Akinalytics
Polymer Blog
Technical Blog
John Garner, General ManagerA blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.
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PLGA-PEG-Maleimide from PolySciTech used to develop PLGA-PEG-DNA particles for immunomodulation applications
Thursday, September 21, 2023, 3:58 PM ET
DNA-scaffolded nanoparticles can be utilized to modify the behavior of human T-cells. One way to synthesize these is to react PLGA-PEG-Maleimide with thiolated DNA to provide for well controlled chemical synthesis. Researchers at University of California, San Francisco, University of California, Berkeley, Drexel University, and Brown University used PLGA-PEG-Maleimide (AI053) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create PLGA-PEG-DNA nanoparticles for immune cell modification. This research holds promise to provide for improvements in immunotherapy and other therapeutic applications in the future. Read more: Hadley, Pierce, Yuanzhou Chen, Lariana Cline, Zhiyuan Han, Qizhi Tang, Xiao Huang, and Tejal Desai. "Precise surface functionalization of PLGA particles for human T cell modulation." Protocol Exchange (2023). https://www.researchsquare.com/article/pex-2337/v1
“Abstract: Biofunctionalization of synthetic materials has broad utility in various biomedical applications but was limited by insufficient efficiency and controllability for bioconjugation. Therefore, we developed a new platform of building synthetic DNA-scaffolds on material surfaces to assemble and organize functional cargos, allowing for more precise control over cargo density and ratio. The adaptation of this technology for biomedical applications requires diverse expertise ranging from materials to bioconjugation chemistry to cell biology, and there are many critical checkpoints to ensure the quality of the platform for the expected biological function. In this protocol, we describe the three key fabrication procedures involved: 1) fabrication of polymeric particles engrafted with DNA-scaffolds (3 days), 2) attachment of functional cargos with complementary DNA strands (3-4 days), and 3) surface assembly control and quantification (<1 day). We have also provided additional experimental design considerations for modifying the platform—for example, varying the material composition, size, or cargo types—which may be required for different biological needs. An area of increasing interest is immunomodulation, where immune cells have been recognized for their ability to sense extracellular cues to shape their phenotypic adaptation. We have reported how their modulation can be advanced by this precision biomaterial platform. Here, we exemplify the protocol of primary human T cells activation and identified various parameters that can impact T cell ex vivo manufacturing. This protocol will equip investigators with the necessary fabrication procedures and validation assays to design high-fidelity DNA-scaffolded biomaterials for uses in diverse biomedical applications.”
PLGA-PEGs from PolySciTech used in development of high throughput nanoparticle development by machine learning
Thursday, September 14, 2023, 5:05 PM ET
Development and design of nanoparticle systems for drug delivery is a slow and labor intensive process consisting of significant amount of trial and error. This process can be streamlined by applying machine learning approach to optimize design based on trial results. Researchers at Eindhoven University of technology, and UMC Utrecht (Netherlands) used PLGA (#AP082), PLGA-PEG (#AK102), PLGA-PEG-COOH (#AI078), PLGA-PEG-NH2 (#AI189) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles for breast cancer treatment and to optimize their performance using machine-learning capabilities. This research holds promise to improve techniques for drug-delivery development field as a whole. Read more: Ortiz-Perez, Ana, Derek van Tilborg, Roy van der Meel, Francesca Grisoni, and Lorenzo Albertazzi. "Machine learning-guided high throughput nanoparticle design." (2023). https://chemrxiv.org/engage/chemrxiv/article-details/64eca19379853bbd789bf951
“Designing nanoparticles with desired properties is a challenging endeavor, due to the large combinatorial space and complex structure-function relationships. High throughput methodologies and machine learning approaches are attractive and emergent strategies to accelerate nanoparticle composition design. To date, how to combine nanoparticle formulation, screening, and computational decision-making into a single effective workflow is underexplored. In this study, we showcase the integration of three key technologies, namely microfluidic-based formulation, high content imaging, and active machine learning. As a case study, we apply our approach for designing PLGA-PEG nanoparticles with high uptake in human breast cancer cells. Starting from a small set of nanoparticles for model training, our approach led to an increase in uptake from ~5-fold to ~15-fold in only two machine learning guided iterations, taking one week each. To the best of our knowledge, this is the first time that these three technologies have been successfully integrated to optimize a biological response through nanoparticle composition. Our results underscore the potential of the proposed platform for rapid and unbiased nanoparticle optimization.”
PEG-PLGA from PolySciTech used in research on protein absorption effect on nanoparticle transport
Thursday, September 14, 2023, 5:04 PM ET
In physiologic conditions, nanoparticles naturally absorb biomolecules (proteins) onto their surface which affects their interactions with cells. The exact nature of the role this protein absorption plays is not fully understood. Researchers at University of Antioquia (Colombia), Max Planck Institute for Polymer Research, and Johannes Gutenberg University Mainz (Germany) used mPEG-PLGA (PolyVivo cat# AK037) and PLGA-PEG-COOH (PolyVivo cat# AI078) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to generate PEGylated and functionalized nanoparticles. These were used to investigate the transport behavior of antifungal agent and the interaction of these particles with macrophages. This research holds promise to improve therapeutic delivery techniques in the future. Read More: Mejía, Susana P., Richard da Costa Marques, Katharina Landfester, Jahir Orozco, and Volker Mailänder. "Effect of Protein Corona on The Specificity and Efficacy of Nanobioconjugates to Treat Intracellular Infections." Macromolecular Bioscience (2023): 2300197. https://onlinelibrary.wiley.com/doi/abs/10.1002/mabi.202300197
“Encapsulating drugs into functionalized nanoparticles (NPs) is an alternative to reach the specific therapeutic target with lower doses. However, when the NPs are in contact with physiological media, proteins adsorb on their surfaces, forming a protein corona (PC) biomolecular layer, acquiring a distinct biological identity that alters their interactions with cells. Itraconazole (ITZ), an antifungal agent, is encapsulated into PEGylated and/or functionalized NPs with high specificity for macrophages. It is evaluated how the PC impacts their cell uptake and antifungal effect. The minimum inhibitory concentration and colony-forming unit assays demonstrate that encapsulated ITZ into poly(ethylene glycol) (PEG) NPs improves the antifungal effect compared with NPs lacking PEGylation. The improvement can be related to the synergistic effect of the encapsulated ITZ and NPs composition and the reduction of PC formation in PEG NPs. Functionalized NPs with anti-F4/80 and anti-MARCO antibodies, or mannose without PEG and treated with PC, show an improved uptake but, in the presence of PEG, significantly reduce the endocytosis, dominating the stealth effect from PEG. Therefore, the PC plays a crucial role in the nanosystem uptake and antifungal effects, which suggests the need for in vivo model studies to evaluate the effect of PC in the specificity and biodistribution.”
PLGA from PolySciTech used in development of nanoparticle delivery system for treatment of congenital lysosomal disorders
Tuesday, August 29, 2023, 4:53 PM ET
Alterations in normal lysosomal function due to genetic disorders can lead to potentially lethal conditions. Researchers at Barcelona Institute for Science and Technology, University of Barcelona, University of Maryland, Autonomous University of Barcelona, and Institution of Catalonia for Research and Advanced Studies (Spain) used PLGA (AP083 and AP201) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles with controlled LA:GA ratio to study release of enzymes and behavior of the particles under lysosomal conditions. This research holds promise to provide for treatment of lysosomal and other disorders. Read more: del Moral, Maria, Maximilian Loeck, Eameema Muntimadugu, Guillem Vives, Vy Pham, Peter Pfeifer, Giuseppe Battaglia, and Silvia Muro. "Role of the Lactide: Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders." Journal of Functional Biomaterials 14, no. 9 (2023): 440. https://www.mdpi.com/2079-4983/14/9/440
“Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤−35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (<1 week) because of their smaller diameter, and 75:25 NPs did not destabilize in 4 weeks. All formulations presented burst release under lysosomal conditions (56–78% of the original load within 30 min), with 50:50 and 60:40 NPs releasing an additional small fraction after week 1. This provided 4 weeks of sustained catalytic activity, sufficient to fully degrade a substrate. Altogether, the 60:40 NP formulation is preferred given its higher EE, and 50:50 NPs represent a valid alternative, while the highest stability of 75:25 NPs may impair lysosomes. These results can guide future studies aiming to translate PLGA NP-based ERT for this and other LSDs. Keywords: lysosomal storage disorder; enzyme replacement therapy; hyaluronidase; poly(lactide-co-glycolide) nanoparticles; copolymer ratio; nanoparticle stability; enzyme release”
PCL from PolySciTech used in research and development of cell scaffold for bone tissue repair
Friday, August 25, 2023, 4:12 PM ET
Accidents, injuries or diseases such as cancer can lead to damaged or missing bone tissue. Bone tissue can be regrown using tissue engineering which involves providing a surface for cells to grow on and conditions amenable to growth. Researchers at Johns Hopkins University utilized PCL (AP009) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a porous scaffold for regrowth of bone tissue. This research holds promise to provide for treatment of damaged tissue. Read more: Singh, S., Zhou, Y., Farris, A.L., Whitehead, E.C., Nyberg, E.L., O'Sullivan, A.N., Zhang, N.Y., Rindone, A.N., Achebe, C.C., Zbijewski, W. and Grundy, W., 2023. Geometric Mismatch Promotes Anatomic Repair in Periorbital Bony Defects in Skeletally Mature Yucatan Minipigs. Advanced Healthcare Materials, p.2301944. https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202301944
“Abstract: Porous tissue-engineered 3D-printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect-specific geometry has long been considered an optimal strategy to restore pre-injury anatomy. However, studies in large animal models have revealed that biomaterial-induced bone formation largely occurs around the scaffold periphery. Such ectopic bone formation in the periorbital region can affect vision and cause disfigurement. To enhance anatomic reconstruction, geometric mismatches are introduced in the scaffolds used to treat full thickness zygomatic defects created bilaterally in adult Yucatan minipigs. 3D-printed, anatomically-mirrored scaffolds are used in combination with autologous stromal vascular fraction of cells (SVF) for treatment. An advanced image-registration workflow is developed to quantify the post-surgical geometric mismatch and correlate it with the spatial pattern of the regenerating bone. Osteoconductive bone growth on the dorsal and ventral aspect of the defect enhances scaffold integration with the native bone while medio-lateral bone growth leads to failure of the scaffolds to integrate. A strong positive correlation is found between geometric mismatch and orthotopic bone deposition at the defect site. The data suggest that strategic mismatch >20% could improve bone scaffold design to promote enhanced regeneration, osseointegration, and long-term scaffold survivability.”
PLGA-PEG-COOH from PolySciTech used in development of sialyl-Tn targeted drug-delivery system for treatment of gastric cancer
Monday, August 21, 2023, 3:16 PM ET
Gastric cancer is a disease in which a tumor forms within the stomach or gastric chambers and is the fourth leading cause of cancer-related deaths worldwide. Researchers at Universidade do Porto (Portugal) used PLGA-PEG-COOH (cat# AI076) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create Sialyl-Tn targeted nanoparticles for delivery of active pharmaceutical, Foretinib. This research holds promise to provide for improved therapy against gastric cancer in the future. Read more: Diniz, Francisca, Sofia Lamas, Hugo Osório, Paulo Aguiar, Daniela Freitas, Fátima Gartner, Bruno Sarmento, Celso A. Reis, and Joana Gomes. "Nanoparticles targeting Sialyl-Tn for efficient tyrosine kinase inhibitor delivery in gastric cancer." Acta Biomaterialia (2023). https://www.sciencedirect.com/science/article/pii/S1742706123004695
“Abstract: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide and, therefore, it is urgent to develop new and more efficient therapeutic approaches. Foretinib (FRT) is an oral multikinase inhibitor targeting MET (hepatocyte growth factor receptor) and RON (recepteur d'origine nantais) receptors tyrosine kinases (RTK) that has been used in clinical trials for several solid tumors. Targeted uptake of therapeutic polymeric nanoparticles (NPs) represents a powerful approach in cancer cell drug delivery. Previously, a nanodelivery system composed of polymeric NPs functionalized with B72.3 antibody, which targets the tumor-associated antigen Sialyl-Tn (STn), has been developed. Herein, these NPs were loaded with FRT to evaluate its capacity in delivering the drug to multicellular tumors spheroids (MCTS) and mouse models. The data indicated that B72.3 functionalized FRT-loaded PLGA-PEG-COOH NPs (NFB72.3) specifically target GC MCTS expressing the STn glycan (MKN45 SimpleCell (SC) cells), leading to a decrease in phospho RTK activation and reduced cell viability. In vivo evaluation using MKN45 SC xenograft mice revealed that NFB72.3 were able to decrease tumor growth, reduce cell proliferation and tumor necrosis. NFB72.3-treated tumors also showed inactivation of phospho-MET and RON. This study demonstrates the value of using NPs targeting STn for FRT delivery, highlighting its potential as a therapeutic application in GC.”
Thermogelling PLGA-PEG-PLGA used in developing a research tool to further understand ascending vaginal infections
Monday, August 21, 2023, 3:15 PM ET
Pre-term birth is commonly associated with bacterial infections in the vaginal tract which lead to inflammation and damage to both mother and fetus. Researchers at University College London, King’s College London, and Wits/SAMRC Antiviral Gene Therapy Research Unit (South Africa), used PLGA-PEG-PLGA (Cat# AK012) thermogel from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of developing a mouse-based disease model of ascending vaginal infection. This research provides a valuable tool to further evaluate therapeutic techniques against this common neonatal complication. Read more: Boyle, Ashley K., Konstantina Tetorou, Natalie Suff, Laura Beecroft, Margherita Mazzaschi, Mariya Hristova, Simon N. Waddington, and Donald Peebles. "Ascending vaginal infection in mice induces preterm birth and neonatal morbidity." bioRxiv (2023): 2023-08. https://www.biorxiv.org/content/10.1101/2023.08.14.553220.abstract
“Abstract: Preterm birth (PTB; delivery <37 weeks), the main cause of neonatal death worldwide, can lead to adverse neurodevelopmental outcomes, as well as lung and gut pathology. PTB is commonly associated with ascending vaginal infection. Previously, we have shown that ascending E. coli infection in pregnant mice induces PTB and reduces pup survival. Here, we demonstrate that this model recapitulates the pathology observed in human preterm neonates, namely neuroinflammation, lung injury and gut inflammation. In neonatal brains, there is widespread cell death, microglial activation, astrogliosis and reduced neuronal density. We also validate the utility of this model by assessing efficacy of maternal cervical gene therapy with an adeno-associated viral vector containing human beta defensin 3; this improves pup survival and reduces Tnfα mRNA expression in perinatal pup brains exposed to E. coli. This model provides a unique opportunity to evaluate the therapeutic benefit of preterm labour interventions on perinatal pathology.”
PLGA-Rhodamine from PolySciTech used in development of immunotherapy treatment of cancer
Monday, August 14, 2023, 4:11 PM ET
Macrophages are the bodies natural defense mechanism against disease and infection. These cells can be modified utilizing micropatches which attach to them and encourage them to attach cancer cells. Researchers at Harvard University utilized fluorescent PLGA-Rhodamine (AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of their development of macrophage cell engagers to target macrophages against cancer. This research holds promise to provide improved therapies against cancer in the future. Read more: Prakash, Supriya, Ninad Kumbhojkar, Andrew Lu, Neha Kapate, Vineeth Chandran Suja, Kyung Soo Park, Lily Li-Wen Wang, and Samir Mitragotri. "Polymer Micropatches as Natural Killer Cell Engagers for Tumor Therapy." ACS nano (2023). https://pubs.acs.org/doi/abs/10.1021/acsnano.3c03980
“Natural killer (NK) cell therapies have emerged as a potential therapeutic approach to various cancers. Their efficacy, however, is limited by their low persistence and anergy. Current approaches to sustain NK cell persistence in vivo include genetic modification, activation via pretreatment, or coadministration of supporting cytokines or antibodies. Such supporting therapies exhibit limited efficacy in vivo, in part due to the reversal of their effect within the immunosuppressive tumor microenvironment and off-target toxicity. Here, we report a material-based approach to address this challenge. Specifically, we describe the use of polymeric micropatches as a platform for sustained, targeted activation of NK cells, an approach referred to as microparticles as cell engagers (MACE). Poly(lactide-co-glycolic) acid (PLGA) micropatches, 4–8 μm in diameter and surface-modified with NK cell receptor targeting antibodies, exhibited strong adhesion to NK cells and induced their activation without the need of coadministered cytokines. The activation induced by MACE was greater than that induced by nanoparticles, attesting to the crucial role of MACE geometry in the activation of NK cells. MACE-bound NK cells remained viable and exhibited trans-endothelial migration and antitumor activity in vitro. MACE-bound NK cells activated T cells, macrophages, and dendritic cells in vitro. Adoptive transfer of NK-MACE also demonstrated superior antitumor efficacy in a mouse melanoma lung metastasis model compared to unmodified NK cells. Overall, MACE offers a simple, scalable, and effective way of activating NK cells and represents an attractive platform to improve the efficacy of NK cell therapy. KEYWORDS: NK cell NK engager NK cell activation cross-linking microparticle adoptive cell transfer lung metastasis”
Poly(N-isopropylacrylamide-co-methyl methacrylate) used in development of 3D bioprinting
Monday, August 7, 2023, 4:41 PM ET
A powerful analytical tool for testing of cancer therapeutics is constructing artificial tumors by 3D printing techniques in order to evaluate medicinal efficacy on them with accurate microenvironments. Researchers at Purdue University used PNIPAM-co-MMA (Cat# AO032) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to develop a bioink for 3D cell printing of tumor structures. This research holds promise to improve development of anticancer therapies in the future. Read more: Cheng, Cih, Naomi Deneke, Hye-ran Moon, Sae Rome Choi, Natalia Ospina-Muñoz, Bennett D. Elzey, Chelsea S. Davis, George T-C. Chiu, and Bumsoo Han. "Inkjet-printed morphogenesis of tumor-stroma interface using bi-cellular bioinks of collagen-poly (N-isopropyl acrylamide-co-methyl methacrylate) mixture." Materials Today Advances 19 (2023): 100408. https://www.sciencedirect.com/science/article/pii/S2590049823000681.
“Abstract: Recent advances in biomaterials and 3D printing/culture methods enable various tissue-engineered tumor models. However, it is still challenging to achieve native tumor-like characteristics due to lower cell density than native tissues and prolonged culture duration for maturation. Here, we report a new method to create tumoroids with a mechanically active tumor-stroma interface at extremely high cell density. This method, named “inkjet-printed morphogenesis” (iPM) of the tumor-stroma interface, is based on a hypothesis that cellular contractile force can significantly remodel the cell-laden polymer matrix to form densely-packed tissue-like constructs. Thus, differential cell-derived compaction of tumor cells and cancer-associated fibroblasts (CAFs) can be used to build a mechanically active tumor-stroma interface. In this methods, two kinds of bioinks are prepared, in which tumor cells and CAFs are suspended respectively in the mixture of collagen and poly (N-isopropyl acrylamide-co-methyl methacrylate) solution. These two cellular inks are inkjet-printed in multi-line or multi-layer patterns. As a result of cell-derived compaction, the resulting structure forms tumoroids with mechanically active tumor-stroma interface at extremely high cell density. We further test our working hypothesis that the morphogenesis can be controlled by manipulating the force balance between cellular contractile force and matrix stiffness. Furthermore, this new concept of “morphogenetic printing” is demonstrated to create more complex structures beyond current 3D bioprinting techniques.”
Corbion-Purasorb (R) Polymers now available from PolySciTech: Akina, Inc.
Monday, August 7, 2023, 1:43 PM ET
Streamline your development project with Purasorb® polymers now available as research products thanks to a distribution relationship between Corbion and Akina, Inc. (PolySciTech). Useful for long-acting injectables, medical devices, and other applications, these polymers provide a direct pathway towards clinical translation utilizing existing GMP manufactured products. Conveniently available with no minimum order and quick turn-around on purchase to meet your development needs.
https://akinainc.com/polyscitech/products/purasorb/
PLGA-Rhodamine from Akina, Inc. used in development of fluorescently traceable nanoparticles for biological interaction research
Monday, August 7, 2023, 1:42 PM ET
The way particles interact with cells and bodily systems greatly impacts their behavior for biomedical applications. Researchers at Université Paris-Saclay used PLGA-Rhodamine (cat# AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create fluorescent nanoparticles with a variety of sizes and shapes. They tested these for their cell interactions. This research holds promise to improve nanoformulations for drug-delivery applications in the future. Read more: Robin, Baptiste, Ludivine Mousnier, Hung Lê, Nadège Grabowski, David Chapron, Ophélie Bellance-Mina, Nicolas Huang, Florence Agnely, Elias Fattal, and Nicolas Tsapis. "PLA-PEG forming worm-like nanoparticles despite unfavorable packing parameter: formation mechanism, thermal stability and potential for cell internalization." International Journal of Pharmaceutics (2023): 123263. https://www.sciencedirect.com/science/article/pii/S037851732300683X
“Most nanoparticles produced for drug delivery purposes are spherical. However, the literature suggests that elongated particles are advantageous, notably in terms of cellular uptake. Thus, we synthesized biocompatible polylactide-b-poly(ethylene glycol) (PLA-PEG) polymers bearing carboxylate moieties, and used them to formulate worm-like nanoparticles by a simple emulsion-evaporation process. Worm-like nanoparticles with variable aspect ratio were obtained by simply adjusting the molar mass of the PLA block: the shorter the molar mass of the PLA block, the more elongated the particles. As PLA molar mass decreased from 80,000 g/mol to 13,000 g/mol, the proportion of worm-like nanoparticles increased from 0 to 46%, in contradiction with the usual behavior of block polymers based on their packing parameter. To explain this unusual phenomenon, we hypothesized the shape arises from a combination of steric and electrostatic repulsions between PEG chains bearing a carboxylate moiety present at the dichloromethane-water interface during the evaporation process. Worm-like particles turned out to be unstable when incubated at 37 °C, above polymer glass transition temperature. Indeed, above Tg, a Plateau-Rayleigh instability occurs, leading to the division of the worm-like particles into spheres. However, this instability was slow enough to assess worm-like particles uptake by murine macrophages. A slight but significant increase of internalization was observed for worm-like particles, compared to their spherical counterparts, confirming the interest of developing biocompatible anisotropic nanoparticles for pharmaceutical applications such as drug delivery.”
mPEG-PCL from PolySciTech used in development of methotrexate delivery system for treatment of ectopic pregnancy
Monday, August 7, 2023, 9:23 AM ET
Ectopic pregnancy is a potentially fatal condition in which an embryo develops outside the uterus. Researchers from Oregon Health & Science University, Oregon State University used mPEG-PCL (cat# AK001) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to deliver methotrexate as treatment for ectopic pregnancy. This research holds promise to provide for treatment of this potentially fatal situation. Read more: Mamnoon, Babak, Abraham S. Moses, Subisha Sundaram, Constanze J. Raitmayr, Terry Morgan, Maureen K. Baldwin, Leslie Myatt, Oleh Taratula, and Olena R. Taratula. "Glutathione‐Responsive Methotrexate Polymersomes for Potential Management of Ectopic Pregnancy." Small (2023): 2302969. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202302969
“The first-line treatment for ectopic pregnancy (EP), the chemotherapeutic methotrexate (MTX), has a failure rate of more than 10%, which can lead to severe complications or death. Inadequate accumulation of administered MTX at the ectopic implantation site significantly contributes to therapeutic failure. This study reports the first glutathione-responsive polymersomes for efficient delivery of MTX to the implantation site and its triggered release in placental cells. Fluorescence and photoacoustic imaging have confirmed that the developed polymersomes preferentially accumulate after systemic administration in the implantation site of pregnant mice at early gestational stages. The high concentrations of intracellular glutathione (GSH) reduce an incorporated disulfide bond within polymersomes upon internalization into placental cells, resulting in their disintegration and efficient drug release. Consequently, MTX delivered by polymersomes induces pregnancy demise in mice, as opposed to free MTX at the same dose regimen. To achieve the same therapeutic efficacy with free MTX, a sixfold increase in dosage is required. In addition, mice successfully conceive and birth healthy pups following a prior complete pregnancy demise induced by methotrexate polymersomes. Therefore, the developed MTX nanomedicine can potentially improve EP management and reduce associated mortality rates and related cost.”
PLGA-PEG-PLGA Thermogel From PolySciTech:Akina used in development of gemcitabine and rapamycin delivery system for pancreatic cancer therapy.
Monday, July 31, 2023, 3:48 PM ET
In 2021, pancreatic cancer was the 12th most common malignant tumor worldwide with a high mortality rate and poor prognosis. Researchers at Chungbuk National University, Huons Co., Sookmyung Women's University (Korea) used PLGA-PEG-PLGA (AK012 and AK019) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create thermogel solutions for delivery of synergistic gemcitabine and rapamycin drugs as a treatment for pancreatic cancer. This research holds promise to provide therapy against this deadly disease. Read more: Kim, Seo Yeon, Min Jeong Jo, Moon Sup Yoon, Chae Eun Jin, Yu Been Shin, Jae Min Lee, Hee Ji Shin et al. "Gemcitabine and rapamycin-loaded mixed polymeric thermogel for metastatic pancreatic cancer therapy." Journal of Controlled Release 360 (2023): 796-809. https://www.sciencedirect.com/science/article/pii/S0168365923004340
“Highlights: Gemcitabine and rapamycin show a synergistic effect at a molar ratio of 11:1. The 25% w/v mixed PLGA-PEG-PLGA thermogel (g(GR)) becomes a gel at 32 °C. The g(GR) has high encapsulation efficiency (>75%) and small size (<100 nm). The g(GR) most effectively suppressed Panc-1-luc2 tumor spheroid. The g(GR) showed no toxicity and suppressed tumors most effectively in mice. Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer–related death and has a poor 5–year overall survival. The superior therapeutic benefits of combination or co–administration of drugs as intraperitoneal chemotherapy have increased interest in developing strategies to deliver chemotherapeutic agents to patients safely. In this study, we prepared a gel comprising the thermosensitive poly(lactide–co–glycolide)–b–poly(ethylene glycol)–b–poly(lactide–co–glycolide) (PLGA–PEG–PLGA) polymer and gemcitabine (GEM), which is currently used as the primary chemotherapy for PDAC and rapamycin (RAPA), a mammalian TOR (mTOR) inhibitor, to deliver the drug through intraperitoneal injection. We performed in vitro cytotoxicity experiments to verify the synergistic effects of the two drugs at different molar ratios and characterized the physicochemical properties of the GEM, RAPA, and GEM/RAPA–loaded thermosensitive PLGA–PEG–PLGA gels, hereafter referred to as (g(G), g(R), and g(GR)), respectively. The g(GR) comprising PLGA–PEG–PLGA polymer (25% w/v) and GEM and RAPA at a molar ratio of 11:1 showed synergism and was optimized. An in vitro cytotoxicity assay was performed by treating Panc–1–luc2 tumor spheroids with g(G), g(R), or g(GR). The g(GR) treatment group showed a 2.75–fold higher inhibition rate than the non–treated (NT) and vehicle–treated groups. Furthermore, in vivo drug release assay in mice by intraperitoneal injection of g(G), g(R), or g(GR) showed a more rapid release rate of GEM than RAPA, similar to the in vitro release pattern. The drugs in the gel were released faster in vivo than in vitro and degraded in 48 h. In addition, g(GR) showed the highest anti–tumor efficacy with no toxicity to mice. These results provide evidence for the safety and efficacy of g(GR) for intraperitoneal drug delivery. This study will assist in developing and clinically administering topical anti–cancer formulations. Keywords: Combination therapy Pancreatic cancer therapy Intraperitoneal injection Gemcitabine Rapamycin Thermosensitive hydrogel”
Maleimide-PEG-PLGA from PolySciTech used in development of immunotherapy for diabetes treatment
Wednesday, July 12, 2023, 2:06 PM ET
Autoimmune Type 1 diabetes is a chronic condition that affects 1.25 million in USA, in which the pancreas produces little to no insulin due to immune system self-attack. The use of nanoparticles can be applied to shifting the immunologic balance and reducing immune attack. Researchers at Harvard University, Università di Milano, University of Florida, Qatar University, University of Sharjah, and University of Maryland used PEG-PLGA (AK102) and Mal-PEG-PLGA (AI110) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles decorated with targeting ligand MECA-79 and loaded with anti-CD3 therapeutic. This research holds promise to improve diabetes treatment. Read more: Jung, Sungwook, Moufida Ben Nasr, Baharak Bahmani, Vera Usuelli, Jing Zhao, Gianmarco Sabiu, Andy Joe Seelam et al. "Nano‐Targeted Delivery of Immune Therapeutics in type 1 Diabetes." Advanced Materials (2023): 2300812. https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.202300812
“Immune therapeutics hold great promise in the treatment of type 1 diabetes (T1D). Nonetheless, their progress has been hampered by limited efficacy, equipoise, or issues of safety. To address this, we developed a novel and specific nanodelivery platform for T1D that targets high endothelial venules (HEVs) presented in the pancreatic lymph nodes (PLNs) and pancreas. Our data indicate that the pancreata of non-obese diabetic (NOD) mice and patients with T1D are unique in their expression of newly formed HEVs. We encapsulated anti-CD3 mAb in PLGA-PEG nanoparticles (NPs), the surfaces of which were conjugated with MECA79 mAb that recognizes HEVs. Targeted delivery of these NPs improved accumulation of anti-CD3 mAb in both the PLNs and pancreata of NOD mice. Treatment of hyperglycemic NOD mice with MECA79-anti-CD3-NPs resulted in significant reversal of T1D compared to those that were untreated, treated with empty NPs, or provided free anti-CD3. This effect was associated with a significant reduction of T effector cell populations in the PLNs and a decreased production of pro-inflammatory cytokine in the mice treated with MECA79-anti-CD3-NPs. In sum, HEV-targeted therapeutics may be used as a means by which immune therapeutics can be delivered to PLNs and pancreata to suppress autoimmune diabetes effectively.”
Polylactide from PolySciTech used in development of composite scaffold for stroke treatment
Monday, July 3, 2023, 3:08 PM ET
Stroke occurs when blood vessel weakens and can even rupture often leading to severe morbidity or death. Use of grafting and stenosis techniques can repair vascular tissue to heal and prevent strokes. Researchers at Universitas Airlangga (Indonesia) used PLA (cat# AP006) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of scaffolding for vascular tissue repair. This research holds promise to provide improved therapy against stroke and other vascular diseases in the future. Read more: Suroto, Nur Setiawan, Asra Al Fauzi, Prihartini Widiyanti, and Fitria Renata Bella. "Biocompatibility Evaluation of Electrospun Poly-L Lactic acid-Chitosan Immobilized with Heparin as Scaffold for Vascular Tissue Repair." Journal of Science: Advanced Materials and Devices (2023): 100594. https://www.sciencedirect.com/science/article/pii/S2468217923000631
“Abstract: Stroke is the second leading cause of death worldwide, disability, high morbidity, and mortality. One of the leading causes of infarct stroke is carotid stenosis. The postoperative narrowing of the carotid artery diameter is a common complication after primary arterial closure in carotid endarterectomy surgery. A biomaterial design that combines synthetic and natural polymers is a promising strategy for patching arterial closure. In this paper, the electrospinning process was employed and Poly-L Lactic Acid (PLLA) was used as a base material. Chitosan and heparin were added to increase the biocompatibility of the biomaterial. The electrospun PLLA-chitosan immobilized with heparin (C sample) had better characteristics than the pure electrospun PLLA. The fiber diameter decreased to a micrometer scale and the pore size fell and became narrower, resulting in a smoother surface. Fiber diameter results for each sample were 1312.66 nm, 486.29 nm and 387.87 nm. Thereby potentially reducing the activation of blood coagulation and inflammation. The ultimate tensile strength test result for each sample were 2.28 MPa, 3.61 MPa and 3.25 MPa, for elongation results were 12.05%, 17.39%, and 18.14%, aligned with those of the human carotid artery and indicating potential use in patch angioplasty applications. This scaffold nanofiber was declared non-haemolytic for the C sample was 1.13% and non-cytotoxic. Percent viability for each sample was 89.35%, 83.81% and 78.92%. The in vivo host tissue response was shown to decrease pro-inflammatory cytokine expressions. This research shows that the proposed PLLA-chitosan-heparin biomaterial has strong physical properties and can modify the inflammatory response. However, it requires additional biofunctional alterations to optimize its tissue engineering capabilities.”
PLGA from PolySciTech used in research on bone-scaffold for tissue repair.
Monday, July 3, 2023, 3:07 PM ET
A powerful wound-healing technique is to implant a cell scaffold which provides a surface for the patient’s own cells to heal missing or damaged tissue. Researchers at Universitas Brawijaya (Indonesia) used PLGA (cat# AP082) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of development of a hydroxyapatite/PVA/PLGA bone scaffold. This research holds promise to provide for healing of bone lost due to disease or trauma. Read more: Istikharoh, Feni, Lalita El Milla, and Ericka Fairuz Ramadhani. "The Effect of the Addition of Poly Lactic co glycolic acid on the Porosity Of Nanoparticle Hydroxyapatite-Polyvinyl Alcohol Scaffold as Candidate Bonegraft Material." E-Prodenta Journal of Dentistry 7, no. 1 (2023): 717-724. https://eprodenta.ub.ac.id/index.php/eprodenta/article/view/202
“Background: Bone loss has a major impact on the process of placing implants and dentures. Nanoparticle hydroxyapatite (HANP) has better biodegradability and mechanical properties than micro-particle hydroxyapatite. PVA is a synthetic polymer that is cheap, hydrophilic, has high mechanical stability and flexibility but low biodegradability. PLGA is a new synthetic polymer which is widely used in the biomedical, however PLGA has less osteoconductive properties. The ideal scaffold has several important characteristics, one of which is having a porosity of>70%. Objective: To know the role of PLGA on the porosity of the scaffold by comparing the porosity of the HANP-PVA scaffold and the HANP-PVA scaffold given PLGA Methods: Group 1 was the HANP-PVA scaffold with a content of 20% HANP (w / w). Group 2 was the HANP-PVA scaffold which added 20% (w/w) of PLGA. Both groups were synthesized by freeze drying method at -80oC for 24 hours. The porosity test was used the liquid displacement method for 24 hours. Statistical testing using Shapiro Wilk, Levene's test and Independent t-Test Results: The porosity of the HANP-PVA scaffold was 77.90% ± 4.51 and the HANP-PVA-PLGA scaffold was 87.55% ± 5.67. The Shapiro-Wilk normality test showed that the data were normally distributed (p> 0.05). The independent t test showed a significant difference between the HANP-PVA and HANP-PVA-PLGA scaffold (p <0.05) Conclusions: The addition of PLGA to the scaffold can increase the porosity of the HANP-PVA scaffold. HANP-PVA-PLGA has the potential to accelerate bone regeneration after extraction. Keyword: bone loss, PVA, PLGA, Hydroxyapatite nanoparticle”
mPEG-PLGA from PolySciTech used in research on nanoparticle localization and drug delivery in cancerous tumors
Monday, July 3, 2023, 3:06 PM ET
Imaging and localization of fluorescent nanoparticles inside of living systems can provide incredible details regarding the internal structures and transport of particles within them. Given that ligands can be conjugated to the exterior surface of the nanoparticles, this provides for a powerful and robust technique to understand drug delivery in tissues. Researchers at University of Toronto used mPEG-PLGA (AK037) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of fluorescent nanoparticles for understanding drug transport inside of tumors. This research holds promise to provide for improved cancer therapy in the future. Read more: Syed, Abdullah Muhammad, Presley MacMillan, Jessica Ngai, Stefan Wilhelm, Shrey Sindhwani, Benjamin R. Kingston, Jamie LY Wu et al. "Liposome imaging in optically cleared tissues." Nano Letters 20, no. 2 (2020): 1362-1369. https://pubs.acs.org/doi/abs/10.1021/acs.nanolett.9b04853
“Three-dimensional (3D) optical microscopy can be used to understand and improve the delivery of nanomedicine. However, this approach cannot be performed for analyzing liposomes in tissues because the processing step to make tissues transparent for imaging typically removes the lipids. Here, we developed a tag, termed REMNANT, that enables 3D imaging of organic materials in biological tissues. We demonstrated the utility of this tag for the 3D mapping of liposomes in intact tissues. We also showed that the tag is able to monitor the release of entrapped therapeutic agents. We found that liposomes release their cargo >100-fold faster in tissues in vivo than in conventional in vitro assays. This allowed us to design a liposomal formulation with enhanced ability to kill tumor associated macrophages. Our development opens up new opportunities for studying the chemical properties and pharmacodynamics of administered organic materials in an intact biological environment. This approach provides insight into the in vivo behavior of degradable materials, where the newly discovered information can guide the engineering of the next generation of imaging and therapeutic agents. KEYWORDS: Nanoparticles CLARITY 3D imaging fluorescent label tissue clearing”
PEG-polyesters from PolySciTech used in development of automated nanoparticle synthesis
Friday, June 30, 2023, 4:36 PM ET
Nanoparticles can be utilized for a wide variety of drug delivery applications. However, their manufacturing must be carefully controlled to achieve good therapeutic results. Researchers at ETH Zürich (Switzerland) used PEG-PCL (AK128), PEG-PLA (AK056), and PEG-PLGA (AK037) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to make nanoparticles by automated process. This research holds promise to enable generation of highly controlled nanoparticles. Read more: Bovone, Giovanni, Fabian Steiner, Elia A. Guzzi, and Mark W. Tibbitt. "Automated and continuous production of polymeric nanoparticles." Frontiers in bioengineering and biotechnology 7 (2019): 423. https://www.frontiersin.org/articles/10.3389/fbioe.2019.00423/full
“Polymeric nanoparticles (NPs) are increasingly used as therapeutics, diagnostics, and building blocks in (bio)materials science. Current barriers to translation are limited control over NP physicochemical properties and robust scale-up of their production. Flow-based devices have emerged for controlled production of polymeric NPs, both for rapid formulation screening (~μg min−1) and on-scale production (~mg min−1). While flow-based devices have improved NP production compared to traditional batch processes, automated processes are desired for robust NP production at scale. Therefore, we engineered an automated coaxial jet mixer (CJM), which controlled the mixing of an organic stream containing block copolymer and an aqueous stream, for the continuous nanoprecipitation of polymeric NPs. The CJM was operated stably under computer control for up to 24 h and automated control over the flow conditions tuned poly(ethylene glycol)-block-polylactide (PEG5K-b-PLA20K) NP size between ≈56 nm and ≈79 nm. In addition, the automated CJM enabled production of NPs of similar size (Dh ≈ 50 nm) from chemically diverse block copolymers, PEG5K-b-PLA20K, PEG-block-poly(lactide-co-glycolide) (PEG5K-b-PLGA20K), and PEG-block-polycaprolactone (PEG5K-b-PCL20K), by tuning the flow conditions for each block copolymer. Further, the automated CJM was used to produce model nanotherapeutics in a reproducible manner without user intervention. Finally, NPs produced with the automated CJM were used to scale the formation of injectable polymer–nanoparticle (PNP) hydrogels, without modifying the mechanical properties of the PNP gel. In conclusion, the automated CJM enabled stable, tunable, and continuous production of polymeric NPs, which are needed for the scale-up and translation of this important class of biomaterials.”
PLGA-PEG-Maleimide from PolySciTech used in development of targeted nanotherapy against cancer
Monday, June 26, 2023, 3:09 PM ET
Tumor-specific peptides can be decorated on the outer surface of a nanoparticle formulation and utilized to target the particles towards cancer cells. Researchers at Queen's University Belfast, Cancer Research UK Manchester Institute, and Immunocore Ltd used PLGA-PEG-Mal (Cat# AI020) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create T-cell receptor targeted nanoparticles to deliver docetaxel to tumors. This research holds promise to provide for treatment against cancer. Read More: McDaid, William J., Nikolai Lissin, Ellen Pollheimer, Michelle Greene, Adam Leach, Peter Smyth, Giovanna Bossi, Daniel Longley, David K. Cole, and Christopher J. Scott. "Enhanced target-specific delivery of docetaxel-loaded nanoparticles using engineered T cell receptors." Nanoscale 13, no. 35 (2021): 15010-15020. https://pubs.rsc.org/en/content/articlehtml/2021/nr/d1nr04001d
“For effective targeted therapy of cancer with chemotherapy-loaded nanoparticles (NPs), antigens that are selective for cancer cells should be targeted to minimise off-tumour toxicity. Human leukocyte antigens (HLAs) are attractive cancer targets as they can present peptides from tumour-selective proteins on the cell surface, which can be recognised by T cells via T cell receptors (TCRs). In this study, docetaxel-loaded polymeric NPs were conjugated to recombinant affinity-enhanced TCRs to target breast cancer cells presenting a tumour-selective peptide-HLA complex. The TCR-conjugated nanoparticles enabled enhanced delivery of docetaxel and induced cell death through tumour-specific peptide-HLA targeting. These in vitro data demonstrate the potential of targeting tumour-restricted peptide-HLA epitopes using high affinity TCR-conjugated nanoparticles, representing a novel treatment strategy to deliver therapeutic drugs specifically to cancer cells.”
mPEG-PLGA from PolySciTech used in development of nanoparticles for immunotherapy against cancer
Wednesday, June 14, 2023, 11:44 AM ET
Cancer has several mechanisms which allow it to evade the human immune system. Overcoming these attributes and triggering the immune system to attack the cancer cells directly is the goal of immunotherapy. Researchers at Chinese Academy of Sciences (Beijing) used PEG-PLGA (Cat# AK010) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create multi-functional nanoparticles which reduce cancers ability to evade the immune system. This research holds promise to improve therapy against cancer in the future. Read more: Li, L., Zhen, M., Wang, H., Sun, Z., Cao, X., Li, J., Liu, S., Zhao, Z., Zhou, C., Wang, C. and Bai, C., 2023. Tumor microenvironment-modulated multiple nanotherapeutic system for potent cancer immunotherapy and metastasis inhibition. Nano Today, 48, p.101702. https://www.sciencedirect.com/science/article/pii/S1748013222003309
“Abstract: The hypoxic and immunosuppressive tumor microenvironment (TME) generally weaken the efficacy of immunotherapy in solid tumors. However, reversing TME remains a formidable challenge. Here, an elaborately multitasking nanotherapeutic system (PEG-PLGA-R848@GFCNs) is demonstrated to forceful remodel TME. This nanotherapeutic system could validly relieve tumor hypoxia and induce M2 to M1 polarization of tumor-associated macrophages (TAMs) to reverse immunosuppression, serving for TME reprogramming. Furthermore, PEG-PLGA-R848@GFCNs stimulates dendritic cells maturation, thereby initiating T-cell-mediated anti-tumor immune response. Of note, the nanotherapeutic system eliminates primary tumor that established by 4T1 tumor models in mice and efficiently inhibits B16F10 melanoma metastasis without obvious adverse effects. Importantly, PEG-PLGA-R848@GFCNs combined with anti-PD-L1 immune checkpoint inhibitor achieves superior synergistic cancer immunotherapy. Collectively, our work offers a reliable and safe strategy to fabricate a multitasking nanotherapeutic system for comprehensively modulating TME to achieve effective cancer immunotherapy and metastasis inhibition.”
Video: https://youtu.be/tF-V4wB8ZwY
Polylactide from PolySciTech used in development of bone-tissue repair scaffold.
Friday, June 9, 2023, 2:52 PM ET
Bone tissue can be damaged by disease or injury however the body may not be able to readily regrow damaged or missing bone. Growth can be improved by providing a scaffold which mimics the extracellular matrix and helps cells regrow bone tissue. Researchers from University of Salerno (Italy) and Universidade de Santiago de Compostela (Spain) used PLA (Cat# AP231) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a bioactive mesh for bone repair. This research holds promise to provide for repair of bone tissue. Read more: Tommasino, Carmela, Giulia Auriemma, Carla Sardo, Carmen Alvarez-Lorenzo, Emilia Garofalo, Silvana Morello, Giovanni Falcone, and Rita P. Aquino. "3D printed macroporous scaffolds of PCL and inulin-gP (D, L) LA for bone tissue engineering applications." International Journal of Pharmaceutics (2023): 123093. https://www.sciencedirect.com/science/article/pii/S0378517323005136
“Abstract: Bone repair and tissue-engineering (BTE) approaches require novel biomaterials to produce scaffolds with required structural and biological characteristics and enhanced performances with respect to those currently available. In this study, PCL/INU-PLA hybrid biomaterial was prepared by blending of the aliphatic polyester poly(ε-caprolactone) (PCL) with the amphiphilic graft copolymer Inulin-g-poly(D,L)lactide (INU-PLA) synthetized from biodegradable inulin (INU) and poly(lactic acid) (PLA). The hybrid material was suitable to be processed using fused filament fabrication 3D printing (FFF-3DP) technique rendering macroporous scaffolds. PCL and INU-PLA were firstly blended as thin films through solvent-casting method, and then extruded by hot melt extrusion (HME) in form of filaments processable by FFF-3DP. The physicochemical characterization of the hybrid new material showed high homogeneity, improved surface wettability/hydrophilicity as compared to PCL alone, and right thermal properties for FFF process. The 3D printed scaffolds exhibited dimensional and structural parameters very close to those of the digital model, and mechanical performances compatible with the human trabecular bone. In addition, in comparison to PCL, hybrid scaffolds showed an enhancement of surface properties, swelling ability, and in vitro biodegradation rate. In vitro biocompatibility screening through hemolysis assay, LDH cytotoxicity test on human fibroblasts, CCK-8 cell viability, and osteogenic activity (ALP evaluation) assays on human mesenchymal stem cells showed favorable results.”
Video: https://youtu.be/GVGEDbjIfhE
PLGA from PolySciTech used in development of computational modeling for drug-delivery formulations
Tuesday, June 6, 2023, 3:50 PM ET
Diffusion of drugs through biodegradable polymer systems relies on several properties of the drug, polymer, and formulation parameters. These various properties can be utilized along with computational modeling to calculate the drug-release behaviors. Researchers at Purdue University used PLGA (Cat# AP041) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to investigate the impact of formulation parameters on biodegradable drug-release systems and compare these to computationally predicted results. This research holds promise to improve formulation approaches in the future. Read more: Giolando, Patrick A., Kelsey Hopkins, Barrett Davis, Nicole Vike, Adib Ahmadzadegan, Arezoo Ardekani, Pavlos Vlachos, Joseph Rispoli, Luis Solorio, and Tamara L. Kinzer‐Ursem. "Mechanistic computational modeling of implantable, bioresorbable, drug release systems." Advanced Materials (2023): 2301698. https://onlinelibrary.wiley.com/doi/abs/10.1002/adma.202301698
“Implantable, bioresorbable drug delivery systems offer an alternative to current drug administration techniques; allowing for patient-tailored drug dosage, while also increasing patient compliance. Mechanistic mathematical modeling allows for the acceleration of the design of the release systems, and for prediction of physical anomalies that are not intuitive and might otherwise elude discovery. This study investigates short-term drug release as a function of water-mediated polymer phase inversion into a solid depot within hours to days, as well as long-term hydrolysis-mediated degradation and erosion of the implant over the next few weeks. Finite difference methods were used to model spatial and temporal changes in polymer phase inversion, solidification, and hydrolysis. Modeling revealed the impact of non-uniform drug distribution, production and transport of H+ ions, and localized polymer degradation on the diffusion of water, drug, and hydrolyzed polymer byproducts. Compared to experimental data, the computational model accurately predicted the drug release during the solidification of implants over days and drug release profiles over weeks from microspheres and implants. This work offers new insight into the impact of various parameters on drug release profiles, and is a new tool to accelerate the design process for release systems to meet a patient specific clinical need.”
Video: https://youtu.be/WfCgdxeaFu8
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/
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