Monday, July 8, 2024

PLA-PEG-PLA thermogel from PolySciTech used in development of celecoxib delivery system for treatment of breast cancer

 


Breast cancer accounts for 30% of all new cancers in women. There are 670,000 deaths per year due to this disease. Researchers at University of Oklahoma, Medical College of Wisconsin, and Thomas Jefferson University used PLA-PEG-PLA (cat# AK100) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a thermally responsive hydrogel as a carrier of nanoparticles for delivery of celecoxib. This research holds promise to provide for improved treatment of breast cancer. Read more: Simmons, Reese, Hiroyasu Kameyama, Seiko Kubota, Yunguang Sun, John F. Langenheim, Rana Ajeeb, Tristan S. Shao et al. "Sustained delivery of celecoxib from nanoparticles embedded in hydrogel injected into the biopsy cavity to prevent biopsy-induced breast cancer metastasis." Breast Cancer Research and Treatment (2024): 1-13. https://link.springer.com/article/10.1007/s10549-024-07410-x

“Purpose: We have previously reported that protracted Cyclooxygenase-2 (COX-2) activity in bone marrow-derived cells (BMDCs) infiltrating into biopsy wounds adjacent to the biopsy cavity of breast tumors in mice promotes M2-shift of macrophages and pro-metastatic changes in cancer cells, effects which were suppressed by oral administration of COX-2 inhibitors. Thus, local control of COX-2 activity in the biopsy wound may mitigate biopsy-induced pro-metastatic changes. Methods: A combinatorial delivery system—thermosensitive biodegradable poly(lactic acid) hydrogel (PLA-gel) incorporating celecoxib-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Cx-NP/PLA-gel)—was injected into the biopsy cavity of Py230 murine breast tumors to achieve local control of COX-2 activity in the wound stroma. Results: A single intra-biopsy cavity injection of PLA-gel loaded with rhodamine-encapsulated nanoparticles (NPs) showed sustained local delivery of rhodamine preferentially to infiltrating BMDCs with minimal to no rhodamine uptake by the reticuloendothelial organs in mice. Moreover, significant reductions in M2-like macrophage density, cancer cell epithelial-to-mesenchymal transition, and blood vessel density were observed in response to a single intra-biopsy cavity injection of Cx-NP/PLA-gel compared to PLA-gel loaded with NPs containing no payload. Accordingly, intra-biopsy cavity injection of Cx-NP/PLA-gel led to significantly fewer metastatic cells in the lungs than control-treated mice. Conclusion: This study provides evidence for the feasibility of sustained, local delivery of payload preferential to BMDCs in the wound stroma adjacent to the biopsy cavity using a combinatorial delivery system to reduce localized inflammation and effectively mitigate breast cancer cell dissemination. Keywords: Hydrogel, Nanoparticle, Metastasis, Biopsy, Biopsy site marker, Local drug delivery”

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Monday, July 1, 2024

mPEG-PLGA from PolySciTech used in development of RNA delivery system for control of gene expression

 


As a general rule, DNA is transcribed into single-stranded RNA which is then used to manufacture proteins. The original DNA of a cell is generally set and can not be easily edited however RNA is a dynamic process in which the single-stranded ‘message-carrier’ is constantly created, used, and destroyed. By applying messenger RNA (mRNA for transcription) of a wanted protein and silencing RNA (siRNA which selectively binds to specific coding of mRNA to prevent it from being converted to a protein) it is possible to control the expression of genes at a cellular level for a fixed period of time. Researchers at University of Ottawa used mPEG-PLGA (AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles for the simultaneous delivery of mRNA and siRNA to control gene/protein expression. This research holds promise to provide for treatment of a wide range of diseases. Read more: Manturthi, Shireesha, Sara El-Sahli, Yuxia Bo, Emma Durocher, Melanie Kirkby, Alyanna Popatia, Karan Mediratta et al. "Nanoparticles co-delivering siRNA and mRNA for simultaneous restoration and silencing of gene/protein expression in vitro and in vivo." bioRxiv (2024): 2024-06. https://www.biorxiv.org/content/10.1101/2024.06.22.600196.abstract

“RNA-based agents such as siRNA, miRNA, and mRNA can selectively manipulate gene expression/proteins and have the potential to revolutionize the current therapeutic strategies for various diseases, including cancer. To address the poor stability and inherent limitations of RNA agents, nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside the cells. Recent studies have focused on either siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, complex diseases like cancer need multi-targeted approaches to selectively target multiple gene expressions/proteins. In this proof-of-concept study, we developed co-delivery nanoparticles containing Luc-mRNA and siRNA-GFP as model RNA agents ((M+S)-NPs) and assessed their effects in vitro and in vivo. Our studies show that NPs can effectively deliver both functional mRNA and siRNA together, simultaneously impacting the expression of two genes/proteins in vitro. Additionally, after in vivo administration, co-delivery NPs successfully knocked down GFP while introducing luciferase in a TNBC mouse model, indicating our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted, multi-delivery approaches for complex diseases like cancer. Keywords: nanoparticles, siRNA, mRNA, co-delivery, gene, protein, restoration and knockdown.”

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Thursday, June 27, 2024

PLGA-PEG-PLGA from PolySciTech used in development of ocular release platform for treatment of secondary cataracts

 

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.”

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Wednesday, June 26, 2024

PLGA from PolySciTech used in development of anti-viral delivery system for treatment of respiratory diseases

 





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.”

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Wednesday, June 19, 2024

PLGA-PEG-NH2 from PolySciTech used in development of cerebrospinal-protein corona-covered nanoparticles to study neural cell interactions

 



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”


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Friday, June 14, 2024

mPEG-PLGA from PolySciTech used in development of polymeric nanoparticles combination therapy.

 



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.”

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Thursday, May 30, 2024

PLGA-Rhodamine used in development of micropatches for immunotherapy of cancer.

 

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”

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