PCL from PolySciTech used in development of nano-polyhedron drug delivery platform.

 

Combinations of metal compounds with polymers can enable unique drug-delivery options. Researchers at China Three Gorges University used PCL (AP257) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create mixed nanoparticles containing selenium and Riboflavin as a model drug delivery system. This research holds promise to provide for a wide array of targeted delivery applications. Read more: Zhu, Lixian, Yanhua Wang, Luping Rao, and Xin Yu. "Se-incorporated polycaprolactone spherical polyhedron enhanced vitamin B2 loading and prolonged release for potential application in proliferative skin disorders." Colloids and Surfaces B: Biointerfaces 245 (2025): 114295. https://www.sciencedirect.com/science/article/pii/S092777652400554X

“Highlights: The introduction of Se into PCL@VitB2 spherical polyhedrons reduces their particle size and crystallinity. Se-PCL spherical polyhedrons perform higher loading efficiency for Vitamin B2 than pure PCL spherical polyhedrons. Se-PCL@VitB2 spherical polyhedrons exhibit slowly prolonged Vitamin B2 release in physical buffers. Se-PCL@VitB2 spherical polyhedrons present strong inhibitory effect on the growth of epidermal HaCat cells, but are compatible to BMSC cells. Abstract: Development of novel drug vehicles for vitamin B2 (VitB2) delivery is very important for designing controllable release system to improve epidermal growth and bone metabolism. In this work, selenium (Se)-incorporated polycaprolactone (PCL) spherical polyhedrons are successfully synthesized via a single emulsion solvent evaporation method which is utilized to load VitB2 to fabricate cell-responsive Se-PCL@VitB2 delivery systems. Their physicochemical properties are characterized by DLS, SEM, XRD, FTIR, and TGA-DSC. The release kinetics of VitB2 or Se from the samples are investigated in PBS solution (pH = 2.0, 5.0, 7.4, 8.0 and 12.0). The cytocompatibilities are also evaluated with normal BMSC and epidermal HaCat cells. Results exhibit that Se-PCL@VitB2 particles presents spherical polyhedral morphology (approximately (3.25 ± 0.46) μm), negative surface charge (-(54.03 ± 2.94) mV), reduced crystallinity and good degradability. Stability experiments imply that both VitB2 and Se might be uniformly dispersed in PCL matrix. And the incorporation of Se facilely promotes the loading of VitB2. The encapsulation efficiency and loading capacity are (98.42 ± 1.06)% and (76.25 ± 1.27) for Se-PCL@VitB2 sample. Importantly, it exhibits more prolonged release of both VitB2 and Se in neutral PBS solution (pH = 7.4) than other pH conditions. Presumably, the electrostatic interaction between Se, VitB2 and PCL contribute to its release mode. Cell experiments show that Se-PCL@VitB2 presents strong cytotoxicity to HaCat cells mainly due to the cytotoxic effect of Se anions and PCL degradation products. However, it exhibits weak inhibitory effect on BMSC cells. These note that the synthesized Se-PCL@VitB2 particles can be promising drug vehicles for potential application in epidermal proliferative disorders.”

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PLGA-PEG-Maleimide and PEG-PLGA used in development of nanoparticles for oral delivery of semaglutide

 

GLP1 agonists are widely used in treatment of diabetes and other disease states. These drugs have poor oral bioavailability. Researchers at Universidade do Porto, Novo Nordisk, KTH Royal Institute of Technology, Roslagstullsbacken, University of Groningen used PLGA-PEG-Mal (AI110) and mPEG-PLGA (AK106) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles to pass through the intestine to provide for oral delivery of semaglutide. This research holds promise to provide for improved treatment of diabetes. Read more: Pinto, Soraia, Juliana Viegas, Cecília Cristelo, Catarina Pacheco, Sofia Barros, Stephen T. Buckley, Javad Garousi, Torbjörn Gräslund, Hélder A. Santos, and Bruno Sarmento. "Bioengineered Nanomedicines Targeting the Intestinal Fc Receptor Achieve the Improved Glucoregulatory Effect of Semaglutide in a Type 2 Diabetic Mice Model." ACS nano (2024). https://pubs.acs.org/doi/abs/10.1021/acsnano.4c11172

“The oral administration of the glucagon-like peptide-1 analogue, semaglutide, remains a hurdle due to its limited bioavailability. Herein, neonatal Fc receptor (FcRn)-targeted nanoparticles (NPs) were designed to enhance the oral delivery of semaglutide. The nanocarriers were covalently linked to the FcRn-binding peptide FcBP or the affibody molecule ZFcRn that specifically binds to the human FcRn (hFcRn) in a pH-dependent manner. These FcRn-targeted ligands were selected over the endogenous ligands of the receptor (albumin and IgG) due to their smaller size and simpler structure, which could facilitate the transport of functionalized NPs through the tissues. The capacity of FcRn-targeted semaglutide-NPs in controlling the blood glucose levels was evaluated in an hFcRn transgenic mice model, where type 2 diabetes mellitus (T2DM) was induced via intraperitoneal injection of nicotinamide followed by streptozotocin. The encapsulation of semaglutide into FcRn-targeted NPs was translated in an improved glucoregulatory effect in T2DM-induced mice when compared to the oral free semaglutide or nontargeted NP groups, after daily oral administrations for 7 days. Notably, a similar glucose-lowering response was observed between both FcRn-targeted NPs and the subcutaneous semaglutide groups. An increase in insulin pancreatic content and a recovery in β cell mass were visualized in the mice treated with FcRn-targeted semaglutide-NPs. The biodistribution of fluorescently labeled NPs through the gastrointestinal tract demonstrated that the nanosystems targeting the hFcRn are retained longer in the ileum and colorectum, where the expression of FcRn is more prevalent, than nontargeted NPs. Therefore, FcRn-targeted nanocarriers proved to be an effective platform for improving the pharmacological effect of semaglutide in a T2DM-induced mice model.”

PEG-PLGA (Cat# AK106): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK106#h

PLGA-PEG-Mal (Cat# AI110): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI110#h

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PLGA-PEG-amine from PolySciTech used in development of nanoparticles for brain-tissue penetration

 

Delivery of medicinal molecules into the brain is difficult due to the blood-brain-barrier. Researchers at University of Technology Sydney and The University of Adelaide used PLGA-PEG-NH2 (AI058) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles enveloped in a protein corona. They used these particles to investigate mechanisms of uptake and delivery in brain tissue. This research holds promise to provide for improved therapies against brain diseases such as cancer and Alzheimer’s. Read more: Morshed, Nabila, Claire Rennie, Wei Deng, Lyndsey Collins-Praino, and Andrew Care. "Serum-derived protein coronas affect nanoparticle interactions with brain cells." Nanotechnology 35, no. 49 (2024): 495101. https://new.iopscience.iop.org/article/10.1088/1361-6528/ad7b40

“Neuronanomedicine is an emerging field bridging the gap between neuromedicine and novel nanotherapeutics. Despite promise, clinical translation of neuronanomedicine remains elusive, possibly due to a dearth of information regarding the effect of the protein corona on these neuronanomedicines. The protein corona, a layer of proteins adsorbed to nanoparticles following exposure to biological fluids, ultimately determines the fate of nanoparticles in biological systems, dictating nanoparticle–cell interactions. To date, few studies have investigated the effect of the protein corona on interactions with brain-derived cells, an important consideration for the development of neuronanomedicines. Here, two polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and PLGA-polyethylene glycol (PLGA-PEG), were used to obtain serum-derived protein coronas. Protein corona characterization and liquid chromatography mass spectrometry analysis revealed distinct differences in biophysical properties and protein composition. PLGA protein coronas contained high abundance of globins (60%) and apolipoproteins (21%), while PLGA-PEG protein coronas contained fewer globins (42%) and high abundance of protease inhibitors (28%). Corona coated PLGA nanoparticles were readily internalized into microglia and neuronal cells, but not into astrocytes. Internalization of nanoparticles was associated with pro-inflammatory cytokine release and decreased neuronal cell viability, however, viability was rescued in cells treated with corona coated nanoparticles. These results showcase the importance of the protein corona in mediating nanoparticle–cell interactions.”

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PLGA from PolySciTech used in development of nanoparticles for treatment of atherosclerosis

 

Atherosclerosis (heart-disease) is due to formation of lipid-laden plaques in the arteries. These plaques typically express immunosuppressive signals which prevents their removal by immune system. Recently, researchers at University of Ottawa utilized PLGA (AP023) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles to deliver immunotargeting compounds to plaques. This research holds promise as a potential treatment for heart disease. Read more: Patel, Yukta, Shireesha Manturthi, Saras Tiwari, Esha Gahunia, Amandine Courtemanche, Michelle Gandelman, Marceline Côté, and Suresh Gadde. "Development of Pro-resolving and Pro-efferocytic Nanoparticles for Atherosclerosis Therapy." ACS Pharmacology & Translational Science (2024). https://pubs.acs.org/doi/abs/10.1021/acsptsci.4c00292

“Atherosclerosis is a major contributor to cardiovascular diseases with a high global prevalence. It is characterized by the formation of lipid-laden plaques in the arteries, which eventually lead to plaque rupture and thrombosis. While the current lipid-lowering therapies are generally effective in lowering the risk of cardiovascular events, they do not address the underlying causes of disease. Defective resolution of inflammation and impaired efferocytosis are the main driving forces of atherosclerosis. Macrophages recognize cells for clearance by the expression of “eat me” and “do not eat me” signals, including the CD47-SIRPα axis. However, the “do not eat me” signal CD47 is overexpressed in atherosclerotic plaques, leading to compromised efferocytosis and secondary necrosis. In this context, prophagocytic antibodies have been explored to stimulate the clearance of apoptotic cells, but they are nonspecific and impact healthy tissues. In macrophages, downstream of signal regulatory protein α, lie protein tyrosine phosphatases, SHP 1/2, which can serve as effective targets for selectively phagocytosing apoptotic cells. While increasing the efferocytosis targets the end stages of lesion development, the underlying issue of inflammation still persists. Simultaneously increasing efferocytosis and reducing inflammation can be effective therapeutic strategies for managing atherosclerosis. For instance, IL-10 is a key anti-inflammatory mediator that enhances efferocytosis via phosphoSTAT3 (pSTAT3) activation. In this study, we developed a combination nanotherapy by encapsulating an SHP-1 inhibitor (NSC 87877) and IL-10 in a single nanoparticle platform [(S + IL)-NPs] to enhance efferocytosis and inflammation resolution. Our studies suggest that (S + IL)-NPs successfully encapsulated both agents, entered the macrophages, and delivered the agents into intracellular compartments. Additionally, (S + IL)-NPs decreased inflammation by suppressing pro-inflammatory markers and enhancing anti-inflammatory mediators. They also exhibited the potential for improved phagocytic activity via pSTAT3 activation. Our nanomedicine-mediated upregulation of the anti-inflammatory and efferocytic responses in macrophages shows promise for the treatment of atherosclerosis.”

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PLGA-PEG-Mal from PolySciTech used in development of nano-delivery system for glioblastoma treatment

 

Glioblastoma is an aggressive brain cancer that is difficult to treat. Researchers at Southern University of Science and Technology, University of Texas Southwestern Medical Center, Xuzhou Medical University used PLGA-PEG-Maleimide (AI110) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles for targeting glioblastoma. They utilized this as part of a multifunctional system to maximize both radiotherapy and also immunotherapy against glioblastoma. Read more: Wen, Xin, Zhiying Shao, Xueting Chen, Hongmei Liu, Hui Qiu, Xin Ding, Debao Qu, Hui Wang, Andrew Z. Wang, and Longzhen Zhang. "A multifunctional targeted nano-delivery system with radiosensitization and immune activation in glioblastoma." Radiation Oncology 19, no. 1 (2024): 1-20. https://ro-journal.biomedcentral.com/articles/10.1186/s13014-024-02511-9

“Glioblastoma (GBM), the most common primary brain malignancy in adults, is notoriously difficult to treat due to several factors: tendency to be radiation resistant, the presence of the blood brain barrier (BBB) which limits drug delivery and immune-privileged status which hampers effective immune responses. Traditionally, high-dose irradiation (8 Gy) is known to effectively enhance anti-tumor immune responses, but its application is limited by the risk of severe brain damage. Currently, conventional dose segmentation (2 Gy) is the standard radiotherapy method, which does not fully exploit the potential of high-dose irradiation for immune activation. The hypothesis of our study posits that instead of directly applying high doses of radiation, which is risky, a strategy could be developed to harness the immune-stimulating benefits of high-dose irradiation indirectly. This involves using nanoparticles to enhance antigen presentation and immune responses in a safer manner. Angiopep-2 (A2) was proved a satisfactory BBB and brain targeting and Dbait is a small molecule that hijack DNA double strand break damage (DSB) repair proteins to make cancer cells more sensitive to radiation. In view of that, the following two nanoparticles were designed to combine immunity of GBM, radiation resistance and BBB innovatively. One is cationic liposome nanoparticle interacting with Dbait (A2-CL/Dbait NPs) for radiosensitization effect; the other is PLGA-PEG-Mal nanoparticle conjugated with OX40 antibody (A2-PLGA-PEG-Mal/anti-OX40 NPs) for tumor-derived protein antigens capture and optimistic immunoregulatory effect of anti-OX40 (which is known to enhance the activation and proliferation T cells). Both types of nanoparticles showed favorable targeting and low toxicity in experimental models. Specifically, the combination of A2-CL/Dbait NPs and A2-PLGA-PEG-Mal/anti-OX40 NPs led to a significant extension in the survival time and a significant tumor shrinkage of mice with GBM. The study demonstrates that combining these innovative nanoparticles with conventional radiotherapy can effectively address key challenges in GBM treatment. It represents a significant step toward more effective and safer therapeutic options for GBM patients.”

PLGA-PEG-Mal (Cat# AI110): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI110#h

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PLGA-PEG-PLGA Thermogels from PolySciTech used in development of controlled antibody release system

 

Thermogels have the ability to dissolve in cold water and form solid, gel structures when heated to body temperature. This allows them to deliver delicate molecules, like antibodies, which typically break down under normal processing conditions to form microparticles. Researchers at the Polish Academy of Sciences used PLGA-PEG-PLGA (AK012, AK024, AK088, AK091) and PLCL-PEG-PLCL (AK108) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a gel to deliver antibodies. This research holds promise to provide for improved biotherapy techniques in the future. Read more: Lipowska-Kur, Daria, Łukasz Otulakowski, Urszula Szeluga, Katarzyna Jelonek, and Alicja Utrata-Wesołek. "Diverse Strategies to Develop Poly (ethylene glycol)–Polyester Thermogels for Modulating the Release of Antibodies." Materials 17, no. 18 (2024): 4472. https://www.mdpi.com/1996-1944/17/18/4472

“Abstract: In this work, we present basic research on developing thermogel carriers containing high amounts of model antibody immunoglobulin G (IgG) with potential use as injectable molecules. The quantities of IgG loaded into the gel were varied to evaluate the possibility of tuning the dose release. The gel materials were based on blends of thermoresponsive and degradable ABA-type block copolymers composed of poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA–PEG–PLGA) or poly(lactide-co-caprolactone)-b-poly(ethylene glycol)-b-(lactide-co-caprolactone) (PLCL–PEG–PLCL). Primarily, the gels with various amounts of IgG were obtained via thermogelation, where the only factor inducing gel formation was the change in temperature. Next, to control the gels’ mechanical properties, degradation rate, and the extent of antibody release, we have tested two approaches. The first one involved the synergistic physical and chemical crosslinking of the copolymers. To achieve this, the hydroxyl groups located at the ends of the PLGA–PEG–PLGA chain were modified into acrylate groups. In this case, the thermogelation was accompanied by chemical crosslinking through the Michael addition reaction. Such an approach increased the dynamic mechanical properties of the gels and simultaneously prolonged their decomposition time. An alternative solution was to suspend crosslinked PEG–polyester nanoparticles loaded with IgG in a PLGA–PEG–PLGA gelling copolymer. We observed that loading IgG into thermogels lowered the gelation temperature (TGEL) value and increased the storage modulus of the gels, as compared with gels without IgG. The prepared gel materials were able to release the IgG from 8 up to 80 days, depending on the gel formulation and on the amount of loaded IgG. The results revealed that additional, chemical crosslinking of the thermogels and also suspension of particles in the polymer matrix substantially extended the duration of IgG release. With proper matching of the gel composition, environmental conditions, and the type and amount of active substances, antibody-containing thermogels can serve as effective IgG delivery materials. Keywords: thermogels; sol-gel transition; tandem gelation; polymer degradation; nanoparticles; antibody”

PLCL-PEG-PLCL (Cat# AK108): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK108#h

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