PLGA from PolySciTech used in development of nanoparticle delivery system for treatment of congenital lysosomal disorders

Alterations in normal lysosomal function due to genetic disorders can lead to potentially lethal conditions. Researchers at Barcelona Institute for Science and Technology, University of Barcelona, University of Maryland, Autonomous University of Barcelona, and Institution of Catalonia for Research and Advanced Studies (Spain) used PLGA (AP083 and AP201) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles with controlled LA:GA ratio to study release of enzymes and behavior of the particles under lysosomal conditions. This research holds promise to provide for treatment of lysosomal and other disorders. Read more: del Moral, Maria, Maximilian Loeck, Eameema Muntimadugu, Guillem Vives, Vy Pham, Peter Pfeifer, Giuseppe Battaglia, and Silvia Muro. "Role of the Lactide: Glycolide Ratio in PLGA Nanoparticle Stability and Release under Lysosomal Conditions for Enzyme Replacement Therapy of Lysosomal Storage Disorders." Journal of Functional Biomaterials 14, no. 9 (2023): 440. https://www.mdpi.com/2079-4983/14/9/440

“Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤?35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (<1 week) because of their smaller diameter, and 75:25 NPs did not destabilize in 4 weeks. All formulations presented burst release under lysosomal conditions (56–78% of the original load within 30 min), with 50:50 and 60:40 NPs releasing an additional small fraction after week 1. This provided 4 weeks of sustained catalytic activity, sufficient to fully degrade a substrate. Altogether, the 60:40 NP formulation is preferred given its higher EE, and 50:50 NPs represent a valid alternative, while the highest stability of 75:25 NPs may impair lysosomes. These results can guide future studies aiming to translate PLGA NP-based ERT for this and other LSDs. Keywords: lysosomal storage disorder; enzyme replacement therapy; hyaluronidase; poly(lactide-co-glycolide) nanoparticles; copolymer ratio; nanoparticle stability; enzyme release”