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

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.

Micro and nanoscale characterization of poly(DL-lactic-co-glycolic acid) films subjected to the L929 cells and the cyclic mechanical load.

In this paper, the effect of the presence of L929 fibroblast cells and a cyclic load application on the kinetics of the degradation of amorphous PLGA films was examined. Complex micro and nano morphological, mechanical and physico-chemical studies were performed to assess the degradation of the tested material. For this purpose, molecular weight, glass transition temperature, specimen morphology (SEM, µCT) and topography (AFM) as well as the stiffness of the material were measured. The study showed that the presence of living cells along with a mechanical load accelerates the PLGA degradation in comparison to the degradation occurring in acellular media: PBS and DMEM. The drop in molecular weight observed was accompanied by a distinct increase in the tensile modulus and surface roughness, especially in the case of the film degradation in the presence of cells. The suspected cause of the rise in stiffness during the degradation of PLGA films is a reduction in the molecular mobility of the distinctive superficial layer resulting from severe structural changes caused by the surface degradation. In conclusion, all the micro and nanoscale properties of amorphous PLGA considered in the study are sensitive to the presence of L929 cells, as well as to a cyclic load applied during the degradation process.