Architecture based selectivity of Amphiphilic block copolymers of poly(ethylene oxide) and poly(ε-caprolactone) for drug delivery

Abstract

Architecture of amphiphilic block copolymers is an important parameter that affects their critical micelles concentration (CMC), drug loading capacity and drug release behavior. In this context, 4-arm star-shaped block copolymers comprising of poly(ethylene oxide) as a hydrophilic segment and poly(ε-caprolactone) as a hydrophobic part, 4 s-P(CL-b-EO), is compared with its linear counterpart having otherwise similar total molar mass, chemical composition and molar mass of individual components (PCL-b-PEO-b-PCL). As a first step, the micelles prepared by linear block copolymer (LPM) and star-shaped block copolymer (SPM) were compared for CMC, drug encapsulation capacity, and drug release behavior. Micelles based on star-shaped polymers were found to have low CMC, high drug encapsulation capacity and better sustained release behavior. Blood hemolysis and cytotoxicity studies of both linear and star-shaped block copolymers revealed that these are safer to use for biological applications. Micelles based on star shaped polymers (SPM) and linear block copolymer (LPM) were further employed for individual delivery of cefixime (CEF) and its co-delivery with clarithromycin (CLA). Finally, growth inhibition efficiency of SPM, LPM, CEF, CLA, CEF-SPM, CEF-LPM, CEF-CLA-SPM, and CEF-CLA-LPM are evaluated against S. pneumoniae and S. pneumoniae (resistant) by antibacterial assay and morphological topography imaging by AFM. Minimum inhibitory concentration (MIC50) of drugs encapsulated in SPM is found to be considerably lower compared to direct application of drugs and drug encapsulated in LPM.