Investigating bevacizumab and its fragments sustained release from intravitreal administrated PLGA Microspheres: A modeling approach.

Eur J Pharm Biopharm

Faculty of Materials Science and Engineering, Warsaw University of Technology, ul. Wołoska 141, 02-507 Warsaw, Poland.

Published: December 2023

Intravitreal administrated bevacizumab has emerged as an effective antibody for suppressing VEGF expression in age-related macular degeneration (AMD) therapy. This study discusses certain issues related to the sustained release of bevacizumab from intravitreal poly(lactic-co-glycolic acid) (PLGA) microspheres. A computational model elucidating the ocular kinetics of bevacizumab is demonstrated, wherein the release of the drug from PLGA microspheres is modeled using the Koizumi approach, complemented by an empirical model that links the kinetics of bevacizumab release to a size-dependent hydrolytic degradation of the drug-loaded polymeric microparticles. The results of the simulation were then rigorously validated against experimental data. The as-developed model proved remarkably accurate in predicting the time-concentration profiles obtained following the intravitreal injection of PLGA microspheres of significantly different sizes. Notably, the time-concentration profiles of bevacizumab in distinct ocular tissues were almost unaffected by the size of the intravitreally administered PLGA microparticles. Furthermore, the model successfully predicted the retinal concentration of bevacizumab and its fragments (e.g., ranibizumab) administrated in the form of a solution. As such, this model for drug sustained release and ocular transport holds tremendous potential for facilitating the reliable evaluation of planned anti-VEGF therapies.

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Source
http://dx.doi.org/10.1016/j.ejpb.2023.11.015DOI Listing

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