Co-assembly of block copolymers as a tool for developing novel micellar carriers of insulin for controlled drug delivery

摘要

In this study the co-assembly of two amphiphilic block copolymers with tailored composition and molecular characteristics, poly(ethylene oxide)-poly(epsilon-caprolactone)-b-poly(ethylene oxide) (PEO113-b-PCL35-b-PEO113) and poly(2-(dimethylamino)ethyl methacrylate)-b-poly(epsilon-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA(20)-b-PCL70-b-PDMAEMA(20)), was employed for preparation of a novel micellar system for controlled delivery of insulin. Mixed block copolymer micelles (MBCMs) of three different compositions were prepared by blending the two copolymers at molar ratios of 7:3, 1:1 and 3:7. Next, the electrostatic complexation between insulin and MBCMs with a focus on particle size, morphology, zeta potential and colloid stability as a function of insulin concentration in the aqueous solution was investigated by dynamic and electrophoretic light scattering as well as atomic force microscopy. The properties of systems were proven to depend on MBCMs composition and protein concentration. In vitro cytotoxicity of blank and insulin-loaded carriers was assessed by standard MIT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test. The release profile of insulin from selected carriers in phosphate buffer (pH 7.4) was also studied.