Injectable micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs

In this paper, an injectable micellar supramolecular hydrogel composed of alpha-cyclodextrin (alpha-CD) and monomethoxy poly(ethylene glycol)-b-poly(epsilon-caplactone) (MPEG(5000)-PCL5000) micelles was developed by a simple method for hydrophobic anticancer drug delivery. By mixing alpha-CD aqueous solution and MPEG(5000)-PCL5000 micelles, an injectable micellar supramolecular hydrogel could be formed under mild condition due to the inclusion complexation between alpha-CD and MPEG segment of MPEG(5000)-PCL5000 micelles. The resultant supramolecular hydrogel was thereafter characterized by X-ray diffraction (XRD) and Scanning electron microscopy (SEM). The effect of alpha-CD amount on the gelation time, mechanical strength and thixotropic property was studied by a rheometer. Payload of hydrophobic paclitaxel (PTX) to supramolecular hydrogel was achieved by encapsulation of PTX into MPEG(5000)-PCL5000 micelles prior mixing with alpha-CD aqueous solution. In vitro release study showed that the release behavior of PTX from hydrogel could be modulated by change the alpha-CD amount in hydrogel. Furthermore, such supramolecular hydrogel could enhance the biological activity of encapsulated PTX compared to free PTX, as indicated by in vitro cytotoxicity assay. All these results indicated that the developed micellar supramolecular hydrogel might be a promising injectable drug delivery system for anticancer therapy.