET imaging and biodistribution studies were performed to demonstrate the in vivo uptake in mice. The NPs showed 2-fold higher uptake in PSMA(+) PC3-Pip tumors to that of PSMA(-) PC3-Flu tumors with a very high tumor/blood ratio of 20. However, no significant influence of the ACUPA ligands were observed. Additionally, the NPs demonstrated fast release of carborane with low delivery of boron to tumors in vivo. Although the in vivo afficacy of those NPs remain limited, a significant progress towards the synthesis, characterization and initial biological evaluation of the polymer nanoparticles is proposed in this report and the results presented could guide the future design of amphiphilic polymer NPs for theranostic applications.”

PEG-PLGA from PolySciTech used in development of curcumin-based therapy for ocular cancer treatment

Thursday, September 2, 2021, 9:04 AM ET

Curcumin is a powerful anti-oxidant compound which has properties that prevent tumor metastasis and motion. Although it is present in turmeric, simply eating turmeric (or turmeric powder/prepared foods) will not provide patients with any therapeutically meaningful quantity of curcumin as this compound has very bad water solubility and does not cross over the intestinal tract well. That being said, curcumin provided in a carrier formulation as an injectable or otherwise deliverable compound can aid in cancer treatment. Recently, researchers at University of Rhode Island used PEG-PLGA (AK026) from PolySciTech (www.polyscitech.com) to produce curcumin-loaded nanoparticles. They embedded these in a thermosensitive gel and tested the system for use against uveal melanoma. This treatment holds promise to improve therapies against cancer. Read more: Xie, Lingxiao, Weizhou Yue, Khaled Ibrahim, and Jie Shen. "A Long-Acting Curcumin Nanoparticle/In Situ Hydrogel Composite for the Treatment of Uveal Melanoma." Pharmaceutics 13, no. 9 (2021): 1335. https://www.mdpi.com/1243808

“Uveal melanoma (UM) is the most common primary intraocular tumor in adults with high mortality. In order to improve prognosis and survival of UM patients, it is critical to inhibit tumor progression and metastasis as early as possible after the initial presentation/diagnosis of the disease. Sustained local delivery of antitumor therapeutics in the posterior region can potentially achieve long-term UM inhibition, improve target therapeutic delivery to the posterior segments, as well as reduce injection frequency and hence improved patient compliance. To address the highly unmet medical need in UM therapy, a bioinspired in situ gelling hydrogel system composed of naturally occurring biopolymers collagen and hyaluronic acid was developed in the present research. Curcumin with anti-cancer progression, anti-metastasis effects, and good ocular safety was chosen as the model therapeutic. The developed in situ gelling delivery system gelled at 37 °C within two minutes and demonstrated excellent biocompatibility and slow degradation. The curcumin-loaded nanoparticle/hydrogel composite was able to sustain release payload for up to four weeks. The optimized nanoparticle/hydrogel composite showed effective inhibition of human UM cell proliferation. This novel nanoparticle/in situ hydrogel composite demonstrated a great potential for the treatment of the rare and devastating intraocular cancer. Keywords: in situ hydrogel; nanoparticle/hydrogel composite; sustained delivery; curcumin; uveal melanoma”

PEG-PLGA and PLGA from PolySciTech used in research on nanoparticle fate within the brain

Tuesday, August 31, 2021, 10:13 AM ET

Nanoparticle motion within the brain is a complicated process which is driven by the various chemical factors involved with cellular recognition and disposition towards the particles as well as the particle tendency to aggregate or ability to cross membranes. Recently, researchers from University of Washington used PEG-PLGA (AK106) and PLGA (AP059) to create a series of nanoparticles with varying surfactant-related exteriors. They then fluorescently stained these polymers and carefully tracked their motion through brain tissue to determine their motility and fate. This research holds promise to improve future nanoparticle derived therapies against brain diseases. Read more: Joseph, Andrea, Georges Motchoffo Simo, Torahito Gao, Norah Alhindi, Nuo Xu, Daniel J. Graham, Lara J. Gamble, and Elizabeth Nance. "Surfactants influence polymer nanoparticle fate within the brain." Biomaterials (2021): 121086. https://www.sciencedirect.com/science/article/pii/S0142961221004427

“Abstract: Drug delivery to the brain is limited by poor penetration of pharmaceutical agents across the blood-brain barrier (BBB), within the brain parenchyma, and into specific cells of interest. Nanotechnology can overcome these barriers, but its ability to do so is dependent on nanoparticle physicochemical properties including surface chemistry. Surface chemistry can be determined by a number of factors, including by the presence of stabilizing surfactant molecules introduced during the formulation process. Nanoparticles coated with poloxamer 188 (F68), poloxamer 407 (F127), and polysorbate 80 (P80) have demonstrated uptake in BBB endothelial cells and enhanced accumulation within the brain. However, the impact of surfactants on nanoparticle fate, and specifically on brain extracellular diffusion or intracellular targeting, must be better understood to design nanotherapeutics to efficiently overcome drug delivery barriers in the brain. Here, we evaluated the effect of the biocompatible and commonly used surfactants cholic acid (CHA), F68, F127, P80, and poly(vinyl alcohol) (PVA) on poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticle transport to and within the brain. The inclusion of these surfactant molecules decreases diffusive ability through brain tissue, reflecting the surfactant's role in encouraging cellular interaction at short length and time scales. After in vivo administration, PLGA-PEG/P80 nanoparticles demonstrated enhanced penetration across the BBB and subsequent internalization within neurons and microglia. Surfactants incorporated into the formulation of PLGA-PEG nanoparticles therefore represent an important design parameter for controlling nanoparticle fate within the brain.”

PLGA-PEG-Mal from PolySciTech used in research on antibody-targeting of nanoparticles

Monday, August 23, 2021, 10:55 AM ET

Use of antibodies for generation of targeted nanoparticles is a popular mechanism used within drug-delivery systems to provide for localization of drug molecules. However, since anitbodies have specific 3-dimensional shapes as a result of the various parameters including folding and orientation of the molecule, the manner in which they are attached plays a role in their performance. Recently, researchers at Sungkyunkwan University and Chung-Ang University (Korea) used PLGA-PEG-Mal (AI053) and PLGA (AP041) from PolySciTech to generate reactive nanoparticles for antibody adhesion testing. This research holds promise to improve development of targeted nanoparticles in the future. Lee, Na Kyeong, Chi-Pin James Wang, Jaesung Lim, Wooram Park, Ho-Keun Kwon, Se-Na Kim, Tae-Hyung Kim, and Chun Gwon Park. "Impact of the conjugation of antibodies to the surfaces of polymer nanoparticles on the immune cell targeting abilities." Nano Convergence 8, no. 1 (2021): 1-11. https://nanoconvergencejournal.springeropen.com/articles/10.1186/s40580-021-00274-7

“Abstract: Antibodies have been widely used to provide targeting ability and to enhance bioactivity owing to their high specificity, availability, and diversity. Recent advances in biotechnology and nanotechnology permit site-specific engineering of antibodies and their conjugation to the surfaces of nanoparticles (NPs) in various orientations through chemical conjugations and physical adhesions. This study proposes the conjugation of poly(lactic-co-glycolic acid) (PLGA) NPs with antibodies by using two distinct methods, followed by a comparison between the cell-targeting efficiencies of both techniques. Full-length antibodies were conjugated to the PLGA-poly(ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) NPs through the conventional carbodiimide coupling reaction, and f(ab′)2 antibody fragments were conjugated to the PLGA-poly(ethylene glycol)-maleimide(PLGA-PEG-Mal) NPs through interactions between the f(ab′)2 fragment thiol groups and the maleimide located on the nanoparticle surface. The results demonstrate that the PLGA nanoparticles conjugated with the f(ab′)2 antibody fragments had a higher targeting efficiency in vitro and in vivo than that of the PLGA nanoparticles conjugated with the full-length antibodies. The results of this study can be built upon to design a delivery technique for drugs through biocompatible nanoparticles.”

Chitosan-fluorescein from PolySciTech used in development of bioadhesive glue for surgical repair

Monday, August 23, 2021, 10:54 AM ET

A valuable tool for use in either surgery or treatment of traumatic injuries is an adhesive which can stick to human tissues and bind them together for a period of time before biodegrading away. Recently, researchers at Massachusetts Institute of Technology used Chitosan-Fluorescein (Kito-8) from PolySciTech (www.polyscitech.com) as part of their development of a glue system for surgical repair applications. This research holds promise to improve wound treatment and tissue repair. Read more: Yuk, Hyunwoo, Jingjing Wu, Tiffany L. Sarrafian, Xinyu Mao, Claudia E. Varela, Ellen T. Roche, Leigh G. Griffiths, Christoph S. Nabzdyk, and Xuanhe Zhao. "Rapid and coagulation-independent haemostatic sealing by a paste inspired by barnacle glue." Nature Biomedical Engineering (2021). https://www.nature.com/articles/s41551-021-00769-y.pdf?origin=ppub

“Abstract: Tissue adhesives do not normally perform well on tissues that are covered with blood or other bodily fluids. Here we report the design, adhesion mechanism and performance of a paste that haemostatically seals tissues in less than 15 s, independently of the blood-coagulation rate. With a design inspired by barnacle glue (which strongly adheres to wet and contaminated surfaces owing to adhesive proteins embedded in a lipid-rich matrix), the paste consists of a blood-repelling hydrophobic oil matrix containing embedded microparticles that covalently crosslink with tissue surfaces on the application of gentle pressure. It slowly resorbs over weeks, sustains large pressures (approximately 350 mm Hg of burst pressure in a sealed porcine aorta), makes tough (interfacial toughness of 150–300 J m−2) and strong (shear and tensile strengths of, respectively, 40–70 kPa and 30–50 kPa) interfaces with blood-covered tissues, and outperforms commercial haemostatic agents in the sealing of bleeding porcine aortas ex vivo and of bleeding heart and liver tissues in live rats and pigs. The paste may aid the treatment of severe bleeding, even in individuals with coagulopathies.”

PEG-PLGA from PolySciTech used in development of macitentan particles to prime tumors for immunotherapy

Tuesday, August 17, 2021, 10:12 AM ET

Immunotherapy holds great promise to provide for treatments against cancers by relying on the human immune system to target and destroy the cancer cells. Unfortunately, tumors have a wide array of protecting themselves from immune system which must be overcome in order for immunotherapy to be effective. Recently, researchers at Sungkyunkwan University, National Marine Biodiversity Institute of Korea, and Korea Research Institute of Bioscience & Biotechnology used mPEG-PLGA (AK037) from PolySciTech (www.polyscitech.com) to create polymeric micelle nanoparticles containing macitentan which reduces the ability for the tumor to suppress immune response. This research holds promise to improve the application of immunotherapy. Read more: Son, Soyoung, Jung Min Shin, Sol Shin, Chan Ho Kim, Jae Ah Lee, Hyewon Ko, Eun Sook Lee, Jae Min Jung, Jeongyun Kim, and Jae Hyung Park. "Repurposing macitentan with nanoparticle modulates tumor microenvironment to potentiate immune checkpoint blockade." Biomaterials (2021): 121058. https://www.sciencedirect.com/science/article/pii/S0142961221004142

“Abstract: Immune checkpoint therapy (ICT), which reinvigorates cytotoxic T cells, provides clinical benefits as an alternative to conventional cancer therapies. However, its clinical response rate is too low to treat an immune-excluded tumor, owing to the presence of abundant stromal elements impeding the penetration of immune cells. Here, we report that macitentan, a dual endothelin receptor antagonist approved by the FDA to treat pulmonary arterial hypertension, can be repositioned to modulate the desmoplastic tumor microenvironment (TME). In the 4T1 orthotopic tumor model, the polymeric nanoparticles bearing macitentan (M-NPs) prevent fibrotic progression by regulating the function of cancer-associated fibroblasts, attenuate the biogenesis of cancer cell-derived exosomes, and modulate the T cell subsets and distribution in TME. These results demonstrate that the M-NPs effectively reorganize the immunosuppressive TME by targeting the endothelin-1 axis and consequently exhibit synergistic antitumor effects in combination with ICT.”

mPEG-PLA and PLA from PolySciTech used in development of novel block copolymers for nanoparticle formulations

Tuesday, August 10, 2021, 11:50 AM ET

In most situations PEGylated particles provide for highly-safe mechanisms to improve flow and residence time of particles in the human body. In specific instances, however, certain people will develop an immune reaction to PEG itself which limits the usefulness of these particles. Recently, researchers at Universita degli Studi di Salerno (University of Salerno, Fiscaiano, Italy) used PLA (AP005, AP079) and mPEG-PLA (AK009) from PolySciTech (www.polyscitech.com) to create nanoparticles with PEGylated exteriors as well as particles with a nove inulin coating. This research indicates that inulin can be used as an alternative to PEG for use in people who have experienced allergic reactions to PEG. Read more: Sardo, Carla, Teresa Mencherini, Carmela Tommasino, Tiziana Esposito, Paola Russo, Pasquale Del Gaudio, and Rita Patrizia Aquino. "Inulin-g-poly-D, L-lactide, a Sustainable Amphiphilic Copolymer for Nano-Therapeutics." (2021). https://www.researchsquare.com/article/rs-703619/latest.pdf

“Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy whilst maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, although in many cases is a winning choice to ensure a long circulation and colloidal stability, in other cases cause, after the first administration, the development in patients of PEG directed immunoglobulins. The phenomenon, called ABC effect, has been studied and correlated with clinical failure because of the premature removal from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility and its GRAS status, the natural polysaccharide Inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-gpoly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physic-chemical point of view (solubility, 1D and 2D NMR, FT-IR, UV-Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well known and well characterized PEGylated counterpart, polyethylene glycol-g-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues. Keywords: Inulin, PLA, PEG alternative, nanoparticles, doxorubicin”

PLCL Morphological Form based on LA:CL ratio

Monday, August 9, 2021, 10:19 AM ET

Poly(lactide-co-caprolactone) has a varying degree to glass and melt transitions depending on the LA:CL ratio. In general, the closer the LA:CL ratio is to either end (primarily LA or primarily CL) then crystallinity is enabled for chain-to-chain attraction. When the LA:CL is close to 50:50 mix between the two components then the product has a very low glass transition and melt point with little chain-to-chain interaction. Additionally, the use of more crystalline L-enantiomer lactide improves mechanical durability as well. The morphology (at room temperature) of several of Akina's Products demonstrates this:

Morphology at room temperature (RT):

AP151: PLCL LA:CL 70:30 acid endcap (Mn 75,000-85,000 Da) DL-enantiomer
--> pale straw-colored translucent polymer. Rubbery texture at RT.

AP260: PLLCL LA:CL 90:10 acid endcap (Mn 100,000-200,000 Da) (L-enantiomer)
--> opaque, fluffy, white at RT. Feels dry to the touch.

AP263: PLCL LA:CL 80:20 acid endcap (Mn 75,000-85,000 Da) DL-enantiomer
--> translucent white at room temp. Rubbery texture.

Akina Scientific Posters from 2021 Controlled Release Society now available in full-content pdf

Thursday, August 5, 2021, 10:18 AM ET

As part of work with the Food and Drug Administration (FDA), Akina, Inc. has performed many experiments relating to development work in characterization methods for poly(lactide-co-glycolide) (PLGA). At the 2021 Controlled Release Society annual meeting scientific posters were presented relating to these experiments and their results. Akina, Inc. provides contracted analysis and research for outside customers through the Akinalytics (http://www.akinalytics.com/) department. You can see these and other publications from Akina, Inc. at our listing here (http://polyscitech.com/currentResearch/publications.php)

J. Garner, J. Hadar, S. Skidmore, F. Jessmon, H. Park, K. Park, Y. K. Jhon, B. Qin, Y. Wang. “Scanning Analysis of Semi-Solvent Impact (SASSI) assays of naltrexone microparticles manufactured using different solvents” Scientific Poster presented at 2021 annual meeting of Controlled Release Society

J. Garner, J. Hadar, S. Skidmore, F. Jessmon, H. Park, K. Park, Y. K. Jhon, B. Qin, Y. Wang. “Effect of Solvent Isomeric Structures on the Dissolution of PLGAs with Different Lactide:Glycolide (L:G) Ratios” Scientific Poster presented at 2021 annual meeting of Controlled Release Society

J. Garner, J. Hadar, S. Skidmore, F. Jessmon, H. Park, K. Park, Y. K. Jhon, B. Qin, Y. Wang. “Effect of Solvent Isomeric Structures on the Dissolution of PLGAs with Different Lactide:Glycolide (L:G) Ratios” Scientific Poster presented at 2021 annual meeting of Controlled Release Society

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.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.28357100486755 seconds)


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