Injectable and thermosensitive supramolecular hydrogels by inclusion complexation between binary-drug loaded micelles and α-cyclodextrin

Abstract

The combination of drug loaded micelles and hydrogel could overcome the limitations with the use of the individual components as drug carriers. Herein, novel injectable supramolecular hydrogels based on the inclusion complexation between α-cyclodextrin and the binary-drug loaded micelles which self-assembled from 8arm-polyethylene glycol-betulinic acid (BA)/hydroxycamptothecin (HCPT) were first prepared in aqueous media. As the reversible supramolecular assembly behavior, the thermosensitive hydrogels showed distinctive structure-related reversible gel-sol transition properties at a particular temperature. The gel-sol transition temperature was determined by the length of the PEG chains and the mass ratio between the binary-drug loaded micelles and α-cyclodextrin. In addition, the BA/HCPT-loaded hydrogel showed more effectively than that of free drugs and BA/HCPT-loaded micelles for in vitro and in vivo studies. Hence, such an injectable micellar hydrogel with a distinctive structure and thermosensitive would be a highly potential candidate for many intelligent delivery applications.

Keywords: Betulinic acid; Drug delivery; Hydrogel; Micelles; Polyethylene glycol.