HRP-Loaded Bioresorbable Microspheres: Effect of Copolymer Composition and Molecular Weight on Microstructure and Release Profile

Abstract

Poly(DL-lactic-co-glycolic acid) microspheres are prepared using a double-emulsion technique and are loaded with the model enzyme horseradish peroxidase (HRP). These microspheres can be used alone or as coatings for bioresorbable fibers that may be used as scaffolds for tissue regeneration applications. The present study focuses on the effect of the copolymer's composition and initial molecular weight on the microsphere structure, encapsulation efficiency, and cumulative protein release for 12 weeks. The release profiles generally exhibits an initial burst effect accompanied by slow release over an extended period of time, during which diffusion rather than degradation controlled HRP release from these structures. An increase in the initial molecular weight or in the copolymer's lactic acid content results in larger microspheres with smoother surfaces, and a decrease in the burst release and in the total HRP release. Molecular weight is found to have a stronger effect than copolymer composition. We demonstrate that it is possible to obtain versatile release profiles, which can be tailored for specific applications by choosing the right initial molecular weight and copolymer composition.

Solid/Hollow Depots for Drug Delivery, Part 1: Effect of Drug Characteristics and Polymer Molecular Weight on the Phase-Inversion Dynamics, Depot Morphology, and Drug Release

“…For microspheres drug delivery systems, the MW of the polymer is an important parameter of the drug release. The drug release from high‐MW microspheres is usually slower than that from low MW microspheres . In injectable in situ depot‐forming systems, polymer MW is also expected to be an important factor on the release, so the drug release from two different MW polymers was compared.…”

PLGA Spherical Nucleic Acids

“…RG 502 has markedly higher release at each time interval and a faster release rate at early time points ( Figure ). This is likely because these particles consist of a polymer with a smaller molecular weight that results in faster release rate . Mechanistically, drug release from the PLGA NPs is a complicated process involving diffusion, hydrolysis, bulk erosion, and surface erosion, giving rise to different degradation and release rates achieved by changing the end group or molecular weight of the PLGA.…”

Cannabinoid derivate-loaded PLGA nanocarriers for oral administration: formulation, characterization, and cytotoxicity studies

“…32 On the other hand, low molecular weight and low lactide content result in a less hydrophobic polymer with increased rates of water absorption, hydrolysis, and erosion. Lactic acid is more hydrophobic than glycolic acid and, therefore, the PLGA copolymer becomes more hydrophobic with increase in its lactic acid content: 34 Drug release can be obviously affected by hydrophobic interactions between the drug and the polymer. The interactions between drugs and PLGA delivery systems and their impact on release profiles have been widely discussed previously.…”