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-PLGA from PolySciTech used in development of ocular release platform for treatment of secondary cataracts
Thursday, June 27, 2024, 11:47 AM ET
Cataracts are the second leading cause of blindness with over 100 million cataract surgeries performed worldwide. A common complication from cataract surgery is the formation of ‘secondary cataracts’ created by tissue response to the surgical process. Researchers at Rowan University, Philadelphia College of Osteopathic Medicine, Genisphere, LLC, and OcuMedic, Inc., used thermogelling PLGA-PEG-PLGA (cat# AK097) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a gel formulation for the controlled release of therapeutic DNA which reduces secondary cataract formation. This research holds promise to provide for treatment against cataract-induced blindness. Read more: Vardar, Camila, Mindy George-Weinstein, Robert Getts, and Mark E. Byrne. "Evaluation of Dose–Response Relationship in Novel Extended Release of Targeted Nucleic Acid Nanocarriers to Treat Secondary Cataracts." Journal of Ocular Pharmacology and Therapeutics (2024). https://www.liebertpub.com/doi/abs/10.1089/jop.2024.0024
“Abstract: Purpose: The present study aimed to determine the dose–response relationship between targeted nanocarriers released from a novel, sustained release formulation and their ability to specifically deplete cells responsible for the development of posterior capsular opacification (PCO) in month-long, dynamic cell cultures. Methods: Injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) triblock copolymer hydrogels were loaded with either a low or a high dose of doxorubicin-loaded antibody-targeted nanocarriers (G8:3DNA:Dox). Human rhabdomyosarcoma cells, selected for their expression of PCO marker brain-specific angiogenesis inhibitor 1 (BAI1), were kept under dynamic media flow and received either a low or high dose of nanocarriers. Cells were fixed and stained at predetermined time points to evaluate targeted depletion of BAI1+ cells. Results: A lower dose of nanocarriers in hydrogel depleted BAI1+ cells at a slower rate than the higher dose, whereas both reached over 90% BAI1+ cellular nonviability at 28 days. Both treatment groups also significantly lowered the relative abundance of BAI1+ cells in the population compared with the control group. Conclusions: Controlled release of a lower dose of nanocarriers can still achieve therapeutically relevant effects in the prevention of PCO, while avoiding potential secondary effects associated with the administration of a higher dose.”
PLGA-PEG-PLGA AK097: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK097#h
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PLGA from PolySciTech used in development of anti-viral delivery system for treatment of respiratory diseases
Wednesday, June 26, 2024, 4:47 PM ET
The pandemic highlighted the need to provide for reliable treatment of respiratory diseases. One way to treat a viral respiratory disease is to deliver a high dose of antiviral agent in a localized manner to the respiratory tissue. This is optimally achieved with an inhaled formulation which can deliver drugs to the affect lung and throat tissues quickly. Researchers at University of Texas at Arlington and University of Southern Mississippi used PLGA (catalog # AP040) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a nanoparticle drug delivery system for inhaled delivery of antiviral Remdesivir. This antiviral agent can be used as a therapeutic option for respiratory diseases in the future. Read more: Chintapula, Uday, Shazeed-Ul Karim, Priyanka Raghunathan Iyer, Haritha Asokan-Sheeja, Biswas Neupane, Farzana Nazneen, He Dong, Fengwei Bai, and Kytai T. Nguyen. "A novel nanocomposite drug delivery system for SARS-CoV-2 infections." (2024). https://www.researchgate.net/profile/Farzana-Nazneen-2/publication/381502779_A_novel_nanocomposite_drug_delivery_system_for_SARS-CoV-2_infections/links/6671dd25b769e7691940c595/A-novel-nanocomposite-drug-delivery-system-for-SARS-CoV-2-infections.pdf
“To develop an inhalable drug delivery system, we synthesized poly (lactic-co-glycolic acid) nanoparticles with Remdesivir (RDV NPs) as an antiviral agent against SARS-CoV-2 replication and formulated Remdesivir-loaded nanocomposites (RDV NCs) via coating of RDV NPs with novel supramolecular cellpenetrating peptide nanofibers (NFs) to enhance cellular uptake and intracellular drug delivery. RDV NPs and RDV NCs were characterized using variou techniques, including Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and fluorescent microscopy. The cytotoxicity of RDV NCs was assessed in Vero E6 cells and primary human lung epithelial cells, with no significant cytotoxicity observed up to 1000 mgmL−1 and 48 h. RDV NCs were spherically shaped with a size range of 200300 nm and a zeta potential of ∼+31 mV as well as indicating the presence of coated nanofibers. Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR), immunofluorescence and plaque assays of SARS-CoV-2 infected Vero E6 treated with RDV NCs showed significantly higher antiviral activities compared to those of free drug and uncoated RDV NPs. RDV NCs exhibited high antiviral activity against SARS-CoV-2, and the nanocomposite platform has the potential to be developed into an inhalable drug delivery system for other viral infections in the lungs.”
PLGA AP040: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AP040#h
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PLGA-PEG-NH2 from PolySciTech used in development of cerebrospinal-protein corona-covered nanoparticles to study neural cell interactions
Wednesday, June 19, 2024, 9:33 AM ET
Treatment of diseases within the brain, ranging from glioblastoma to Alzheimer's, remains difficult in part due to the blood-brain-barrier. The details of the interactions between proteins and neural cells remain poorly understood which inhibits development of therapies to deliver medicinal molecules into the brain. Researchers at the University of Technology Sydney, The University of Melbourne, and The University of Adelaide used PLGA-PEG-NH2 (cat# AI169) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles covered with cerebrospinal proteins. They used these to research the interactions of such particles with neural cells. This research holds promise to improve drug delivery to brain tissue for treatment of a variety of disease states. Read more: Morshed, Nabila, Claire Rennie, Matthew Faria, Lyndsey E. Collins-Praino, and Andrew Care. "Protein Coronas Derived from Cerebrospinal Fluid Enhance the Interactions Between Nanoparticles and Brain Cells." bioRxiv (2024): 2024-05. https://www.biorxiv.org/content/10.1101/2024.05.31.596763.abstract
“Neuronanomedicine harnesses nanoparticle technology for the treatment of neurological disorders. An unavoidable consequence of nanoparticle delivery to biological systems is the formation of a protein corona on the nanoparticle surface. Despite the well-established influence of the protein corona on nanoparticle behavior and fate, as well as FDA approval of neuro-targeted nanotherapeutics, the effect of a physiologically relevant protein corona on nanoparticle-brain cell interactions is insufficiently explored. Indeed, less than 1% of protein corona studies have investigated protein coronas formed in cerebrospinal fluid (CSF), the fluid surrounding the brain. Herein, we utilize two clinically relevant polymeric nanoparticles (PLGA and PLGA-PEG) to evaluate the formation of serum and CSF protein coronas. LC-MS analysis revealed distinct protein compositions, with selective enrichment/depletion profiles. Following incubation with brain cells, serum and CSF coronas on PLGA particles showed enhanced associations with all cell types as compared to their corresponding corona on PLGA-PEG particles. CSFderived protein coronas on PLGA nanoparticles, specifically, showed the greatest nanoparticle-cell interactions, with Pearson’s correlation analysis revealing that proteins associated with enhanced nanoparticle-cell interactions were exclusively enriched in this protein corona. This study demonstrates the importance of correct choice of physiologically relevant biological fluids, and its influence on the formation of the protein corona, subsequent nanoparticle-cell interactions. Keywords: protein corona; bio-nano interactions, neuronanomedicine; cerebrospinal fluid; neurons; glia; targeted drug delivery”
AI169: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI169#h
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mPEG-PLGA from PolySciTech used in development of polymeric nanoparticles combination therapy.
Friday, June 14, 2024, 5:01 PM ET
Cancer typically requires multiple drug therapies for its treatment however delivery of medicinal molecules is difficult. Researchers at University of Adelaide utilized mPEG-PLGAs (Cat# AK010 and AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop multi-drug delivery nanoparticles for cancer therapy applications. This research holds promise to provide for improved therapy against cancer in the future. Read more: Jin, Song, Zhenwei Lan, Guangze Yang, Xinyu Li, Javen Qinfeng Shi, Yun Liu, and Chun‐Xia Zhao. "Computationally guided design and synthesis of dual‐drug loaded polymeric nanoparticles for combination therapy." Aggregate (2024): e606. https://onlinelibrary.wiley.com/doi/abs/10.1002/agt2.606
“Single-drug therapies or monotherapies are often inadequate, particularly in the case of life-threatening diseases like cancer. Consequently, combination therapies emerge as an attractive strategy. Cancer nanomedicines have many benefits in addressing the challenges faced by small molecule therapeutic drugs, such as low water solubility and bioavailability, high toxicity, etc. However, it remains a significant challenge in encapsulating two drugs in a nanoparticle. To address this issue, computational methodologies are employed to guide the rational design and synthesis of dual-drug-loaded polymer nanoparticles while achieving precise control over drug loading. Based on the sequential nanoprecipitation technology, five factors are identified that affect the formulation of drug candidates into dual-drug loaded nanoparticles, and then screened 176 formulations under different experimental conditions. Based on these experimental data, machine learning methods are applied to pin down the key factors. The implementation of this methodology holds the potential to significantly mitigate the complexities associated with the synthesis of dual-drug loaded nanoparticles, and the co-assembly of these compounds into nanoparticulate systems demonstrates a promising avenue for combination therapy. This approach provides a new strategy for enabling the streamlined, high-throughput screening and synthesis of new nanoscale drug-loaded entities.”
AK010: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK010#h
AK026: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK026#h
Video: https://youtu.be/JjlFvWjl9dY
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PLGA-Rhodamine used in development of micropatches for immunotherapy of cancer.
Thursday, May 30, 2024, 3:40 PM ET
B-Cells are macrophages which play a key role in the immune response. These cells can be leveraged to modify the adaptive immune response. Researchers at Harvard University, used PLGA-Rhodamine (Cat# AV011) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) as part of developing patches to target B-cells and induce them to raise an immune response against cancer. This research holds promise to provide for therapy against cancer. Read more: Prakash, Supriya, Ninad Kumbhojkar, Alexander P. Gottlieb, Kyung-Soo Park, Neha Kapate, and Samir Mitragotri. "Polymer Micropatches as B-Cell Engagers." ACS Applied Materials & Interfaces (2024). https://pubs.acs.org/doi/abs/10.1021/acsami.4c04385
“ABSTRACT: B cells, despite their several unique functionalities, remain largely untapped for use as an adoptive cell therapy and are limited to in vitro use for antibody production. B cells can be easily sourced, they possess excellent lymphoid-homing capabilities, and they can act as antigen-presenting cells (APCs), offering an alternative to dendritic cells (DCs), which have shown limited efficacy in the clinical setting. Soluble factors such as IL-4 and anti-CD40 antibody can enhance the activation, survival, and antigen-presenting capabilities of B cells; however, it is difficult to attain sufficiently high concentrations of these biologics to stimulate B cells in vivo. Micropatches as Cell Engagers (MACE) are polymeric microparticles, surface functionalized with anti-CD40 and anti-IgM, which can attach to B cells and simultaneously engage multiple B-cell receptors (BCR) and CD40 receptors. Stimulation of these receptors through MACE, unlike free antibodies, enhanced the display of costimulatory molecules on the B-cell surface, increased B-cell viability, and improved antigen presentation by B cells to T cells in vitro. B-cell activation by MACE further synergized with soluble IL-4 and anti-CD40. MACE also elicited T-cell chemokine secretion by B cells. Upon intravenous adoptive transfer, MACE-bound B cells homed to the spleen and lymph nodes, key sites for antigen presentation to T cells. Adoptive transfer of MACE-B cells pulsed with the CD4+ and CD8+ epitopes of ovalbumin significantly delayed tumor progression in a murine subcutaneous EG7-OVA tumor model, demonstrating the functional benefit conferred to B cells by MACE. KEYWORDS: B cells, B-cell activation, MACE, APC, cellular vaccine, cancer vaccine”
AV011: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AV011#h
Video: https://youtu.be/XMJp_8qGyZs
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Fluorescent Polylactide from PolySciTech used in development of bioadhesive particles for vaginal infection prevention
Friday, May 17, 2024, 8:23 AM ET
Many sexually transmitted diseases as well as other infections enter by the vaginal route. Providing for a long-acting infection prevention system can reduce exposure and lower the risk of disease. Researchers at Yale University and University of Alabama at Birmingham used PLA-FITC (Cat# AV039) from from PolySciTech Division of Akina, Inc. (www.polyscitech.com) as part of their work in developing mucoadhesive nanoparticles for vaginal protection. This research holds promise to provide for protection from infection. Read more: Grun, Molly K., Praveen Honhar, Yazhe Wang, Samantha Rossano, Minsoo Khang, Hee Won Suh, Krista Fowles et al. "Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation." Bioengineering & Translational Medicine (2024): e10661. https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/btm2.10661
“Long-lasting vaginal dosage forms could improve the therapeutic efficacy of vaginal microbicides, but achieving long-term delivery to the vaginal canal has been a significant challenge. To advance understanding of vaginal dosage retention and biodistribution, we describe a method of noninvasive imaging with 89Zr-labeled bioadhesive nanoparticles (BNPs) in non-human primates. We additionally examined the safety of repeated BNP application. BNPs administered vaginally to cynomolgus monkeys were still detected after 24 h (1.7% retention) and 120 h (0.1% retention). BNPs did not translocate to the uterus or into systemic circulation. Analysis of inflammatory biomarkers in the vaginal fluid and plasma suggest that BNPs are safe and biocompatible, even after multiple doses. BNPs are a promising delivery vehicle for vaginally administered therapeutics. Further studies using the non-human primate imaging materials and methods developed here could help advance clinical translation of BNPs and other long-lasting vaginal dosage forms.”
AV039 (https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AV039#h)
PLGA-Amine from PolySciTech used in development of nanoparticle targeting system for heart therapy.
Friday, May 10, 2024, 4:52 PM ET
Delivery of medicinal molecules to the heart is challenging as many nanoparticles are taken up by either liver or kidney clearance. Researchers at Case Western Reserve University and Bioheights LLC use PLGA-NH2 (catalog AI062) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) in development of fluorescently stained polymer carriers to improve delivery of nanoparticles to cardiovascular tissues. This research holds promise to provide for targeted drug delivery to the heart for treatment of cardiovascular diseases. Read more: Switala, Lauren, Lin Di, Huiyun Gao, Courteney Asase, Matthew Klos, Palanivel Rengasamy, Daria Fedyukina, and Andrei Maiseyeu. "Engineered nanoparticles promote cardiac tropism of AAV vectors." Journal of Nanobiotechnology 22, no. 1 (2024): 223. https://link.springer.com/article/10.1186/s12951-024-02485-6
“Cardiac muscle targeting is a notoriously difficult task. Although various nanoparticle (NP) and adeno-associated viral (AAV) strategies with heart tissue tropism have been developed, their performance remains suboptimal. Significant off-target accumulation of i.v.-delivered pharmacotherapies has thwarted development of disease-modifying cardiac treatments, such as gene transfer and gene editing, that may address both rare and highly prevalent cardiomyopathies and their complications. Here, we present an intriguing discovery: cargo-less, safe poly (lactic-co-glycolic acid) particles that drastically improve heart delivery of AAVs and NPs. Our lead formulation is referred to as ePL (enhancer polymer). We show that ePL increases selectivity of AAVs and virus-like NPs (VLNPs) to the heart and de-targets them from the liver. Serotypes known to have high (AAVrh.74) and low (AAV1) heart tissue tropisms were tested with and without ePL. We demonstrate up to an order of magnitude increase in heart-to-liver accumulation ratios in ePL-injected mice. We also show that ePL exhibits AAV/NP-independent mechanisms of action, increasing glucose uptake in the heart, increasing cardiac protein glycosylation, reducing AAV neutralizing antibodies, and delaying blood clearance of AAV/NPs. Current approaches utilizing AAVs or NPs are fraught with challenges related to the low transduction of cardiomyocytes and life-threatening immune responses; our study introduces an exciting possibility to direct these modalities to the heart at reduced i.v. doses and, thus, has an unprecedented impact on drug delivery and gene therapy. Based on our current data, the ePL system is potentially compatible with any therapeutic modality, opening a possibility of cardiac targeting with numerous pharmacological approaches.”
AI062: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AI062#h
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Fluorescently labelled PLGA from PolySciTech used in development of cell-modulating system for cancer immunotherapy
Wednesday, April 24, 2024, 2:56 PM ET
Delivery of drugs into solid tumors as well as cancers immunosuppressive effect on the surrounding microenvironment makes treatment of cancer challenging. One strategy to overcome this is to utilize a surface-attaching structure which promotes immune cells in the region of cancer to become pro-inflammatory and anti-tumor thus leading the human immune system to fight the cancer. Researchers at Harvard University used PLGA-rhodamine (AV011) and PLGA-Cyanine5 (AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop ‘backpacks’ small structures which attach to myeloid cells and encourages them to participate in immune attack of cancer. This research holds promise to treat many forms of aggressive cancer including immunosuppressive tumors. Read more: Kapate, Neha, Michael Dunne, Alexander P. Gottlieb, Malini Mukherji, Vineeth Chandran Suja, Supriya Prakash, Kyung Soo Park, Ninad Kumbhojkar, Jennifer L. Guerriero, and Samir Mitragotri. "Polymer Backpack‐loaded Tissue Infiltrating Monocytes for Treating Cancer." Advanced Healthcare Materials (2024): 2304144. https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202304144
“Adoptive cell therapies are dramatically altering the treatment landscape of cancer. However, treatment of solid tumors remains a major unmet need, in part due to limited adoptive cell infiltration into the tumor and in part due to the immunosuppressive tumor microenvironment. The heterogeneity of tumors and presence of non-responders also calls for development of antigen-independent therapeutic approaches. Myeloid cells offer such an opportunity, given their large presence in the immunosuppressive tumor microenvironment, such as in triple negative breast cancer. However, their therapeutic utility is hindered by their phenotypic plasticity. Here, we leverage the impressive trafficking ability of adoptively transferred monocytes into the immunosuppressive 4T1 tumor to develop an anti-tumor therapy. To control monocyte differentiation in the tumor microenvironment, we developed surface-adherent “backpacks” stably modified with IFNγ to stimulate macrophage plasticity into a pro-inflammatory, anti-tumor phenotype, a strategy we refer to as Ornate Polymer-backpacks on Tissue Infiltrating Monocytes (OPTIMs). Treatment with OPTIMs substantially reduced tumor burden in a mouse 4T1 model and significant increased survival. Cytokine and immune cell profiling revealed that OPTIMs remodeled the tumor microenvironment into a pro-inflammatory state.”
AV011: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AV011#h
AV034: https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AV034#h
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Video: https://youtu.be/iZWn62jiE_I
mPEG-PLGA from PolySciTech used in development of PARP/Kinase inhibitor drug delivery systems against cancer
Wednesday, March 27, 2024, 1:39 PM ET
There are a wide range of anticancer agents which prevent tumor growth by inhibiting cellular functions. PARP inhibitors, for example, prevent cancer cells from repairing strand breaks in their DNA structures leading to eventual cell death. Additionally, cyclin dependent kinase inhibitors prevent the cell from responding to DNA damage thus amplifying the effect of PARP inhibitors. Drugs based on interfering with the cellular operations of cancer cells can be effective at stopping tumor growth, but can also have serious side effects against healthy cells. Researchers at Northeastern University and Harvard Medical School used mPEG-PLGA (Cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a nanoparticle delivery system combining the effects of a kinase inhibitor and a PARP inhibitor and tested the efficacy of this system against cancer cells. This research holds promise to provide for improved therapy against cancer in the future. Read more: Baldwin, Paige, Shicheng Yang, Adrienne Orriols, Sherrie Wang, Needa Brown, and Srinivas Sridhar. "A nano-cocktail of the PARP inhibitor talazoparib and CDK inhibitor dinaciclib for the treatment of triple negative breast cancer." Cancer Nanotechnology 15, no. 1 (2024): 1-16. https://cancer-nano.biomedcentral.com/articles/10.1186/s12645-023-00240-4
“The addition of the cyclin dependent kinase inhibitor (CDKi) dinaciclib to Poly-(ADP-ribose) polymerase inhibitor (PARPi) therapy is a strategy to overcome resistance to PARPi in tumors that exhibit homologous recombination (HR) deficiencies as well as to expand PARPi therapy to tumors that do not exhibit HR deficiencies. However, combination therapy using pathway inhibitors has been plagued by an inability to administer doses sufficient to achieve clinical benefit due to synergistic toxicities. Here we sought to combine nanoformulations of the PARPi talazoparib, nTLZ, and the CDKi dinaciclib, nDCB, in a nano-cocktail to enhance therapeutic efficacy while maintaining lower doses. Pharmacokinetics of nDCB were assessed to ensure it is compatible with nTLZ. nDCB was combined with nTLZ to generate a nano-cocktail nDCB:nTLZ, which elicits greater cell death in vitro compared to the combination of the free drugs. MDA-MB-231-LUC-D3H2LN xenografts were utilized to assess therapeutic efficacy of the nano-cocktail in terms of tumor progression. Administration of the nano-cocktail significantly slowed tumor progression in the HR proficient animal model compared to administration of free talazoparib and free dinaciclib at the same doses. Histology of the liver, spleen, and kidneys revealed long-term treatment did not induce nanoparticle associated morphological changes. Complete blood count did not reveal any significant hematologic changes after treatment with either the free combination or nano-cocktail. The efficacy and toxicity data suggest that further dose escalation can be pursued in order to achieve a stronger response. These data suggest the administration of combination therapy through the nano-cocktail leads to a better response than the use of free compounds and is a promising strategy for implementing combination therapy in the clinic.”
See more about the mPEG-PLGA used in this study (AK010): https://akinainc.com/polyscitech/products/polyvivo/index.php?highlight=AK010#h
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Video: https://youtu.be/TWB0QxxSUsE
PLGA from PolySciTech used in development of cartilage tissue regeneration for arthritis treatment
Friday, March 22, 2024, 4:36 PM ET
Arthritis is an inflammatory disease that affects about 1 in 5 USA adults (CDC National statistics). The immune system attacks cartilage in the joints which initially causes pain and stiffness but can lead to loss of functionality of the joint. Researchers at Universidade do Porto (Portugal) SINTEF Industry (Norway), Ulm University Medical Center Ulm (Germany), and Askel Healthcare Ltd (Finland) used PLGA from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop anti-inflammatory nanoparticles to work with a scaffold system for treatment of arthritis. This research holds promise to improve treatment of this debilitating disease. Read more: Pereira Vasconcelos, Daniela, Catarina Leite Pereira, Marina Couto, Estrela Neto, Beatriz Ribeiro, Filipe Albuquerque, Alexandra Freitas et al. "Nanoenabled Immunomodulatory Scaffolds for Cartilage Tissue Engineering." Advanced Functional Materials (2024): 2400627. https://onlinelibrary.wiley.com/doi/abs/10.1002/adfm.202400627
“Articular cartilage regeneration is a challenge in tissue engineering. Although diverse materials have been developed for this purpose, cartilage regeneration remains suboptimal. The integration of nanomaterials into 3D network materials holds great potential in the improvement of key mechanical properties, particularly important for osteochondral replacement scaffolds and even to function as carriers for disease-modifying drugs or other regulatory signals. In this study, a simple yet effective cell-free nanoenabled Col-PLA scaffold specially designed to enhance cartilage regeneration and modulate inflammatory response is proposed, by incorporating poly(lactic-co-glycolic acid) (PLGA) ibuprofen nanoparticles (NPs) into a collagen/polylactide (Col-PLA) matrix. The developed nanoenabled scaffold successfully decreases IL-1β release and leads to primary human chondrocytes survival, ultimately restoring extracellular matrix (ECM) production under inflammatory conditions. The nanoenabled Col-PLA scaffolds secretome effectively decreases macrophage invasion in vitro, as well as neutrophil infiltration and inflammatory mediators’, namely the complement component C5/C5a, C-reactive protein, IL-1β, MMP9, CCL20, and CXCL1/KC production in vivo in a rodent air-pouch model. Overall, the established nanoenabled scaffold has the potential to support chondrogenesis as well as modulate inflammatory response, overcoming the limitations of traditional tissue engineering strategies.”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PLGA-Rhodamine from PolySciTech used in development of siRNA-loaded nanoparticles for Alzheimer's treatment.
Tuesday, March 19, 2024, 4:49 PM ET
Alzheimer’s disease is a chronic degenerative disorder characterized by deposition of extracellular amyloid plaques within the brain leading to cognitive decline. Researchers at Korea Institute of Science and Technology, Kyung Hee University, Chungnam National University, Catholic Kwandong University, Soonchunhyang University, and Seoul National University used PLGA-rhodamine (cat# AV027) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles to deliver siRNA. This research holds promise to improve treatment against Alzheimer’s disease. Read more: Shin, Hyo Jung, In Soo Kim, Seung Gyu Choi, Kayoung Lee, Hyewon Park, Juhee Shin, Dayoung Kim et al. "Rejuvenating aged microglia by p16ink4a-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer’s disease." Molecular Neurodegeneration 19, no. 1 (2024): 25. https://link.springer.com/article/10.1186/s13024-024-00715-x
“Age-dependent accumulation of amyloid plaques in patients with sporadic Alzheimer’s disease (AD) is associated with reduced amyloid clearance. Older microglia have a reduced ability to phagocytose amyloid, so phagocytosis of amyloid plaques by microglia could be regulated to prevent amyloid accumulation. Furthermore, considering the aging-related disruption of cell cycle machinery in old microglia, we hypothesize that regulating their cell cycle could rejuvenate them and enhance their ability to promote more efficient amyloid clearance. First, we used gene ontology analysis of microglia from young and old mice to identify differential expression of cyclin-dependent kinase inhibitor 2A (p16ink4a), a cell cycle factor related to aging. We found that p16ink4a expression was increased in microglia near amyloid plaques in brain tissue from patients with AD and 5XFAD mice, a model of AD. In BV2 microglia, small interfering RNA (siRNA)-mediated p16ink4a downregulation transformed microglia with enhanced amyloid phagocytic capacity through regulated the cell cycle and increased cell proliferation. To regulate microglial phagocytosis by gene transduction, we used poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, which predominantly target microglia, to deliver the siRNA and to control microglial reactivity. Nanoparticle-based delivery of p16ink4a siRNA reduced amyloid plaque formation and the number of aged microglia surrounding the plaque and reversed learning deterioration and spatial memory deficits. We propose that downregulation of p16ink4a in microglia is a promising strategy for the treatment of Alzheimer’s disease. Keywords Alzheimer’s disease, Microglia senescence, Phagocytosis, p16ink4a, Cell cycle”
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NEW: Ashland-TM products: https://akinainc.com/polyscitech/products/ashland/
BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
Video: https://youtu.be/86Npj7uCigQ
PLGA from PolySciTech used in development of Ursolic acid delivery nanoparticles for treatment of breast cancer
Thursday, March 7, 2024, 11:33 AM ET
Breast cancer is the most common cancer in women in the United States accounting for approximately 30% of all new female cancers each year (American Cancer Society). Researchers at Mahidol University and Khon Kaen University (Thailand) used PLGA (Cat# AP059) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create and test the efficacy of chitosan-coated nanoparticles loaded with ursolic acid. This research holds promise to provide for improved cancer therapies in the future. Read more: Payomhom, Pattaree, Nattawadee Panyain, Chadamas Sakonsinsiri, Patompon Wongtrakoongate, Kornkamon Lertsuwan, Dakrong Pissuwan, and Kanlaya Prapainop Katewongsa. "Chitosan-Coated Poly (lactic-co-glycolic acid) Nanoparticles Loaded with Ursolic Acid for Breast Cancer Therapy." ACS Applied Nano Materials (2024). https://pubs.acs.org/doi/abs/10.1021/acsanm.3c06161
“Ursolic acid (UA), a pentacyclic triterpenoid found in various fruits and herbs, has the potential as an anticancer agent against multiple cancer types. Nevertheless, its clinical use was limited by its poor water solubility. To overcome this drawback, several nanocarriers were proposed to increase the bioavailability and efficacy of UA. However, the insights into the cellular targets and mechanisms of UA and UA nanoparticles (NPs) remain limited. In this study, chitosan-coated poly(lactic-co-glycolic acid) (PLGA/CS) NPs were loaded with UA. The obtained (UA)-PLGA/CS NPs were spherical with an approximate size of 250 nm and an encapsulation efficiency of 25%. Owing to their promising potential as drug carriers, the NPs were successfully delivered into breast cancer cells (MCF-7 and MDA-MB-231). Moreover, (UA)-PLGA/CS NPs enhanced the anticancer activity of UA, as evidenced by the IC50 values of 26.74 and 40.67 μM in MCF-7 and MDA-MB-231 cells, respectively. These values were lower than those of free UA (90.25 and 85.63 μM in MCF-7 and MDA-MB-231 cells, respectively). The improved cytotoxicity induced by (UA)-PLGA/CS NPs can be attributed to apoptosis induction, collective cell migration and invasion inhibition, and cell proliferation pathway disruption. These findings led to a better understanding of the anticancer effects and molecular mechanisms of (UA)-PLGA/CS NPs and their potential targets for breast cancer therapy. KEYWORDS: ursolic acid nanoparticles PLGA chitosan breast cancer”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PEG-PLGA from PolySciTech used in the development of nanoparticles to deliver anti-tumor agents RG7388 and entinostat for cancer therapy
Thursday, February 22, 2024, 10:18 AM ET
In cancer therapy applications it is possible for specific drugs to work in concert creating a stronger effect than either of them would have on their own. Due to their interactions on several biological pathways, there is good indication that recently discovered RG7388 compound can work with entinostat to treat cancer. Researchers at Queen’s University Belfast and Al-Ahliyya Amman University used PEG-PLGA (Cat# AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create and test the efficacy of nanoparticles loaded with both drugs. This research holds promise to improve cancer therapy in the future. Read more: Abed, Anas, Michelle K. Greene, Alhareth A. Alsa’d, Andrea Lees, Andrew Hindley, Daniel B. Longley, Simon S. McDade, and Christopher J. Scott. "Nanoencapsulation of MDM2 Inhibitor RG7388 and Class-I HDAC Inhibitor Entinostat Enhances their Therapeutic Potential Through Synergistic Antitumor Effects and Reduction of Systemic Toxicity." Molecular Pharmaceutics (2024). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.3c00926
“Inhibitors of the p53–MDM2 interaction such as RG7388 have been developed to exploit latent tumor suppressive properties in p53 in 50% of tumors in which p53 is wild-type. However, these agents for the most part activate cell cycle arrest rather than death, and high doses in patients elicit on-target dose-limiting neutropenia. Recent work from our group indicates that combination of p53–MDM2 inhibitors with the class-I HDAC inhibitor Entinostat (which itself has dose-limiting toxicity issues) has the potential to significantly augment cell death in p53 wild-type colorectal cancer cells. We investigated whether coencapsulation of RG7388 and Entinostat within polymeric nanoparticles (NPs) could overcome efficacy and toxicity limitations of this drug combination. Combinations of RG7388 and Entinostat across a range of different molar ratios resulted in synergistic increases in cell death when delivered in both free drug and nanoencapsulated formats in all colorectal cell lines tested. Importantly, we also explored the in vivo impact of the drug combination on murine blood leukocytes, showing that the leukopenia induced by the free drugs could be significantly mitigated by nanoencapsulation. Taken together, this study demonstrates that formulating these agents within a single nanoparticle delivery platform may provide clinical utility beyond use as nonencapsulated agents. KEYWORDS:cancer nanoparticles Entinostat nutlin toxicity combination therapy”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PLGA-PEG-Dibenzocyclooctyne from PolySciTech used in research on PARPi treatment for ovarian cancer.
Friday, February 16, 2024, 4:21 PM ET
On average, about 12,740 women die from ovarian cancer each year in USA (American Cancer Society).Researchers at University of Maryland used PLGA-PEG-COOH (AI171) and PLGA-PEG-DBCO (AI205) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop nanoparticles loaded with talazoparib as a strategy to treat chemotherapy resistant ovarian cancer. This research holds promise to improve cancer therapy in the future. Read more: Sorrin, Aaron, Anika Dasgupta, Kathryn McNaughton, Carla Arnau Del Valle, Keri Zhou, Cindy Liu, Dana M. Roque, and Huang Chiao Huang. "Co-Packaged PARP inhibitor and photosensitizer for targeted photo-chemotherapy of 3D ovarian cancer spheroids." Cell & Bioscience 14, no. 1 (2024): 1-13. https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-024-01197-6
“Background: Within the last decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have emerged in the clinic as an effective treatment for numerous malignancies. Preclinical data have demonstrated powerful combination effects of PARPi paired with photodynamic therapy (PDT), which involves light-activation of specialized dyes (photosensitizers) to stimulate cancer cell death through reactive oxygen species generation. Results: In this report, the most potent clinical PARP inhibitor, talazoparib, is loaded into the core of a polymeric nanoparticle (NP-Tal), which is interfaced with antibody-photosensitizer conjugates (photoimmunoconjugates, PICs) to form PIC-NP-Tal. In parallel, a new 3D fluorescent coculture model is developed using the parental OVCAR-8-DsRed2 and the chemo-resistant subline, NCI/ADR-RES-EGFP. This model enables quantification of trends in the evolutionary dynamics of acquired chemoresistance in response to various treatment regimes. Results reveal that at a low dosage (0.01 μM), NP-Tal kills the parental cells while sparing the chemo-resistant subline, thereby driving chemoresistance. Next, PIC-NP-Tal and relevant controls are evaluated in the 3D coculture model at multiple irradiation doses to characterize effects on total spheroid ablation and relative changes in parental and subline cell population dynamics. Total spheroid ablation data shows potent combination effects when PIC and NP-Tal are co-administered, but decreased efficacy with the conjugated formulation (PIC-NP-Tal). Analysis of cell population dynamics reveals that PIC, BPD + NP-Tal, PIC + NP-Tal, and PIC-NP-Tal demonstrate selection pressures towards chemoresistance. Conclusions: This study provides key insights into manufacturing parameters for PARPi-loaded nanoparticles, as well as the potential role of PDT-based combination therapies in the context of acquired drug resistance.”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PLGA-Rhodamine from PolySciTech used in research on cancer-targeting nanoparticles
Friday, February 16, 2024, 4:20 PM ET
Paclitaxel is a chemotherapeutic agent which prevents cellular growth. Due to its non-specific nature, it damages both healthy and cancerous cells which leads to significant side-effects. Researchers at Purdue University used PLGA-rhodamine (AV011) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to develop ATP targeted nanoparticles for localization of PTX at a cancer site and to recruit immune cells to the cancer. This research holds promise to improve cancer therapy in the future. Read more: Kwon, Soonbum, Fanfei Meng, Hassan Tamam, Hytham H. Gadalla, Jianping Wang, Boyang Dong, Amber S. Hopf Jannasch, Timothy L. Ratliff, and Yoon Yeo. "Systemic Delivery of Paclitaxel by Find-Me Nanoparticles Activates Antitumor Immunity and Eliminates Tumors." ACS nano (2024). https://pubs.acs.org/doi/abs/10.1021/acsnano.3c11445
“Local delivery of immune-activating agents has shown promise in overcoming an immunosuppressive tumor microenvironment (TME) and stimulating antitumor immune responses in tumors. However, systemic therapy is ultimately needed to treat tumors that are not readily locatable or accessible. To enable systemic delivery of immune-activating agents, we employ poly(lactic-co-glycolide) (PLGA) nanoparticles (NPs) with a track record in systemic application. The surface of PLGA NPs is decorated with adenosine triphosphate (ATP), a damage-associated molecular pattern to recruit antigen-presenting cells (APCs). The ATP-conjugated PLGA NPs (NPpD-ATP) are loaded with paclitaxel (PTX), a chemotherapeutic agent inducing immunogenic cell death to generate tumor antigens in situ. We show that the NPpD-ATP retains ATP activity in hostile TME and provides a stable “find-me” signal to recruit APCs. Therefore, the PTX-loaded NPpD-ATP helps populate antitumor immune cells in TME and attenuate the growth of CT26 and B16F10 tumors better than a mixture of PTX-loaded NPpD and ATP. Combined with anti-PD-1 antibody, PTX-loaded NPpD-ATP achieves complete regression of CT26 tumors followed by antitumor immune memory. This study demonstrates the feasibility of systemic immunotherapy using a PLGA NP formulation that delivers ICD-inducing chemotherapy and an immunostimulatory signal. chemoimmunotherapy systemic delivery PLGA nanoparticles adenosine triphosphate immunogenic cell death paclitaxel”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PLGA from PolySciTech used in development of oral delivery system for liraglutide
Friday, February 16, 2024, 4:19 PM ET
Liraglutide is a GLP-1 analog which provides for treatment of diabetes. Due to it’s low bioavailability, it can not be normally administered orally. Recently, researchers at Yantai University utilized PLGA (AP040) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to develop oral delivery nanoparticles for liraglutide treatment of diabetes. This research holds promise to treat this chronic disease. Read more: Zhao, Zhenyu, Ruihuan Ding, Yumei Wang, Ranran Yuan, Houqian Zhang, Tianyang Li, Wei Zheng, Entao Chen, Aiping Wang, and Yanan Shi. "Sulfobetaine modification of poly (D, l-lactide-co-glycolic acid) nanoparticles enhances mucus permeability and improves bioavailability of orally delivered liraglutide." Journal of Drug Delivery Science and Technology (2024): 105437. https://www.sciencedirect.com/science/article/pii/S1773224724001059
“The glucagon-like peptide-1 (GLP-1) analogue used to treat diabetes is an increasingly popular polypeptide protein therapeutic, commonly marketed as an injection. However, the effective oral administration of peptide drugs remains challenging because of their extremely low bioavailability. In recent years, a number of delivery systems that have been shown to be effective in improving the therapeutic efficacy of oral drugs. Herein, liraglutide was employed as a model drug and amphoteric sulfobetaine (SB12) was selected for the surface modification of poly (D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NPs) to obtain hydrophilic and electroneutral SB12-NPs. The functional SB12-NPs were first screened to identify the optimal prescription process and obtained from the final prescription were evaluated. The particle size, zeta potential, encapsulation efficiency (EE%) and drug-loading (DL%) of SB12-NPs were 87.25 ± 0.77 nm, −3.91 ± 1.88 mV, 77.45% ± 1.62%, and 10.46% ± 0.21%, respectively. The cellular uptake of Lira-SB12 NPs was significantly better than that of free liraglutide, and verified that it was transported mainly through endocytosis mediated by clathrin- and lipid raft–mediated. The trans-mucous permeability (2.86-fold) and intestinal permeability (1.79-fold) of SB12-NPs were significantly higher than those of free liraglutide. Single and multiple doses of SB12-NPs showed that the blood sugar level of diabetic mice could be lower to about 70% of the initial value. The SB12-NPs demonstrated a higher relative bioavailability of 9.59% compared with that of oral pure liraglutide (5.13%). Thus, SB12-modified PLGA NPs with hydrophilic and electroneutral surface properties can significantly improve mucus permeability and oral bioavailability, and have the potential to be applied for oral delivery of peptides and proteins.”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PGACL from PolySciTech used in development of flexible electronics for implantable devices
Tuesday, February 6, 2024, 4:54 PM ET
“Highlights: The paper introduces a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), with remarkable mechanical properties, including high elongation-at-break (< 1300%), resilience, and toughness (75 MJ m−3) for soft and transient electronics. Fabrication of conducting polymers with PGCL yields stretchable, conductive composites for transient electronic devices, functioning reliably under external strains. The study demonstrates the feasibility of a disintegrable electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds on soft, time-dynamic tissues or versatile biomedical areas of interest. Substrates or encapsulants in soft and stretchable formats are key components for transient, bioresorbable electronic systems; however, elastomeric polymers with desired mechanical and biochemical properties are very limited compared to non-transient counterparts. Here, we introduce a bioresorbable elastomer, poly(glycolide-co-ε-caprolactone) (PGCL), that contains excellent material properties including high elongation-at-break (< 1300%), resilience and toughness, and tunable dissolution behaviors. Exploitation of PGCLs as polymer matrices, in combination with conducing polymers, yields stretchable, conductive composites for degradable interconnects, sensors, and actuators, which can reliably function under external strains. Integration of device components with wireless modules demonstrates elastic, transient electronic suture system with on-demand drug delivery for rapid recovery of post-surgical wounds in soft, time-dynamic tissues. Biodegradable elastomer; Conductive polymer composites; Biomedical device; Transient electronics”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
Fluorescently labelled PLGA from PolySciTech used in development of oral semaglutide delivery system
Wednesday, January 31, 2024, 11:24 AM ET
Diabetes is a widespread disease affecting roughly 38.4 million people of all ages. GLP1 analog semaglutide can be utilized to treat diabetes. Researchers from Universidade do Porto (Portugal), University of Groningen (Netherlands), Novo Nordisk, KTH Royal Institute of Technology, Uppsala University (Sweden), and University of Helsinki (Finland), used fluorescent PLGA-FKR648 (cat# AV015) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to develop oral delivery nanoparticles for semaglutide treatment of diabetes. This research holds promise to improve diabetes treatment. Read more: Pinto, Soraia, Mahya Hosseini, Stephen T. Buckley, Wen Yin, Javad Garousi, Torbjörn Gräslund, Sven van Ijzendoorn, Hélder A. Santos, and Bruno Sarmento. "Nanoparticles targeting the intestinal Fc receptor enhance intestinal cellular trafficking of semaglutide." Journal of Controlled Release 366 (2024): 621-636. https://www.sciencedirect.com/science/article/pii/S0168365924000191
“Highlights: Semaglutide was successfully incorporated into FcRn-targeted polymeric nanoparticles. FcRn-targeted nanoparticles bound to hFcRn in a pH-dependent manner, with a stronger interaction at pH 6 than at pH 7.4. FcRn-targeted nanoparticles showed higher interaction with in vitro intestinal models than non-targeted nanoparticles. Injection of nanomedicines into intestinal organoids' lumen is a promising tool to evaluate cell-nanopartices interaction. Abstract: Semaglutide is the first oral glucagon-like peptide-1 (GLP-1) analog commercially available for the treatment of type 2 diabetes. In this work, semaglutide was incorporated into poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (NPs) to improve its delivery across the intestinal barrier. The nanocarriers were surface-decorated with either a peptide or an affibody that target the human neonatal Fc receptor (hFcRn), located on the luminal cell surface of the enterocytes. Both ligands were successfully conjugated with the PLGA-PEG via maleimide-thiol chemistry and thereafter, the functionalized polymers were used to produce semaglutide-loaded NPs. Monodisperse NPs with an average size of 170 nm, neutral surface charge and 3% of semaglutide loading were obtained. Both FcRn-targeted NPs exhibited improved interaction and association with Caco-2 cells (cells that endogenously express the hFcRn), compared to non-targeted NPs. Additionally, the uptake of FcRn-targeted NPs was also observed to occur in human intestinal organoids (HIOs) expressing hFcRn through microinjection into the lumen of HIOs, resulting in potential increase of semaglutide permeability for both ligand-functionalized nanocarriers. Herein, our study demonstrates valuable data and insights that the FcRn-targeted NPs has the capacity to promote intestinal absorption of therapeutic peptides.”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
Video: https://youtu.be/wpexfgqfnL0
mPEG-PLGA from PolySciTech used in development of brusatol/docetaxel nanoparticles for prostate cancer treatment
Wednesday, January 31, 2024, 11:23 AM ET
Prostate cancer is the second leading cause of cancer death in American men and 12.9% of men will be diagnosed with this disease during their lifetime. Researchers at Howard University used mPEG-PLGA (cat# AK029) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to make nanoparticles loaded with brusatol and docetaxel. This research holds promise to improve prostate cancer treatment in the future. Read more: Adekiya, Tayo Alex, Madison Moore, Michael Thomas, Gabriel Lake, Tamaro Hudson, and Simeon K. Adesina. "Preparation, Optimization, and In-Vitro Evaluation of Brusatol-and Docetaxel-Loaded Nanoparticles for the Treatment of Prostate Cancer." Pharmaceutics 16, no. 1 (2024): 114. https://www.mdpi.com/1999-4923/16/1/114
“Abstract: Challenges to docetaxel use in prostate cancer treatment include several resistance mechanisms as well as toxicity. To overcome these challenges and to improve the therapeutic efficacy in heterogeneous prostate cancer, the use of multiple agents that can destroy different subpopulations of the tumor is required. Brusatol, a multitarget inhibitor, has been shown to exhibit potent anticancer activity and play an important role in drug response and chemoresistance. Thus, the combination of brusatol and docetaxel in a nanoparticle platform for the treatment of prostate cancer is expected to produce synergistic effects. In this study, we reported the development of polymeric nanoparticles for the delivery of brusatol and docetaxel in the treatment of prostate cancer. The one-factor-at-a-time method was used to screen for formulation and process variables that impacted particle size. Subsequently, factors that had modifiable effects on particle size were evaluated using a 24 full factorial statistical experimental design followed by the optimization of drug loading. The optimization of blank nanoparticles gave a formulation with a mean size of 169.1 nm ± 4.8 nm, in agreement with the predicted size of 168.333 nm. Transmission electron microscopy showed smooth spherical nanoparticles. The drug release profile showed that the encapsulated drugs were released over 24 h. Combination index data showed a synergistic interaction between the drugs. Cell cycle analysis and the evaluation of caspase activity showed differences in PC-3 and LNCaP prostate cancer cell responses to the agents. Additionally, immunoblots showed differences in survivin expression in LNCaP cells after treatment with the different agents and formulations for 24 h and 72 h. Therefore, the nanoparticles are potentially suitable for the treatment of advanced prostate cancer. keywords: prostate cancer; docetaxel; brusatol; nanoparticles; cell cycle; caspase activity; surviving.”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
Video: https://youtu.be/SCy96Ils4PQ
PLGA from PolySciTech used in development of cell membrane-derived nanoparticle for cancer immunotherapy
Thursday, January 18, 2024, 4:53 PM ET
The human immune system is extremely powerful though most forms of cancer have developed ways to evade it. Researchers at University of Texas at Arlington and Southwestern Medical Center Used PLGA (Cat# AP082) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to create particles with HER2 specific coating. These particles localized in tumor areas and delivered cisplatin. This research holds promise to improve therapy against cancer in the future. Read more: Yaman, Serkan, Harish Ramachandramoorthy, Priyanka Iyer, Uday Chintapula, Tam Nguyen, Manoj Sabnani, Tanviben Kotadia et al. "Targeted chemotherapy via HER2-based chimeric antigen receptor (CAR) engineered T-cell membrane coated polymeric nanoparticles." Bioactive Materials 34 (2024): 422-435. https://www.sciencedirect.com/science/article/pii/S2452199X23004309
“Highlights: Membrane coating aids camouflage Nanoparticle delivery. CAR-T based receptor increases targeting towards Non-small cell lung cancer. Paves new strategy for Syngenic cancer therapeutics. Abstract: Cell membrane-derived nanoparticles (NPs) have recently gained popularity due to their desirable features in drug delivery such as mimicking properties of native cells, impeding systemic clearance, and altering foreign body responses. Besides NP technology, adoptive immunotherapy has emerged due to its promise in cancer specificity and therapeutic efficacy. In this research, we developed a biomimetic drug carrier based on chimeric antigen receptor (CAR) transduced T-cell membranes. For that purpose, anti-HER2 CAR-T cells were engineered via lentiviral transduction of anti-HER2 CAR coding lentiviral plasmids. Anti-HER2 CAR-T cells were characterized by their specific activities against the HER2 antigen and used for cell membrane extraction. Anti-cancer drug Cisplatin-loaded poly (D, l-lactide-co-glycolic acid) (PLGA) NPs were coated with anti-human epidermal growth factor receptor 2 (HER2)-specific CAR engineered T-cell membranes. Anti-HER2 CAR-T-cell membrane-coated PLGA NPs (CAR-T-MNPs) were characterized and confirmed via fluorescent microscopy and flow cytometry. Membrane-coated NPs showed a sustained drug release over the course of 21 days in physiological conditions. Cisplatin-loaded CAR-T-MNPs also inhibited the growth of multiple HER2+ cancer cells in vitro. In addition, in vitro uptake studies revealed that CAR-T-MNPs showed an increased uptake by A549 cells. These results were also confirmed via in vivo biodistribution and therapeutic studies using a subcutaneous lung cancer model in nude mice. CAR-T-MNPs localized preferentially at tumor areas compared to those of other studied groups and consisted of a significant reduction in tumor growth in tumor-bearing mice. In Conclusion, the new CAR modified cell membrane-coated NP drug-delivery platform has demonstrated its efficacy both in vitro and in vivo. Therefore, CAR engineered membrane-coated NP system could be a promising cell-mimicking drug carrier that could improve therapeutic outcomes of lung cancer treatments.”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PEG-PLGA from PolySciTech used in development of nanoparticles to treat stroke-induced brain injury
Friday, January 12, 2024, 2:04 PM ET
In 2021, 1 out of every 6 deaths from cardiovascular disease was caused by stroke and 87% of all strokes are ischemic strokes (https://www.cdc.gov/stroke/facts.htm). In addition to loss of blood-flow during ischemic stroke, brain damage is further aggravated by inflammation and other physiological responses. By reducing the inflammatory response, the damage from a stroke can be mitigated. Researchers at Chungnam National University, The University of Alabama, Mayo Clinic, Dankook University, Kyungpook National University, Indiana University School of Medicine, Seoul National University, Hallym University, Konyang University, Ajou University, Chungnam National University, and The University of Alabama used PLGA-PEG-COOH (AI078) and mPEG-PLGA (AK037) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to develop nanoparticles decorated with AstroLa peptide for targeting to stroke-damaged portions of the brain and reducing inflammation. This research holds promise to reduce the damage resulting from an often fatal disease. Read more: Shin, Hyo Jung, Seung Gyu Choi, Fengrui Qu, Min-Hee Yi, Choong-Hyun Lee, Sang Ryong Kim, Hyeong-Geug Kim et al. "Peptide-mediated targeted delivery of SOX9 nanoparticles into astrocytes ameliorates ischemic brain injury." Nanoscale (2024). https://pubs.rsc.org/en/content/articlehtml/2023/nr/d3nr01318a
“Abstract: Astrocytes are highly activated following brain injuries, and their activation influences neuronal survival. Additionally, SOX9 expression is known to increase in reactive astrocytes. However, the role of SOX9 in activated astrocytes following ischemic brain damage has not been clearly elucidated yet. Therefore, in the present study, we investigated the role of SOX9 in reactive astrocytes using a poly-lactic-co-glycolic acid (PLGA) nanoparticle plasmid delivery system in a photothrombotic stroke animal model. We designed PLGA nanoparticles to exclusively enhance SOX9 gene expression in glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Our observations indicate that PLGA nanoparticles encapsulated with GFAP:SOX9:tdTOM reduce ischemia-induced neurological deficits and infarct volume through the prostaglandin D2 pathway. Thus, the astrocyte-targeting PLGA nanoparticle plasmid delivery system provides a potential opportunity for stroke treatment. Since the only effective treatment currently available is reinstating the blood supply, cell-specific gene therapy using PLGA nanoparticles will open a new therapeutic paradigm for brain injury patients in the future.”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PLGA from PolySciTech used for temporary fluorescent marking of patients for record keeping to prevent medical errors.
Friday, January 12, 2024, 2:03 PM ET
Studies of medical errors indicate that as many as 251,000 deaths occur annually in the United States as a result of these errors (https://pubmed.ncbi.nlm.nih.gov/28186008/). Tools which enable easy, quick, and temporary recording of patient data can reduce these errors. Researchers at Massachusetts Institute of Technology, University of Melbourne, and Global Health Labs used PLGA (AP022) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to create quantum-dot loaded microneedles. These provide for a fluorescent tracer embedded in patient skin which slowly degrades away after the mark is no longer needed. By coding this marker to represent relevant patient health data, costly and potentially dangerous medical mistakes can be prevented. Read more: Collins, Joe, Jooli Han, Morteza Sarmadi, Stephanie Allison‐Logan, Aurelien vander Straeten, Collin F. Perkinson, Sarah Acolaste et al. "On‐Patient Temporary Medical Record for Accurate, Time‐Sensitive Information at the Point of Care." Advanced Functional Materials (2024): 2311821. https://onlinelibrary.wiley.com/doi/pdf/10.1002/adfm.202311821
“Accurate medical recordkeeping is important for personal and public health. Conventional forms of on-patient medical information, such as medical alert bracelets or finger-markings, may compromise patient privacy because they are readily visible to other people. Here, the development of an invisible, temporary, and easily deployable on-patient medical recordkeeping system is reported. Information is stored in unique patterns of spatially distributed near-infrared (NIR) fluorescent quantum dots (QDs), which are delivered to the skin using dissolvable microneedle arrays. The patterns are invisible to the naked eye but detectable with an infrared camera, which can extract information with >98% accuracy using automated pattern recognition software. By encapsulating NIR QDs in an FDA-approved biodegradable polymer, biodegradation rates can be tuned so that the encoded medical information can be conveyed in both a spatial and temporal manner, with some components fading within 100 days and others persisting for 6 months. This may be particularly useful for administering a series of vaccinations or treatments by indicating if enough time has passed for the patient to receive the next dose. Importantly, this system contains no personal information, does not require connection to a centralized database, and is not visible to the naked eye, ensuring patient privacy.”
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BPR (Biotech Pharma Research) Conference (April 10, 2024, KPTC West Lafayette, IN) is a free scientific/networking conference hosted by Akina (http://bprconference.com/).
PLGA from PolySciTech used in development of printable antibiotic coatings for orthopedic implants
Wednesday, January 3, 2024, 11:48 AM ET
Infections associated with surgical implantation can lead to significant patient morbidity and costs for extended treatment of the bacterial infection. The incidence of this varies but has been reported to be ~ 5.3% of cases with Staphylococcus aureus being the most common bacteria (https://pubmed.ncbi.nlm.nih.gov/28712173/). Researchers at Warsaw University of Technology, University of Helsinki, and Medical University of Warsaw used PLGA (AP081, AP041) from PolySciTech Division of Akina, Inc (www.polyscitech.com) to create a printable formulation of antimicrobial releasing surface coating for orthopedic implants. This research holds promise to reduce surgical infections from implant placement. Martinez Perez, David, Ines Reigada, Jayendra Z Patel, Jari Yli-Kauhaluoma, Leena Hanski, Michał Srebrzynski, Maciej Spychalski, Emilia Choinska, Adyary Fallarero, and Wojciech Święszkowski. "Drop on Demand Antimicrobial Printed Coatings Loaded with Dehydroabietic Acid Derivative to Prevent Orthopedic Implant Infections." Available at SSRN 4633087. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4633087
“For the first time, microvalve-based drop on demand (DOD) printing technology has been applied to develop antimicrobial coatings for orthopedic implants. Leveraging the highprecision deposition capabilities of DOD, coatings loaded with a novel biofilm inhibitor, N- (abiet-8,11,13-trien-18-oyl) cyclohexyl-L-alanine (DHA1), were fabricated on titanium coupons. The PLGA-PEG-DHA1 coatings exhibited significant efficacy in preventing Staphylococcus aureus adhesion, both in monoculture and in co-culture with HL-60 cells. Furthermore, the PLGA-PEGDHA1 coatings showed a sustained protective effect of the 30% DHA1-loaded coating over a 24- hour period. The PLGA-PEG-DHA1 coatings ensured safety with no cytotoxic effect observed on SaOS-2 mammalian cells, fostering tissue integration post-implantation. This study paves the way to produce multi-component DOD coatings combining various ink compositions, including different polymers, antimicrobial agents, or growth factors.”
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PLGA-Rhodamine used in development of macrophage backpacks for anti-inflammatory applications
Monday, December 18, 2023, 4:21 PM ET
Brain injury is often made worse by subsequent inflammation which exasperates existing damage. Mitigating this inflammation can provide a valuable tool for trauma treatment. Researchers at Harvard University and Massachusetts General Hospital used PLGA-Rhodamine (cat# AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of development of immune-cell targeting particles for treatment of inflammation. This research holds promise to treat excess inflammation and subsequent damage. Kapate, Neha, Rick Liao, Ryan Luke Sodemann, Tawny Stinson, Supriya Prakash, Ninad Kumbhojkar, Vineeth Chandran Suja et al. "Backpack-mediated anti-inflammatory macrophage cell therapy for the treatment of traumatic brain injury." PNAS Nexus (2023): pgad434. https://academic.oup.com/pnasnexus/advance-article-pdf/doi/10.1093/pnasnexus/pgad434/54408201/pgad434.pdf
“Abstract: Traumatic brain injury (TBI) is a debilitating disease with no current therapies outside of acute clinical management. While acute, controlled inflammation is important for debris clearance and regeneration after injury, chronic, rampant inflammation plays a significant adverse role in the pathophysiology of secondary brain injury. Immune cell therapies hold unique therapeutic potential for inflammation modulation, due to their active sensing and migration abilities. Macrophages are particularly suited for this task, given the role of macrophages and microglia in the dysregulated inflammatory response after TBI. However, maintaining adoptively transferred macrophages in an anti-inflammatory, wound-healing phenotype against the pro-inflammatory TBI milieu is essential. To achieve this, we developed discoidal microparticles, termed backpacks, encapsulating anti-inflammatory interleukin-4 and dexamethasone for ex vivo macrophage attachment. Backpacks durably adhered to the surface of macrophages without internalization and maintained an anti-inflammatory phenotype of the carrier macrophage through 7 days in vitro. Backpack-macrophage therapy was scaled up and safely infused into piglets in a cortical impact TBI model. Backpack-macrophages migrated to the brain lesion site and reduced pro-inflammatory activation of microglia in the lesion penumbra of the rostral gyrus of the cortex and decreased serum concentrations of pro-inflammatory biomarkers. These immunomodulatory effects elicited a 56% decrease in lesion volume. The results reported here demonstrate, to the best of our knowledge, the first use of a cell therapy intervention for a large animal model of TBI and highlight the potential of macrophage-based therapy. Further investigation is required to elucidate the neuroprotection mechanisms associated with anti-inflammatory macrophage therapy.”
PLGA-Rhodamine from PolySciTech used in research on magnetic nanoparticles for magnetic-based cellular targeting.
Wednesday, December 13, 2023, 3:32 PM ET
One way to deliver drugs to the desired location in a body
is to attach them via small particles, or backpacks, to macrophage cells which
are travelling to that section. Notably, this can be utilized to treat cancer
which is highly difficult to get drug molecules into the right location. Researchers
at University of Colorado Boulder, University of Florida used PLGA-Rhodamine (AV011) from PolySciTech
division of Akina, Inc. (www.polyscitech.com)
as part of creating magnetic backpacks to specifically bind to cellular
components. This research holds promise to provide for an additional cancer
treatment option. Read more: Day, Nicole B., Christopher R. Orear, Ambar C.
Velazquez-Albino, Hayden J. Good, Andrii Melnyk, Carlos M. Rinaldi-Ramos, and
C. Wyatt Shields IV. "Magnetic Cellular Backpacks for Spatial Targeting,
Imaging, and Immunotherapy." ACS Applied Bio Materials (2023). https://pubs.acs.org/doi/abs/10.1021/acsabm.3c00720
“Adoptive cell transfer (ACT) therapies are growing in
popularity due to their ability to interact with diseased tissues in a specific
manner. Disc-shaped particles, or “backpacks”, that bind to cellular surfaces
show promise for augmenting the therapeutic potential of adoptively transferred
cells by resisting phagocytosis and locally releasing drugs to maintain
cellular activity over time. However, many ACTs suffer from limited tumor
infiltration and retention and lack a method for real-time spatial analysis.
Therefore, we have designed biodegradable backpacks loaded with
superparamagnetic iron oxide nanoparticles (SPIONs) to improve upon current ACT
strategies by (i) controlling the localization of cell-backpack complexes using
gradient magnetic fields and (ii) enabling magnetic particle imaging (MPI) to
track complexes after injection. We show that magnetic backpacks bound to
macrophages and loaded with a proinflammatory drug, resiquimod, maintain
anticancer phenotypes of carrier macrophages for 5 days and create cytokine
“factories” that continuously release IL-12. Furthermore, we establish that
forces generated by gradient magnet fields are sufficient to displace
cell-backpack complexes in physiological settings. Finally, we demonstrate that
MPI can be used to visualize cell-backpack complexes in mouse tumors, enabling
a potential strategy to track the biodistribution of ACTs in real time. KEYWORDS:
adoptive cell transfer immunotherapy cancer drug delivery macrophage
microparticle magnetic particle imaging”
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These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.39190006256104 seconds)
