Technical Blog
John GarnerJohn Garner, General Manager

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


Select a topic to hide all other entries.
The most recent item is at the top.

PEG-PLGA from PolySciTech used in development of nanoparticles with fluorescent bar-coding for in-vitro assay applications

Thursday, May 25, 2023, 3:06 PM ET

Many biological assays rely on the interactions of various compounds with either surfaces or particles. Due to their small size and high number tracking of individual particles is not a trivial task or feasible means to interpret in-vitro or diagnostic data. However, the addition of fluorescent coding and advanced software processing may enable use of particle behavior as part of testing kits/assays. Researchers at Eindhoven University of Technology used PEG-PLGA (cat# AK102) and PLGA (cat# AP082) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create traceable nanoparticles and tested these for use in a variety of assay kits. This research holds promise to improve both learning of biochemical interactions and diagnostic applications in the future. Read more: Ortiz-Perez, Ana, Cristina Izquierdo-Lozano, Rens Meijers, Francesca Grisoni, and Lorenzo Albertazzi. "Identification of fluorescently-barcoded nanoparticles using machine learning." Nanoscale Advances 5, no. 8 (2023): 2307-2317. https://pubs.rsc.org/en/content/articlehtml/2023/na/d2na00648k

“Barcoding of nano- and micro-particles allows distinguishing multiple targets at the same time within a complex mixture and is emerging as a powerful tool to increase the throughput of many assays. Fluorescent barcoding is one of the most used strategies, where microparticles are labeled with dyes and classified based on fluorescence color, intensity, or other features. Microparticles are ideal targets due to their relative ease of detection, manufacturing, and higher homogeneity. Barcoding is considerably more challenging in the case of nanoparticles (NPs), where their small size results in a lower signal and greater heterogeneity. This is a significant limitation since many bioassays require the use of nano-sized carriers. In this study, we introduce a machine-learning-assisted workflow to write, read, and classify barcoded PLGA–PEG NPs at a single-particle level. This procedure is based on the encapsulation of fluorescent markers without modifying their physicochemical properties (writing), the optimization of their confocal imaging (reading), and the implementation of a machine learning-based barcode reader (classification). We found nanoparticle heterogeneity as one of the main factors that challenges barcode separation, and that information extracted from the dyes' nanoscale confinement effects (such as Förster Resonance Energy Transfer, FRET) can aid barcode identification. Moreover, we provide a guide to reaching the optimal trade-off between the number of simultaneous barcodes and classification accuracy supporting the use of this workflow for a variety of bioassays.”

Video: https://youtu.be/e3NeqhsQ4cY

Bulk, empty bottles and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

PLGA from PolySciTech used in development of treatment for inflammatory brain condition

Thursday, May 25, 2023, 3:06 PM ET

Many different conditions can lead to inflammation within the delicate brain tissue of a patient. One means of reducing damage to the brain caused by a variety of disease or trauma states is to limit the inflammatory response. Researchers at University of Kentucky used PLGA (cat# AP081) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create conjugated nanoparticles to target microglia. This research holds promise to improve therapy against inflammatory brain conditions. Read more: Kalashnikova, Irina, Heather Cambell, Daniel Kolpek, and Jonghyuck Park. "Optimization and characterization of miRNA-129-5p-encapsulated poly (lactic-co-glycolic acid) nanoparticle to reprogram activated microglia." Nanoscale Advances (2023). https://pubs.rsc.org/en/content/articlehtml/2023/na/d3na00149k

“Abstract: Microglia have become a therapeutic target of many inflammation-mediated diseases in the central nervous system (CNS). Recently, microRNA (miRNA) has been proposed as an important regulator of immune responses. Specifically, miRNA-129-5p has been shown to play critical roles in the regulation of microglia activation. We have demonstrated that biodegradable poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modulated innate immune cells and limited neuroinflammation after injury to the CNS. In this study, we optimized and characterized PLGA-based NPs for miRNA-129-5p delivery to utilize their synergistic immunomodulatory features for activated microglia modulation. A series of nanoformulations employing multiple excipients including epigallocatechin gallate (EGCG), spermidine (Sp), or polyethyleneimine (PEI) for miRNA-129-5p complexation and miRNA-129-5p conjugation to PLGA (PLGA-miR) were utilized. We characterized a total of six nanoformulations through physicochemical, biochemical, and molecular biological methods. In addition, we investigated the immunomodulatory effects of multiple nanoformulations. The data indicated that the immunomodulatory effects of nanoformulation, PLGA-miR with the excipient Sp (PLGA-miR+Sp) and PEI (PLGA-miR+PEI) were significant compared to other nanoformulations including naked PLGA-based NP. These nanoformulations promoted a sustained release of miRNA-129-5p and polarization of activated microglia into a more pro-regenerative phenotype. Moreover, they enhanced the expression of multiple regeneration-associated factors, while alleviating the expression of pro-inflammatory factors. Collectively, the proposed nanoformulations in this study highlight the promising therapeutic tools for synergistic immunomodulatory effects between PLGA-based NPs and miRNA-129-5p to modulate activated microglia which will have numerous applications for inflammation-derived diseases.”

Video: https://youtu.be/MB9Q8Fn9nbA

Bulk, empty bottles and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

Website Temporary Outages

Monday, May 22, 2023, 2:32 PM ET

Date - 5/22/2023:

Due to routine maintenance, portions of akinainc.com (PolySciTech and Akinalytics) website will experience temporary outages and problems. Thank you for your patience as we work to resolve this issue.

PLGA-PEG-NHS from PolySciTech used in development of novel targeted nanoparticle therapy

Thursday, May 11, 2023, 4:35 PM ET

Nanoparticles can be used to provide for improved blood circulation and drug targeting to specific locations within the body. There are many different designs for creating targeted nanoparticles for treating different diseases. Researchers at Queen's University Belfast, University of Aberdeen, and Elasmogen Ltd. used PLGA-PEG-NHS (AI064) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescent nanoparticles with vinyl sulfone functionality. This research holds promise to provide for improved drug delivery methodologies. Read more: Leach, Adam, Marie Finnegan, Mariana Stefani Machado, Laura Ferguson, John Steven, Peter Smyth, Andrew Porter, Caroline Barelle, Efrosyni Themistou, and Christopher J. Scott. "Functionalization of polymeric nanoparticles with targeting VNAR ligands using vinyl sulfone conjugation." Journal of Materials Chemistry B (2023). https://pubs.rsc.org/en/content/articlehtml/2023/tb/d2tb01985j

“Abstract: Actively targeted drug loaded nanoparticles represent an exciting new form of therapeutics for cancer and other diseases. These formulations are complex and in order to realize their ultimate potential, optimization of their preparation is required. In this current study, we have examined the conjugation of a model targeting ligand, conjugated in a site-specific manner using a vinyl sulfone coupling approach. A disulfide-functionalized poly(L-lactide)-b-poly(oligo(ethylene glycol) methacrylate)-stat-(bis(2-methacryloyl)oxyethyl disulfide) (PLA-b-P(OEGMA-stat-DSDMA)) diblock copolymer was synthesized by simultaneous ring opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. Subsequently, the disulfide bonds of the polymer were reduced to thiols and divinyl sulfone was attached to the polymer using thiol–ene chemistry to produce the vinyl sulfone (VS)-functionalized PLA-b-P(OEGMA-stat-VSTEMA) amphiphilic block copolymer. Single emulsion – solvent evaporation was employed using a blend of this polymer with poly(D,L-lactide-co-glycolide) (PLGA) to produce VS-functionalized polymeric nanoparticles. The ability of these novel nanoparticles to attach ligands was then exemplified using a single domain variable new antigen receptor (VNAR) with a free carboxyl terminal cysteine residue. The resulting VNAR-functionalized nanoparticles were found to maintain specific affinity to their cognate antigen (DLL4) for at least 72 h at 4 °C. The simplicity of the degradable amphiphilic block copolymer synthesis and the efficiency of VNAR conjugation to the VS-functionalized nanoparticles show the potential of this platform for therapeutic development.”

Video: https://youtu.be/0nO2MGNR0tA

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

PLA-cyanine 5 from PolySciTech used in development of nanoparticles for research on circulation and transport

Wednesday, May 10, 2023, 4:03 PM ET

Nanoparticles can be utilized to improve drug delivery to living systems. However, a great deal still remains to be learned about their transportation through the body. Researchers at Yale University and Inha University (Korea) used PLA-CY5 (AV032) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescent nanoparticle to track their transport through living systems. This research holds promise to improve nanoparticle delivery systems. Read more: Grundler, Julian, Kwangsoo Shin, Hee-Won Suh, Chang-Hee Whang, and W. Mark Saltzman. "Prolonged Circulation and Enhanced Tumor Uptake of PEGylated Nanoparticles by Manipulation of Nanoscale Surface Topography." (2023). https://chemrxiv.org/engage/chemrxiv/article-details/64504e5f80f4b75b53745c09

“Improving the performance of nanocarriers remains a major challenge in the clinical translation of nanomedicine. Efforts to optimize nanoparticle formulations typically rely on tuning the surface density and thickness of stealthy polymer coatings such as poly(ethylene glycol) (PEG). Here, we show that modulating the surface topography of PEGylated nanoparticles using bottlebrush block copolymer (BBCP) significantly enhances circulation and tumor accumulation providing an alternative strategy to improve nanoparticle coatings. Specifically, nanoparticles with rough surface topography achieve high tumor cell uptake in vivo due to superior tumor extravasation and distribution compared to conventional smooth-surfaced nanoparticles. Furthermore, surface topography profoundly impacts the interaction with serum proteins resulting in the adsorption of fundamentally different proteins onto the surface of rough-surfaced nanoparticles formed from BBCPs. We envision that controlling the nanoparticle surface topography of PEGylated nanoparticles will enable the design of improved nanocarriers in various biomedical applications.”

Video: https://youtu.be/_5rnkwCLLgg

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles from pandemic-era hand-sanitizer manufacturing and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

PEG-PCL block copolymers from PolySciTech used in development of treatment of ovarian cancer

Wednesday, May 10, 2023, 4:02 PM ET

Ovarian cancer is a common and fatal disease. A woman's lifetime risk of developing ovarian cancer is 1 in 78. A woman's lifetime risk of dying from invasive ovarian cancer is 1 in 108. Researchers at Sungkyunkwan University School of Medicine and Chungbuk National University utilized mPEG-PCL (Cat# AK073) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create micelles loaded with fenbendazole and rapamycin for treatment of ovarian cancer. This research holds promise to improve therapy against this deadly disease. Read more: Shin, Yu Been, Ju-Yeon Choi, Dae Hwan Shin, and Jeong-Won Lee. "Anticancer Evaluation of Methoxy Poly (Ethylene Glycol)-b-Poly (Caprolactone) Polymeric Micelles Encapsulating Fenbendazole and Rapamycin in Ovarian Cancer." International Journal of Nanomedicine (2023): 2209-2223. https://www.tandfonline.com/doi/abs/10.2147/IJN.S394712

“Abstract: We aimed to inhibit ovarian cancer (OC) development by interfering with microtubule polymerization and inhibiting mTOR signaling. To achieve this, previously developed micelles containing fenbendazole and rapamycin were applied. Herein, we prepared micelles for drug delivery using fenbendazole and rapamycin at a 1:2 molar ratio and methoxy poly(ethylene glycol)-b-poly(caprolactone)(mPEG-b-PCL) via freeze-drying. We revealed their long-term storage capacity of up to 120 days. Furthermore, a cytotoxicity test was performed on the OC cell line HeyA8, and an orthotopic model was established for evaluating in vivo antitumor efficacy. Fenbendazole/rapamycin-loaded mPEG-b-PCL micelle (M-FR) had an average particle size of 37.2 ± 1.10 nm, a zeta potential of −0.07 ± 0.09 mV, and a polydispersity index of 0.20 ± 0.02. Additionally, the average encapsulation efficiency of fenbendazole was 75.7 ± 4.61% and that of rapamycin was 98.0 ± 1.97%. In the clonogenic assay, M-FR was 6.9 times more effective than that free fenbendazole/rapamycin. The in vitro drug release profile showed slower release in the combination formulation than in the single formulation. There was no toxicity, and tumor growth was suppressed substantially by our formulation compared with that seen with the control. The findings of our study lay a foundation for using fenbendazole and rapamycin for OC treatment.”

Video: https://youtu.be/CUbXxnGHjOQ

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles from pandemic-era hand-sanitizer manufacturing and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

PLGA-thiol From PolySciTech used in development of targeted nanoparticles for treatment of multi-drug resistant cancers

Wednesday, May 10, 2023, 3:57 PM ET

Doxorubicin and other drugs are commonly used as chemotherapy agents to treat cancer. However, several biochemical pathways including p-glycoprotein mediated pathways can lead to multi-drug resistance. These cancers can be targeted by their phosphatidylinositol-3-kinase (PI3K) to direct delivery of drugs to the cancers. Researchers at Chinese Academy of Sciences, Fujian Agriculture and Forestry University, and St. John's University utilized PLGA-SH (cat# AI025) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create multifunctional gold-polymer nanoparticles to deliver doxorubicin to cancer cells in a targeted manner. This research holds promise to provide for treatment of multi-drug resistant cancers. Read more: Lin, Ruikun, Lei Zhang, Biwei Ye, Yanan Wang, Yi-Dong Li, Hsu Jason, Wenzhen Liu et al. "A multi-functional nano-system combining PI3K-110α/β inhibitor overcomes P-glycoprotein mediated MDR and improves anti-cancer efficiency." Cancer Letters (2023): 216181. https://www.sciencedirect.com/science/article/pii/S0304383523001325

“Highlights: MDR limit chemotherapy against cancers, and nano-systems that can target P110α or P110β and inhibit MDR were not reported. BAY-1082439 can inhibit P110 subunits, attenuate P-gp-mediated MDR in cancers but is poorly soluble and unstable in blood. ·Here we constructed a multi-functional drug-loading nano-system PBDF for inhibiting the MDR KB cells overexpressing P-gp. BAY1082439@PLGA-SH, DOX@PLGA-SH NPs, and SH-PEG-FA were grafted to gold nanorods and PBDF was established. BBDF NPs inhibited proliferation of MDR KB-C2 cancer cells and KB-C2 tumor growth, and reduced metastasis of KB-C2 cells. Abstract: P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR) in cancers severely limit chemotherapeutic efficacy. We recently reported that phosphatidylinositol-3-kinase (PI3K) 110α and 110β subunits can be novel targets for reversal of P-gp mediated MDR in cancers, and BAY-1082439 as an inhibitor specific for PI3K 110α and 110β subunits could reverse P-gp-mediated MDR by downregulating P-gp expression in cancer cells. However, BAY-1082439 has very low solubility, short half-life and high in-vivo clearance rate. Till now, nano-system with the functions to target PI3K P110α and P110β and reverse P-gp mediated MDR in cancers has not been reported. In our study, a tumor targeting drug delivery nano-system PBDF was established, which comprised doxorubicin (DOX) and BAY-1082439 respectively encapsulated by biodegradable PLGA-SH nanoparticles (NPs) that were grafted to gold nanorods (Au NRs) modified with FA-PEG-SH, to enhance the efficacy to reverse P-gp mediated MDR and to target tumor cells, further, to enhance the efficiency to inhibit MDR tumors overexpressing P-gp. In-vitro experiments indicated that PBDF NPs greatly enhanced uptake of DOX, improved the activity to reverse MDR, inhibited the cell proliferation, and induced S-phase arrest and apoptosis in KB-C2 cells, as compared with free DOX combining free BAY-1082439. In-vivo experiments further demonstrated that PBDF NPs improved the anti-tumor ability of DOX and inhibited development of KB-C2 tumors. Notably, the metastasis of KB-C2 cells in livers and lungs of nude mice were inhibited by treatment with PBDF NPs, which showed no obvious in-vitro or in-vivo toxicity. Keywords: Multi-drug resistance (MDR) in cancer Phosphatidylinositol-3-kinase (PI3K) 110 subunits P-glycoprotein (P-gp/ABCB1) Multifunctional nano-system Tumor targeting”

Video: https://youtu.be/lQ3NAcGprCI

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles from pandemic-era hand-sanitizer manufacturing and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

PLGA-Maleimide from PolySciTech used in development of monocyte-targeting microparticles for use in Multiple Sclerosis treatment

Tuesday, May 9, 2023, 4:49 PM ET

One way to control drug delivery to specific locations is to affiliate the drug with cell type which traverses to that category so it can be carried along like the drugs are in a ‘backpack.’ This is particularly powerful for immune system treatment as immune cells provide for many opportunities of attachment based on signals and typically travel to sites of inflammation. Recently, researchers at Harvard University and Wyss Institute used PLGA-Maleimide (Cat# AI153) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create particles which surface adhere to monocytes and carry interleukin-4 and dexamethasone as immunomodulators. This research holds promise to provide treatment for Multiple sclerosis. Read more: Kapate, Neha, Michael Dunne, Ninad Kumbhojkar, Supriya Prakash, Lily Li-Wen Wang, Amanda Graveline, Kyung Soo Park et al. "A backpack-based myeloid cell therapy for multiple sclerosis." Proceedings of the National Academy of Sciences 120, no. 17 (2023): e2221535120. https://www.pnas.org/doi/abs/10.1073/pnas.2221535120

“Significance: Multiple sclerosis (MS) is a currently incurable autoimmune disease with a complex disease pathology. Despite the key role of myeloid cells in the pathophysiology of MS, current treatments do not specifically target myeloid cells or directly make their use for modulating the disease. We propose that immunomodulatory monocytes, upon intravenous injection, can infiltrate into inflamed central nervous system and have the potential to mitigate disease progression. We control monocyte phenotype through cell surface–adhered particles (“backpacks”) loaded with interleukin-4 and dexamethasone. Treatment with backpack-laden monocytes elicited local and systemic immunomodulatory effects, culminating in improved motor functions in experimental autoimmune encephalomyelitis mice. The results reported here demonstrate the possibility of myeloid cells as a therapy and drug target in MS. Abstract: Multiple sclerosis (MS) is an incurable autoimmune disease and is currently treated by systemic immunosuppressants with off-target side effects. Although aberrant myeloid function is often observed in MS plaques in the central nervous system (CNS), the role of myeloid cells in therapeutic intervention is currently overlooked. Here, we developed a myeloid cell-based strategy to reduce the disease burden in experimental autoimmune encephalomyelitis (EAE), a mouse model of progressive MS. We developed monocyte-adhered microparticles (“backpacks”) for activating myeloid cell phenotype to an anti-inflammatory state through localized interleukin-4 and dexamethasone signals. We demonstrate that backpack-laden monocytes infiltrated into the inflamed CNS and modulated both the local and systemic immune responses. Within the CNS, backpack-carrying monocytes regulated both the infiltrating and tissue-resident myeloid cell compartments in the spinal cord for functions related to antigen presentation and reactive species production. Treatment with backpack-monocytes also decreased the level of systemic pro-inflammatory cytokines. Additionally, backpack-laden monocytes induced modulatory effects on TH1 and TH17 populations in the spinal cord and blood, demonstrating cross talk between the myeloid and lymphoid arms of disease. Backpack-carrying monocytes conferred therapeutic benefit in EAE mice, as quantified by improved motor function. The use of backpack-laden monocytes offers an antigen-free, biomaterial-based approach to precisely tune cell phenotype in vivo, demonstrating the utility of myeloid cells as a therapeutic modality and target.”

Video: https://youtu.be/OnndlGtOfKY

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles from pandemic-era hand-sanitizer manufacturing and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

PEG-PLA from PolySciTech used in development of nanoparticles for brain cancer treatment

Thursday, April 27, 2023, 4:46 PM ET

PEG-PLA from PolySciTech used in development of nanoparticles for brain cancer treatment

Glioblastoma is a fast-growing and aggressive brain tumor that invades the nearby brain tissue. Treatment of it is made more difficult by the sensitivity of the area in which it is present and poor drug delivery across the blood-brain-barrier. Researchers at Harvard Medical School, Brown University, Phosphorex, Inc., Cytodigm, Inc. used PEG-PLA (AK031) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles loaded with 6-bromoindirubin-3′-acetoxime for treatment of brain cancer. This research holds promise to improve treatment of this lethal disease. Read more: Zdioruk, Mykola, Jorge-Luis Jimenez-Macias, Michal Oskar Nowicki, Katherine E. Manz, Kurt D. Pennell, Marilin S. Koch, Tomer Finkelberg et al. "PPRX-1701, a nanoparticle formulation of 6′-bromoindirubin acetoxime, improves delivery and shows efficacy in preclinical GBM models." Cell Reports Medicine (2023). https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(23)00129-5.pdf

“Highlights: PPRX-1701 is a deliverable formulation of 6-bromoindirubin-3′-acetoxime (BiA). Inhibits IDO1 expression and increases CD8 T cell infiltration in GBM mouse models. Data support investigation of this approach for future potential translation. Summary: Derivatives of the Chinese traditional medicine indirubin have shown potential for the treatment of cancer through a range of mechanisms. This study investigates the impact of 6′-bromoindirubin-3′-acetoxime (BiA) on immunosuppressive mechanisms in glioblastoma (GBM) and evaluates the efficacy of a BiA nanoparticle formulation, PPRX-1701, in immunocompetent mouse GBM models. Transcriptomic studies reveal that BiA downregulates immune-related genes, including indoleamine 2,3-dioxygenase 1 (IDO1), a critical enzyme in the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) immunosuppressive pathway in tumor cells. BiA blocks interferon-γ (IFNγ)-induced IDO1 protein expression in vitro and enhances T cell-mediated tumor cell killing in GBM stem-like cell co-culture models. PPRX-1701 reaches intracranial murine GBM and significantly improves survival in immunocompetent GBM models in vivo. Our results indicate that BiA improves survival in murine GBM models via effects on important immunotherapeutic targets in GBM and that it can be delivered efficiently via PPRX-1701, a nanoparticle injectable formulation of BiA. Keywords: glioblastoma 6-bromoindirubin-3′-acetoxime indoleamine-pyrrole 2,3-dioxygenase IDO1 tumor microenvironment”

Video: https://youtu.be/vR6bPOwY7QM

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles from pandemic-era hand-sanitizer manufacturing and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

PEG-PLGA from Akina, Inc. used in development of cancer research methodologies using 3D Cell Culture

Friday, April 14, 2023, 4:36 PM ET

In addition to science development of technology and products that improve human lives, scientific development is also required to the process of how development is done. One example is cancer therapy development, which requires processes that can determine whether a prototype treatment is safe and effective before going into a human, clinical setting. Researchers at The University of Adelaide and The University of Queensland (Australia) used PEG-PLGA (AK026) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescent nanoparticles for testing the diffusivity properties of tumor spheroids grown on various test biomechanical gels. This research holds promise to improve the way in which cancer therapies are developed in the future. Read more: Cameron, Anna P., Song Gao, Yun Liu, and Chun-Xia Zhao. "Impact of hydrogel biophysical properties on tumor spheroid growth and drug response." Biomaterials Advances (2023): 213421. https://www.sciencedirect.com/science/article/pii/S2772950823001449

“Highlights: Effect of biophysical attributes of hydrogels on tumor growth and drug response. Characterization of complex modulus, loss tangent, permeability and pore size of hydrogels. Effect of hydrogel concentration on migratory growth of tumor spheroids. Different drug response of spheroids in ECMs with different concentration of hydrogels. Abstract: The extracellular matrix (ECM) plays a critical role in regulating cell-matrix interactions during tumor progression. These interactions are due in large part to the biophysical properties responding to cancer cell interactions. Within in vitro models, the ECM is mimicked by hydrogels, which possess adjustable biophysical properties that are integral to tumor development. This work presents a systematic and comparative study on the impact of the biophysical properties of two widely used natural hydrogels, Matrigel and collagen gel, on tumor growth and drug response. The biophysical properties of Matrigel and collagen including complex modulus, loss tangent, diffusive permeability, and pore size, were characterized. Then the spheroid growth rates in these two hydrogels were monitored for spheroids with two different sizes (140 μm and 500 μm in diameters). An increased migratory growth was observed in the lower concentration of both the gels. The effect of spheroid incorporation within the hydrogel had a minimal impact on the hydrogel's complex modulus. Finally, 3D tumor models using different concentrations of hydrogels were applied for drug treatment using paclitaxel. Spheroids cultured in hydrogels with different concentrations showed different drug response, demonstrating the significant effect of the choice of hydrogels and their concentrations on the drug response results despite using the same spheroids. This study provides useful insights into the effect of hydrogel biophysical properties on spheroid growth and drug response and highlights the importance of hydrogel selection and in vitro model design. Keywords: Hydrogel Spheroid Extracellular matrix Biophysical properties Cancer Drug response”

Video: https://youtu.be/CDxOtdfpIoo

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles from pandemic-era hand-sanitizer manufacturing and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

mPEG-PCL from PolySciTech used in development of a dual-drug loaded nanoparticle for ovarian cancer therapy

Friday, April 14, 2023, 4:35 PM ET

Ovarian cancer can be fatal as it is difficult to detect at an early stage leading to more than 70% of ovarian cancers being stage 3 or higher at diagnosis. Typical treatment involves surgery and chemotherapy. Paclitaxel is commonly used however cancers can grow resistant to it requiring the use of a secondary drug. Researchers at Chungbuk National University and Sookmyung Women’s University (Korea) used mPEG-PCL (cat# AK073) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create dual-loaded nanoparticles (paclitaxel and sorafenib) for ovarian cancer treatment. This research holds promise to improve ovarian cancer therapies in the future. Read more: Jin, Chae Eun, Moon Sup Yoon, Min Jeong Jo, Seo Yeon Kim, Jae Min Lee, Su Jeong Kang, Chun-Woong Park, Jin-Seok Kim, and Dae Hwan Shin. "Synergistic Encapsulation of Paclitaxel and Sorafenib by Methoxy Poly (Ethylene Glycol)-b-poly (caprolactone) Polymeric Micelles for Ovarian Cancer Therapy." Pharmaceutics 15, no. 4 (2023): 1206. https://www.mdpi.com/1999-4923/15/4/1206

“Abstract: Ovarian cancer has a high mortality rate due to difficult detection at an early stage. It is necessary to develop a novel anticancer treatment that demonstrates improved efficacy while reducing toxicity. Here, using the freeze-drying method, micelles encapsulating paclitaxel (PTX) and sorafenib (SRF) with various polymers were prepared, and the optimal polymer (mPEG-b-PCL) was selected by measuring drug loading (%), encapsulation efficiency (%), particle size, polydispersity index, and zeta potential. The final formulation was selected based on a molar ratio (PTX:SRF = 1:2.3) with synergistic effects on two ovarian cancer cell lines (SKOV3-red-fluc, HeyA8). In the in vitro release assay, PTX/SRF micelles showed a slower release than PTX and SRF single micelles. In pharmacokinetic evaluation, PTX/SRF micelles showed improved bioavailability compared to PTX/SRF solution. In in vivo toxicity assays, no significant differences were observed in body weight between the micellar formulation and the control group. The anticancer effect of PTX/SRF combination therapy was improved compared to the use of a single drug. In the xenografted BALB/c mouse model, the tumor growth inhibition rate of PTX/SRF micelles was 90.44%. Accordingly, PTX/SRF micelles showed improved anticancer effects compared to single-drug therapy in ovarian cancer (SKOV3-red-fluc). Keywords: ovarian cancer; paclitaxel; sorafenib; combination therapy; mPEG-b-PCL; micelle; antitumor; pharmacokinetics”

Video: https://youtu.be/Hg9ti-OdOSs

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles from pandemic-era hand-sanitizer manufacturing and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

PLGA-PEG-PLGA from PolySciTech used in development of topical cream for skin-cancer treatment

Friday, April 14, 2023, 4:34 PM ET

Melanoma is a form of skin cancer which can be treated in early stages by localized delivery of chemotherapy agents to the skin. Researchers at St. John’s University and OncoGone, Inc. used thermogelling PLGA-PEG-PLGA (AK012 and AK019) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create thermally sensitive nanogels for delivery of paclitaxel (PTX) and temozolomide (TMZ) as melanoma treatment. This research holds promise to improve therapy against skin cancer. Read more: Rahman, Sadia, Tasmima N. Haque, Vrashabh V. Sugandhi, Aishwarya L. Saraswat, Xiaoban Xin, and Hyunah Cho. "Topical Cream Carrying Drug-Loaded Nanogels for Melanoma Treatment." Pharmaceutical Research (2023): 1-11. https://link.springer.com/article/10.1007/s11095-023-03506-z

“Abstract: In this study, nanogel creams carrying paclitaxel (PTX) and temozolomide (TMZ) were prepared for the topical treatment of melanoma. PTX and TMZ were first loaded in poly-(D,L-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLAG-b-PEG-b-PLGA) thermosensitive nanogels, which made a transition from a free-flowing sol (formation of micellar network) at 25°C with the z-average particle size of c.a. 96 nm to a gel (aggregation of micelles) at 33°C with the z-average particle size of c.a. 427 nm. An anhydrous absorption ointment base, aquaphor, was then added to drug-loaded nanogels to form nanogel creams carrying PTX and TMZ. Nanogel creams permitted controlled release of the payloads and improved the penetration of the payloads through the rodent skin compared to drug(s)-loaded nanogels. PTX and TMZ in a combination were synergistically effective in inhibiting SK-MEL28, A375, and B16-F10 melanoma cancer cells in vitro. Topically applied nanogel creams carrying TMZ/PTX (4 mg/1.5 mg/dose) showed a trend of tumor volume inhibition on B16-F10-bearing xenograft mice in vivo.”

Video: https://youtu.be/m3YxnU8SGnk

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Bulk, empty bottles from pandemic-era hand-sanitizer manufacturing and other excess inventory items are available for purchase from Akina, Inc. See more here: https://akinainc.com/polyscitech/YardSale/

Tuesday, April 11, 2023, 4:39 PM ET

PLGA-PEG-COOH from PolySciTech used in research on nanoparticle drug delivery in neonatal patients

The same kind of medicinal approaches used in adults do not always work the same in children or infants due to physiological and metabolic differences which slowly develop with age. For this reason, it is important for pharmaceutical delivery strategies and medicines to be developed specifically for use in pediatric and neonatal populations. Researchers at University of Washington used PLGA-PEG-COOH (cat# AI107) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles and investigated the pharmacokinetics and pharmacodynamics of nanoparticulate drug-delivery systems in young populations. This research holds promise to provide for improved delivery of pharmaceutics in young populations. Read more: Xu, Nuo, Megan Wong, Gabrielle Balistreri, and Elizabeth Nance. "Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant." Pharmaceutics 15, no. 4 (2023): 1176. https://www.mdpi.com/1999-4923/15/4/1176

“Abstract: The development of therapeutics for pediatric use has advanced in the last few decades, yet the off-label use of adult medications in pediatrics remains a significant clinical problem. Nano-based medicines are important drug delivery systems that can improve the bioavailability of a range of therapeutics. However, the use of nano-based medicines for application in pediatric populations is challenged by the lack of pharmacokinetic (PK) data in this population. To address this data gap, we investigated the PK of polymer-based nanoparticles in term-equivalent neonatal rats. We used poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles, which are polymer nanoparticles that have been extensively studied in adult populations but less commonly applied in neonates and pediatrics. We quantified the PK parameters and biodistribution of PLGA-PEG nanoparticles in term-equivalent healthy rats and revealed the PK and biodistribution of polymeric nanoparticles in neonatal rats. We further explored the effects of surfactant used to stabilize PLGA-PEG particles on PK and biodistribution. We showed that 4 h post intraperitoneal injection, nanoparticles had the highest accumulation in serum, at 54.0% of the injected dose for particles with Pluronic® F127 (F127) as the stabilizer and at 54.6% of the injected dose for particles with Poloxamer 188 (P80) as the stabilizer. The half-life of the F127-formulated PLGA-PEG particles was 5.9 h, which was significantly longer than the 1.7 h half-life of P80-formulated PLGA-PEG particles. Among all organs, the liver had the highest nanoparticle accumulation. At 24 h after administration, the accumulation of F127-formulated PLGA-PEG particles was at 26.2% of the injected dose, and the accumulation of P80-formulated particles was at 24.1% of the injected dose. Less than 1% of the injected nanoparticles was observed in healthy rat brain for both F127- and P80-formulated particles. These PK data inform the use of polymer nanoparticle applications in the neonate and provide a foundation for the translation of polymer nanoparticles for drug delivery in pediatric populations. Keywords: nanomedicine; pediatrics; drug delivery; half-life; nanoparticle accumulation; clinical translation”

Video: https://youtu.be/sO1YQ0zpbJU

Akina Inc. is now hiring both Staff Scientist and Laboratory Intern. See more here: http://akinainc.com/employment.php

Fluorescent PLGA-CY5 from PolySciTech used in development of anti-inflammatory drug delivery for arthritis treatment.

Monday, April 3, 2023, 4:18 PM ET

Rheumatoid arthritis, is an autoimmune and inflammatory disease where the immune system attacks healthy cells in the joints. One way to reduce the progress of arthritis is to reduce the inflammatory response at the location of the joint tissue to stop the immune attack. Researchers at University of California San Diego and University of Gothenburg (Sweden) used PLGA (cat# AP041) and PLGA-CY5 (cat# AV034) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescently stained PLGA microparticles to deliver anti-inflammatory trans retinoic acid to joint tissue. This research holds promise to improve therapies against arthritis in the future. Read more: McBride, David A., Matthew D. Kerr, Wade T. Johnson, Anders Nguyen, Martina Zoccheddu, Mina Yao, Edward B. Prideaux et al. "Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis." Advanced Science (2023): 2202720. https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202202720

“Abstract: Disease modifying antirheumatic drugs (DMARDs) have improved the prognosis of autoimmune inflammatory arthritides but a large fraction of patients display partial or nonresponsiveness to front-line DMARDs. Here, an immunoregulatory approach based on sustained joint-localized release of all-trans retinoic acid (ATRA), which modulates local immune activation and enhances disease-protective T cells and leads to systemic disease control is reported. ATRA imprints a unique chromatin landscape in T cells, which is associated with an enhancement in the differentiation of naïve T cells into anti-inflammatory regulatory T cells (Treg) and suppression of Treg destabilization. Sustained release poly-(lactic-co-glycolic) acid (PLGA)-based biodegradable microparticles encapsulating ATRA (PLGA-ATRA MP) are retained in arthritic mouse joints after intra-articular (IA) injection. IA PLGA-ATRA MP enhance migratory Treg which in turn reduce inflammation and modify disease in injected and uninjected joints, a phenotype that is also reproduced by IA injection of Treg. PLGA-ATRA MP reduce proteoglycan loss and bone erosions in the SKG and collagen-induced arthritis mouse models of autoimmune arthritis. Strikingly, systemic disease modulation by PLGA-ATRA MP is not associated with generalized immune suppression. PLGA-ATRA MP have the potential to be developed as a disease modifying agent for autoimmune arthritis.”

Video: https://youtu.be/XRirpeY8hPA

Akina Hiring Staff Scientist

Friday, March 31, 2023, 2:52 PM ET

Akina, Inc. is looking for a staff scientist to work on the research and development of biomedical, and pharmaceutical products and. The position is primarily formulations development, hydrogel research, and polymer chemistry. A bachelor’s degree in chemistry, biology, pharmaceutical sciences, biomedical engineering, or related scientific field is required. Prior work experience in research and development or pharmaceutical/biomedical field is a plus. Submit resume to General Manager, John Garner jg@akinainc.com

See more details here: http://akinainc.com/employment.php

PLGA from PolySciTech used in ocular antibiotic delivery system to prevent blindness due to ocular infections.

Friday, March 31, 2023, 2:51 PM ET

Bacterial Keratitis (BK) is the leading cause of ocular infections leading to blindness. Although antibiotic eyedrops can be used for treatment these tend to have poor drug delivery due to loss through tears and other factors. Using a formulation which adheres to the mucosal layer of the eye can drastically improve drug delivery. Researchers at Birla Institute of Technology & Science-Pilani and LV Prasad Eye Institute use PLGA (cat# AP040) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create PLGA-chitosan conjugate particles. They used these to deliver antibiotic, moxifloxacin, in a nanoparticle formulation to provide improved drug uptake. This research holds promise to prevent blindness by treating ocular infections. Read more: Ch, Sanjay, Sri Ganga Padaga, Balaram Ghosh, Sanhita Roy, and Swati Biswas. "Chitosan-poly (lactide-co-glycolide)/poloxamer mixed micelles as a mucoadhesive thermo-responsive moxifloxacin eye drop to improve treatment efficacy in bacterial keratitis." Carbohydrate Polymers (2023): 120822. https://www.sciencedirect.com/science/article/pii/S0144861723002874

“Abstract: A mucoadhesive self-assembling polymeric system was developed to carry moxifloxacin (M) for treating bacterial keratitis (BK). Chitosan-PLGA (C) conjugate was synthesized, and poloxamers (F68/127) were mixed in different proportions (1: 5/10) to prepare moxifloxacin (M)-encapsulated mixed micelles (M@CF68/127(5/10)Ms), including M@CF68(5)Ms, M@CF68(10)Ms, M@CF127(5)Ms, and M@CF127(10)Ms. The corneal penetration and mucoadhesiveness were determined biochemically, in vitro using human corneal epithelial (HCE) cells in monolayers and spheroids, ex vivo using goat cornea, and in vivo via live-animal imaging. The antibacterial efficacy was studied on planktonic biofilms of P. aeruginosa and S. aureus (in vitro) and Bk-induced mice (in vivo). Both M@CF68(10)Ms and M@CF127(10)Ms demonstrated high cellular uptake, corneal retention, muco-adhesiveness, and antibacterial effect, with M@CF127(10)Ms exhibiting superior therapeutic effects in P. aeruginosa and S. aureus-infected BK mouse model by reducing the corneal bacterial load and preventing corneal damage. Therefore, the newly developed nanomedicine is promising for clinical translation in treating BK. Keywords: Chitosan Poloxamer Mixed micelles Bacterial keratitis Antibacterial Moxifloxacin”

Video: https://youtu.be/RngOUpdlpgE

Fluorescent PLGA-Rhodamine from PolySciTech used in development of dual-loaded nanoparticles for treatment of skin disease

Friday, March 31, 2023, 2:50 PM ET

Inflammatory Skin Conditions including eczema, seborrheic dermatitis, and psoriasis are extremely common and affect more than 27 million American adults. Ideally these can be treated using a localized or targeted therapy to reduce systemic side-effects. Researchers at Université Paris-Saclay, Université Paris-Cité, and Sorbonne Université (CNRS, Inserm, SFR-UMS-IPSIT) used PLGA-Rhodamine B (AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescently traceable nanoparticles for stabilizing an emulsion. This research holds promise to provide for dual-drug loaded formulations for treatment of skin diseases. Read more: Beladjine, Mohamed, Claire Albert, Maxime Sintès, Ghozlene Mekhloufi, Claire Gueutin, Valérie Nicolas, Alexis Canette et al. "Pickering Emulsions Stabilized With Biodegradable Nanoparticles For The Co-Encapsulation Of Two Active Pharmaceutical Ingredients." International Journal of Pharmaceutics (2023): 122870. https://www.sciencedirect.com/science/article/pii/S0378517323002909

“Abstract: Innovative Pickering emulsions co-encapsulating two active pharmaceutical ingredients (API) were formulated for a topical use. An immunosuppressive agent, either cyclosporine A (CysA) or tacrolimus (TAC), was encapsulated at high drug loading in biodegradable and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). These NP stabilized the oil droplets (Miglyol) containing an anti-inflammatory drug, calcitriol (CAL). The influence of the API on the physico-chemical properties of these emulsions were studied. Emulsions formulated with or without API had a similar macroscopic and microscopic structure, as well as interfacial properties, and they exhibited a good stability for at least 55 days. The emulsions did not alter the viability of human keratinocytes (HaCaT cell line) after 2 and 5 days of exposure to NP concentrations equivalent to efficient API dosages. Thus, these new Pickering emulsions appear as a promising multidrug delivery system for the treatment of chronical inflammatory skin diseases. Keywords: calcitriol co-encapsulation cyclosporine A interfacial properties nanoparticles Pickering emulsion PLGA tacrolimus skin diseases stability”

Video: https://youtu.be/aSx24hHnbdA

Akina, Inc. Container Sale

Wednesday, March 29, 2023, 1:00 PM ET

Bulk, empty plastic bottles and caps useful for manufacturing of soaps, shampoos, conditioners, hand-sanitizer, sanitizing wipes, and other consumer products are being sold from Akina, Inc. from excess inventory. All items are available for pickup from Akina’s location (3495 Kent Avenue, West Lafayette, IN 47906) or may be shipped with additional costs for shipping fees. If interested, contact Akina Sales at sales@akinainc.com or 765-464-0501 for purchasing or more information.

Description (A)



8 oz clear PET Boston Round with black flip-top cap (24/410) (Box 50)

$ 22.00


8 oz clear PET Boston Round with black flip-top cap (24/410) (Box 60)

$ 27.00


8 oz clear PET Boston Round with black flip-top cap (24/410) (189 Box)

$ 85.00


Description (B)



8 oz HDPE Pump-top bottle (Box of 21)

$ 17.00


8 oz HDPE Pump-top bottle (Box of 66)

$ 53.00


8 oz HDPE Pump-top bottle (Box of 71)

$ 57.00


Description (C)



8 oz LDPE Pump-top bottle (box of 195 bottles)

$ 150.00


Description (D)



Natural PP bottle 8 oz, flip-cap (Box of 80)

$ 120.00


Description (E)



Cannisters (kit of 12: including 12 bottoms, tops, and Dutch Harbor plant-based wipes inserts (50 ct))

$ 85.00


Description (F)



24/410 cap natural, clear flip-top (Box of 670)

$ 250.00


Description (G)



White PP plastic 24-410 spouted dispensing lid (Box of 1635)

$ 350.00


PLGA-PEG-PLGA from PolySciTech used in development of thermogel for treatment of corneal injuries.

Wednesday, March 22, 2023, 4:35 PM ET

Even relatively minor ocular injuries can lead to downstream blindness due to localized inflammation and overgrowth of blood vessels occurring in response to the injury. This result can be prevented by TNF and VEGF inhibitors however this requires consistent application of the drugs during the healing process. Researchers at Harvard Medical School, Massachusetts Eye and Ear Infirmary, and University of New Mexico School of Medicine utilized PLGA-PEG-PLGA (AK141) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a thermogel for long-acting delivery of adalimumab and aflibercept for ocular injection. This research holds promise to reduce the incidence of blindness by offering a new option for treatment of ocular damage. Read more: Zhou, Chengxin, Fengyang Lei, Pui-Chuen Hui, Natalie Wolkow, Claes Dohlman, Demetrios G. Vavvas, James Chodosh, and Eleftherios I. Paschalis. "A novel sustained release therapy of combined VEGF and TNF-α inhibitors leads to pan-ocular protection for months after severe ocular trauma." bioRxiv (2023): 2023-03. https://www.biorxiv.org/content/10.1101/2023.03.14.531626.abstract

“Purpose: To develop a clinically feasible and practical therapy for multi-ocular protection following ocular injury by using a thermosensitive drug delivery system (DDS) for sustained delivery of TNF-alpha and VEGF inhibitors to the eye. Methods: A thermosensitive, biodegradable hydrogel DDS (PLGA-PEG-PLGA triblock polymer) loaded with 0.7mg of adalimumab and 1.4 mg of aflibercept was injected subconjunctivally in Dutch-belted pigmented rabbits after corneal alkali injury. The polymer was tuned to transition from liquid to gel upon contact with body temperature without need of a catalyst. Control rabbits received 2mg of IgG loaded DDS or 1.4mg aflibercept loaded DDS. Animals were followed for 3 months and assessed for tolerability and prevention of corneal neovascularization (NV), improvement of corneal re-epithelialization, inhibition of retinal ganglion cell (RGC) and optic nerve axon loss, and inhibition of immune cell infiltration into the cornea. Drug release kinetics was assessed in vivo using aqueous humor protein analysis. Results: A single subconjunctival administration of dual anti-TNF-alpha/anti-VEGF DDS achieved sustained 3-month delivery of antibodies to the anterior chamber, iris, ciliary body, and retina. Administration after corneal alkali burn suppressed CD45+ immune cell infiltration into the cornea, completely inhibited cornea NV for 3 months, accelerated corneal re-epithelialization and wound healing, and prevented RGC and optic nerve axon loss at 3 months. In contrast, anti-VEGF alone or IgG DDS treatment led to persistent corneal epithelial defect, increased infiltration of CD45+ immune cells into the cornea, and significant loss of RGCs and optic nerve axons at 3 months. Aqueous humor protein analysis showed first-order release kinetics without adverse effects at the injection site. Conclusion: Sustained concomitant inhibition of TNF-alpha and VEGF using a biodegradable, slow-release thermosensitive DDS provides significant ocular protection and prevents corneal neovascularization and irreversible damage to retina and optic nerve after corneal alkali injury. This therapeutic approach has the potential to dramatically improve the outcomes of severe ocular injuries in patients.”

Video: https://youtu.be/l9PyjfDNJAk

PLCL from PolySciTech used in development of heart valve replacement for tissue engineering

Monday, February 27, 2023, 2:46 PM ET

Tissue engineering is a process where a cell scaffold or other structure is provided to allow for damaged or missing parts of the human body to regrow. The bioresorbable scaffold should match the mechanical properties of the tissue to be replaced as well as provide a surface for cells to attach to and grow on. Researchers at University of Missouri used PLCLs with a range of LA:CL ratios (cat# AP147, AP015, AP151, AP262) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a mechanically robust and elastic heart valve replacement. This research holds promise to regrow or replace damaged portions of heart tissue. Read more: Snyder, Yuriy, and Soumen Jana. "Elastomeric Trilayer Substrates with Native-like Mechanical Properties for Heart Valve Leaflet Tissue Engineering." ACS Biomaterials Science & Engineering (2023). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.2c01430

“Heart valve leaflets have a complex trilayered structure with layer-specific orientations, anisotropic tensile properties, and elastomeric characteristics that are difficult to mimic collectively. Previously, trilayer leaflet substrates intended for heart valve tissue engineering were developed with nonelastomeric biomaterials that cannot deliver native-like mechanical properties. In this study, by electrospinning polycaprolactone (PCL) polymer and poly(l-lactide-co-ε-caprolactone) (PLCL) copolymer, we created elastomeric trilayer PCL/PLCL leaflet substrates with native-like tensile, flexural, and anisotropic properties and compared them with trilayer PCL leaflet substrates (as control) to find their effectiveness in heart valve leaflet tissue engineering. These substrates were seeded with porcine valvular interstitial cells (PVICs) and cultured for 1 month in static conditions to produce cell-cultured constructs. The PCL/PLCL substrates had lower crystallinity and hydrophobicity but higher anisotropy and flexibility than PCL leaflet substrates. These attributes contributed to more significant cell proliferation, infiltration, extracellular matrix production, and superior gene expression in the PCL/PLCL cell-cultured constructs than in the PCL cell-cultured constructs. Further, the PCL/PLCL constructs showed better resistance to calcification than PCL constructs. Trilayer PCL/PLCL leaflet substrates with native-like mechanical and flexural properties could significantly improve heart valve tissue engineering. KEYWORDS: elastomer electrospinning trilayer tissue engineering heart valve leaflet calcification”

Video: https://youtu.be/sO_s_RNSTJ8

Thermogelling PLGA-PEG-PLGA from PolySciTech used in research on preventing cardiovascular restenosis

Monday, February 27, 2023, 10:01 AM ET

Cardiovascular disease is the leading cause of all deaths worldwide. Restenosis is the re-narrowing of a blood vessel after catheterization and can lead to down-stream heart problems even after surgical intervention. Researchers at University of Virginia used PLGA-PEG-PLGA (cat# AK012) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a thermogelling delivery vehicle for EED226 to deliver it in place in the periadventitial space of the injured artery and observe its effects. This research holds promise to further understand and prevent in-stent restenosis. Read more: Zhang, Mengxue, Jing Li, Qingwei Wang, Go Urabe, Runze Tang, Yitao Huang, Jose Verdezoto Mosquera et al. "Gene-repressing epigenetic reader EED unexpectedly enhances cyclinD1 gene activation." Molecular Therapy-Nucleic Acids (2023). https://www.cell.com/molecular-therapy-family/nucleic-acids/pdf/S2162-2531(23)00044-6.pdf

“Epigenetically switched, proliferative vascular smooth muscle cells (SMCs) form neointima, engendering stenotic diseases. Histone-3 lysine-27 trimethylation (H3K27me3) and acetylation (H3K27ac) marks are associated with gene repression and activation, respectively. The polycomb protein embryonic ectoderm development (EED) reads H3K27me3 and also enhances its deposition, hence a canonical gene-repressor. However, herein we found an unexpected role for EED in activating the bona fide pro-proliferative gene Ccnd1 (cyclinD1). EED overexpression in SMCs increased Ccnd1 mRNA, seemingly contradicting its gene-repressing function. Yet consistently, EED co-immunoprecipitated with gene-activating H3K27ac reader BRD4, and they co-occupied at both mitogen-activated Ccnd1 and mitogen-repressed P57 (bona fide anti-proliferative gene), as indicated by chromatin immunoprecipitation-qPCR. These results were abolished by an inhibitor of either the EED/H3K27me3 or BRD4/H3K27ac reader function. In accordance, elevating BRD4 increased H3K27me3. In vivo, while EED was upregulated in rat and human neointimal lesions, selective EED inhibition abated angioplasty-induced neointima and reduced cyclinD1 in rat carotid arteries. Thus, results uncover a previously unknown role of EED in Ccnd1 activation, likely via its cooperativity with BRD4 that enhances each other’s reader function, i.e. activating pro-proliferative Ccnd1 while repressing anti-proliferative P57. As such, this study confers mechanistic implications for the epigenetic intervention of neointimal pathology.”

Video: https://youtu.be/9_6b6nn1MR0

PLGA-PEG-Mal, PLGA-PEG from PolySciTech used in development of cancer diagnosing nanobubbles

Monday, February 27, 2023, 10:00 AM ET

Ultrasound is a widely applicable and robust imaging technique that can determine internal features of humans in a non-invasive manner. One way to assist clinicians in treating cancer is to render the tumors visible by ultrasound so that they can be readily diagnosed and identified. Researchers at University of Illinois Urbana-Champaign Used PLGA (cat# AP154) as well as PLGA-PEG, and PLGA-PEG-Mal from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create targeted nanoparticles loaded with fluorescent dye and ultrasound contrast agent which attach to prostate cancer by ligand binding. This research holds promise to improve diagnostic techniques for treatment of cancer. Read More: Zhao, Shensheng, Leanne Lee, Yang Zhao, N. Liang, and Y. Chen. "Photoacoustic signal enhancement in dual-contrast gastrin-releasing peptide receptor-targeted nanobubbles." Frontiers in Bioengineering and Biotechnology 11 (2023). https://europepmc.org/article/pmc/pmc9887164

“Translatable imaging agents are a crucial element of successful molecular imaging. Photoacoustic molecular imaging relies on optical absorbing materials to generate a sufficient signal. However, few materials approved for human use can generate adequate photoacoustic responses. Here we report a new nanoengineering approach to further improve photoacoustic response from biocompatible materials. Our study shows that when optical absorbers are incorporated into the shell of a gaseous nanobubble, their photoacoustic signal can be significantly enhanced compared to the original form. As an example, we constructed nanobubbles using biocompatible indocyanine green (ICG) and biodegradable poly(lactic-co-glycolic acid) (PLGA). We demonstrated that these ICG nanobubbles generate a strong ultrasound signal and almost four-fold photoacoustic signal compared to the same concentration of ICG solution; our theoretical calculations corroborate this effect and elucidate the origin of the photoacoustic enhancement. To demonstrate their molecular imaging performance, we conjugated gastrin-releasing peptide receptor (GRPR) targeting ligands with the ICG nanobubbles. Our dual photoacoustic/ultrasound molecular imaging shows a more than three-fold enhancement in targeting specificity of the GRPR-targeted ICG nanobubbles, compared to untargeted nanobubbles or prostate cancer cells not expressing GRPR, in a prostate cancer xenograft mouse model in vivo. Keywords: cancer diagnosis, photoacoustic, ultrasound, molecular imaging, multimodal imaging, nanobubbles, GRPR, ICG”

Video: https://youtu.be/nXRUeyuLsoI

Fluorescent PLGA from PolySciTech used in Development of nanoparticles for pancreatic cancer therapy

Friday, February 24, 2023, 2:54 PM ET

Pancreatic cancer is very difficult to treat and remains the leading cause of cancer-related deaths. Researchers at The Hebrew University of Jerusalem utilized PLGA-CY5 (cat# AV034) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescently traceable nanoparticles. They used these for testing the uptake of SiRNA loaded nanoparticles towards pancreatic cancer. This research holds promise to improve therapy against this fatal disease. Read More: Agbaria, Majd, Doaa Jbara-Agbaria, Etty Grad, Meital Ben-David-Naim, Gil Aizik, and Gershon Golomb. "Nanoparticles of VAV1 siRNA combined with LL37 peptide for the treatment of pancreatic cancer." Journal of Controlled Release 355 (2023): 312-326. https://www.sciencedirect.com/science/article/pii/S0168365923000937

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer-related death, and it is highly resistant to therapy owing to its unique extracellular matrix. VAV1 protein, overexpressed in several cancer diseases including pancreatic cancer (PC), increases tumor proliferation and enhances metastases formation, which are associated with decreased survival. We hypothesized that an additive anti-tumor effect could be obtained by co-encapsulating in PLGA nanoparticles (NPs), the negatively charged siRNA against VAV1 (siVAV1) with the positively charged anti-tumor LL37 peptide, as a counter-ion. Several types of NPs were formulated and were characterized for their physicochemical properties, cellular internalization, and bioactivity in vitro. NPs' biodistribution, toxicity, and bioactivity were examined in a mice PDAC model. An optimal siVAV1 formulation (siVAV1-LL37 NPs) was characterized with desirable physicochemical properties in terms of nano-size, low polydispersity index (PDI), neutral surface charge, high siVAV1 encapsulation efficiency, spherical shape, and long-term shelf-life stability. Cell assays demonstrated rapid engulfment by PC cells, a specific and significant dose-dependent proliferation inhibition, as well as knockdown of VAV1 mRNA levels and migration inhibition in VAV1+ cells. Treatment with siVAV1-LL37 NPs in the mice PDAC model revealed marked accumulation of NPs in the liver and in the tumor, resulting in an increased survival rate following suppression of tumor growth and metastases, mediated via the knockdown of both VAV1 mRNA and protein levels. This proof-of-concept study validates our hypothesis of an additive effect in the treatment of PC facilitated by co-encapsulating siVAV1 in NPs with LL37 serving a dual role as a counter ion as well as an anti-tumor agent.

Video: https://youtu.be/RdZzFuErcbk

PLGA-PEG-Mal from PolySciTech used in development of peptide-based nanoparticle treatment of prostate cancer

Wednesday, February 22, 2023, 1:39 PM ET

Prostate cancer is the second most prevalent cause of cancer deaths in males, worldwide. There are many therapies available, however most patients with metastatic prostate cancer suffer relapse. Researchers at Barcelona Institute of Science and Technology, Institute for Advanced Chemistry of Catalonia (Spain), and Eindhoven University of Technology (Netherlands) used PLGA-PEG-Maleimide (cat# AI110) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to conjugate on WQP, a targeting peptide. They created nanoparticles and tested their ability to target towards prostate cells and provide treatment for prostate cancer. This research holds promise to improve therapy against prostate cancer in the future. Read More: Murar, Madhura, Silvia Pujals, and Lorenzo Albertazzi. "Multivalent effect of peptide functionalized polymeric nanoparticles towards selective prostate cancer targeting." Nanoscale Advances (2023). https://pubs.rsc.org/en/content/articlehtml/2023/na/d2na00601d

“The concept of selective tumor targeting using nanomedicines has been around for decades; however, no targeted nanoparticle has yet reached the clinic. A key bottleneck is the non-selectivity of targeted nanomedicines in vivo, which is attributed to the lack of characterization of their surface properties, especially the ligand number, thereby calling for robust techniques that allow quantifiable outcomes for an optimal design. Multivalent interactions comprise multiple copies of ligands attached to scaffolds, allowing simultaneous binding to receptors, and they play an important role in targeting. As such, ‘multivalent’ nanoparticles facilitate simultaneous interaction of weak surface ligands with multiple target receptors resulting in higher avidity and enhanced cell selectivity. Therefore, the study of weak binding ligands for membrane-exposed biomarkers is crucial for the successful development of targeted nanomedicines. Here we carried out a study of a cell targeting peptide known as WQP having weak binding affinity for prostate specific membrane antigen, a known prostate cancer biomarker. We evaluated the effect of its multivalent targeting using polymeric NPs over its monomeric form on the cellular uptake in different prostate cancer cell lines. We developed a method of specific enzymatic digestion to quantify the number of WQPs on NPs having different surface valencies and observed that increasing valencies resulted in a higher cellular uptake of WQP-NPs over the peptide alone. We also found that WQP-NPs showed higher uptake in PSMA over-expressing cells, attributed to a stronger avidity for selective PSMA targeting. This kind of strategy can be useful for improving the binding affinity of a weak ligand as a means for selective tumor targeting.”

Video: https://youtu.be/nnzHrU3gjlw

PLGA from PolySciTech used in development of genipin modified sutures for surgical repair of tendons

Monday, February 20, 2023, 1:42 PM ET

Sutures mechanically hold tissue closed in place so that wounds or surgical incisions can heal. They can also provide a platform for drug release or bioactive surface which can have additional therapeutic effects. Researchers at Balgrist University Hospital, ETH Zurich, and Cantonal Hospital Lucerne used PLGA (AP081) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create coated genipin-coated sutures for tendon repair. They applied this modified suture to repairing tendons which typically do not heal well after injury. This research holds promise to improve surgical repairs for traumatic injuries. Read more: Götschi, Tobias, Anne-Gita Scheibler, Patrick Jaeger, Karl Wieser, Claude Holenstein, Jess G. Snedeker, and Roland S. Camenzind. "Improved suture pullout through genipin-coated sutures in human biceps tendons with spatially confined changes in cell viability." Clinical Biomechanics (2023): 105907. https://www.sciencedirect.com/science/article/pii/S0268003323000384

“Highlights: Suture cut-through is a common cause of rotator cuff repair failure. Coating the suture with collagen cross-linker enhances strength of suture-tendon interface. Short-term in vitro culturing reduces tenocyte viability near suture. No difference in cell viability between treatment groups at 3 mm + from suture. Abstract: The suture-tendon interface often constitutes the point of failure in tendon suture repair. In the present study, we investigated the mechanical benefit of coating the suture with a cross-linking agent to strengthen the nearby tissue after suture placement in human tendons and we assessed the biological implications regarding tendon cell survival in-vitro. Freshly harvested human biceps long head tendons were randomly allocated to control (n = 17) or intervention (n = 19) group. According to the assigned group, either an untreated or a genipin-coated suture was inserted into the tendon. 24 h after suturing, mechanical testing composed of cyclic and ramp-to-failure loading was performed. Additionally, 11 freshly harvested tendons were used for short-term in vitro cell viability assessment in response to genipin-loaded suture placement. These specimens were analyzed in a paired-sample setting as stained histological sections using combined fluorescent/light microscopy. Tendons stitched with a genipin-coated suture sustained higher forces to failure. Cyclic and ultimate displacement of the tendon-suture construct remained unaltered by the local tissue crosslinking. Tissue crosslinking resulted in significant cytotoxicity in the direct vicinity of the suture (<3 mm). At larger distances from the suture, however, no difference in cell viability between the test and the control group was discernable. The repair strength of a tendon-suture construct can be augmented by loading the suture with genipin. At this mechanically relevant dosage, crosslinking-induced cell death is confined to a radius of <3 mm from the suture in the short-term in-vitro setting. These promising results warrant further examination in-vivo. Keywords: Tendon Suture Soft tissue repair Collagen crosslinking Mechanical testing Cell viability”

Video: https://youtu.be/GWGbUs5gaF4

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.34228110313416 seconds)


Social Media

Facebook Twitter LinkedIn Google Blogger
Privacy Policy