Influence of end groups on in vitro release and biological activity of lysozyme from a phase-sensitive smart polymer-based in situ gel forming controlled release drug delivery system.

摘要

Phase-sensitive in situ gel forming controlled release formulations of lysozyme were prepared using poly lactic acid (PLA) and/or poly glycolic acid (PGA) based polymers differing in end groups in addition to composition, and a solvent system consisting of various ratios of benzyl benzoate (BB) and benzyl alcohol (BA). The amount of lysozyme in the released samples was determined by measuring absorbance at 280nm using suitable controls to nullify the effect of absorption of formulation degradation products. Biological activity of lysozyme was studied by an enzyme activity assay using Micrococcus lysodeikticus as substrate. Polymers bearing carboxylic acid end group were not soluble in 100% BB but polymers having ester end groups were soluble up to 27% (w/v) except polymer 4. A biphasic release profile consisting of slower first phase followed by faster second phase was observed. Formulations prepared from polymer with carboxylic acid groups showed significantly (p<0.05) lower burst release (4%) than those containing ester end groups (20-30%). However, formulations consisting of polymer with carboxylic acid end groups showed significantly (p<0.05) faster release rate of incorporated lysozyme, although the total amount released was less in comparison to the total amount released from formulations prepared using polymers containing ester end groups. The mean percentage specific enzyme activity (MPSEA) data were supported by the release profiles. In conclusion, polymer end groups may influence the release profiles of a protein from an in situ gel depot forming controlled release formulations.