Evaluation of various block copolymers for micelle formation and brain drug delivery: In vitro characterization and cellular uptake studies

摘要

The treatment of brain associated diseases is limited due to rapid drug release into blood circulation after administration of conventional dosage forms and the blood-brain barrier. Polymeric micelles have opened up new horizons for improving the drug delivery to brain particularly due to their small size, long circulation time, good stability and targetability. This study aims to evaluate the micelle forming ability of copolymers with varying block compositions and investigate their potential for brain drug delivery. Block copolymers from poly(styrene)-poly(acrylic acid) (PS-PAA), poly(ethylene glycol)-b-poly(lactic acid) (PEG-PLA) and distearyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE) groups were evaluated. The critical micelle concentration and crystallinity of the copolymers were determined. Furthermore, size, surface charge and morphologic structure of the micelles were characterized by dynamic light scattering and transmission electron microscopy. The cytotoxicity and cellular uptake of micelles were assessed on mouse brain endothelial (bEnd-3) cells. The results demonstrated the effectiveness of chemical composition and block lengths of copolymers on micelle formation and their interaction with bEnd-3 cells. Although micellization was observed for all block copolymers, polymeric micelles derived from PEG(5000)-PLA(4500) were found to be worthy for further consideration as pharmaceutical carriers which could improve brain uptake and efficacy of hydrophobic drugs that they carry. (C) 2016 Elsevier B.V. All rights reserved.