Release optimization of epidermal growth factor from PLGA microparticles

Abstract

The objective of this study was to prepare poly lactic-co-glycolic acid (PLGA)-based microparticles as potential carriers for recombinant human epidermal growth factor (rhEGF). In order to optimize characteristic parameters of protein-loaded microspheres, bovine serum albumin (BSA) was selected as the model protein. To reduce burst release as a common problem of microspheres, a proper alteration in the particle composition was used, such as addition of poly vinyl alcohol and changes in initial drug loading. The effects of these parameters on particle size, encapsulation efficiency and in vitro release kinetics of BSA in PLGA microspheres were investigated using a Box-Behnken response surface methodology. The biological activity of the released rhEGF was assessed using human skin fibroblasts cell proliferation assay. The prepared rhEGF-loaded microspheres had an average size of 6.44 ± 2.45 µm, encapsulation efficiency of 97.04 ± 1.13%, burst release of 13.06 ± 1.35% and cumulative release of 22.56 ± 2.41%. The proliferation of human skin fibroblast cells cultivated with rhEGF releasate of microspheres was similar to that of pure rhEGF, indicating the biological activity of released protein confirming the stability of rhEGF during microsphere preparation. These results are in agreement with the purpose of our study to prepare rhEGF-entrapped PLGA microparticles with optimized characteristics.

Controlled release of rhEGF and rhbFGF from electrospun scaffolds for skin regeneration

“…In our previous work, PLGA microspheres with the feature of controlled release and reduced burst release were produced via the W/O/W double emulsion technique and the process was optimized . The burst release of the proteins from PLGA microspheres depends on several factors which are relevant to the composition of the microspheres.…”

A reformative shear precipitation procedure for the fabrication of vancomycin-loaded poly(lactide-co-glycolide) microspheres

“…However, the observations from another study were inconsistent with our findings, where higher initial drug loading resulted in decreased encapsulation efficiency. 32 This was due to the possibility that the higher initial drug load produced a higher drug concentration in the emulsion droplets, which led to an increase in the concentration gradient of the drug from the emulsion droplets to the shear medium. This could act as a driving force for drug diffusion out of the polymer matrix, resulting in drug loss during formation of the microspheres.…”

Production methods and stabilization strategies for polymer-based nanoparticles and microparticles for parenteral delivery of peptides and proteins

“…Furthermore, the stable model proteins BSA and lysozyme have frequently been used instead of more labile and clinically relevant proteins. Authors who did use therapeutic proteins, in most cases, made another step by also performing in vitro or in vivo efficacy and/or toxicity studies with their formulations [52,60,61,71,84,85,91,94,96,[100][101][102][103][104], thereby generating more relevant information on the potential applicability in the clinic of the formulation developed.…”