Construction of micelles based on biocompatible pseudo-graft polymers via β-cyclodextrin/cholesterol interaction for protein delivery

Abstract

A novel pseudo-graft copolymer was developed for protein delivery, based on the self-assembly of (6-(2-aminoethyl)-amino-6-deoxy)-cyclodextrin (β-CDen)-modified poly(aspartic acid) (PASP-CD) with cholesterol-modified poly(D,L-lactide) (PLA-Chol) by host–guest inclusion complexation. The chemical structures of polymers were confirmed by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. These components were then investigated for their ability to form nanoparticles and encapsulate protein. The diameter of micelles in water ranged from 70 to 200 nm as determined by dynamic light scattering, and the micelles were spherical in shape as observed by transmission electron microscopy. A model protein, bovine serum albumin (BSA), was encapsulated into the pseudo-graft copolymer micelles. The encapsulation efficiency (EE) and loading capacity (LC) of BSA in the micelles could be well tuned by adjusting the composition of the pseudo-graft copolymers. The micelles with a lower molar ratio of CD and cholesterol (hydrophilic/hydrophobic) exhibited a higher EE and LC. While in vitro release studies showed that a shorter chain of hydrophobic segment and higher hydrophilic/hydrophobic molar ratio could enhance the release rate. Cell viability studies showed that these materials possessed good cell viability (>95%). These results suggest that the degradable copolymers with appropriate hydrophilic and hydrophobic composition are able to self-assemble into micelles that are an effective and biocompatible vehicle for delivering protein, paving a new way for the application of pseudo-graft copolymers in protein or peptide delivery.