PLGA-Amine from PolySciTech used in development of nanoparticle targeting system for heart therapy.

 

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.”



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