Sustained drug release using supramolecular hydrogels composed of cyclodextrin inclusion complexes with PCL/PEG multiple block copolymers

Abstract

Methadone hydrochloride is a narcotic drug used to relieve chronic pain and control withdrawal symptoms in people undergoing detoxification for opiate addiction, but poses some limits. To reduce the limits and increase the drug’s effectiveness, supramolecular hydrogels composed of α-CD (α-cyclodextrin) and PCL/PEG (polycaprolactone/polyethylene glycol) copolymers, which gained attention due to their advantages, were chosen in this study as controlled-release formulations. PCL/PEG/PCL and PCL/PEG copolymers were synthesized by a microwave-assisted method and then supramolecular hydrogels were prepared by mixing the solutions of copolymers/drug and α-CD to make a methadone hydrochloride sustained-release system. Effects of the drug, copolymer, and α-CD concentrations and copolymer structure on gelation time were also investigated. The systems had rheological properties that depended on copolymer construction and component concentrations. The microwave-assisted method provides an accelerated synthesis of the copolymers with yield of 57 % and low level of impurities. The supramolecular hydrogels demonstrated shear thinning and thixotropic behavior and regained their networks quickly after passing through a fine needle. Due to the porous construction of supramolecular hydrogels, they swell in the presence of fluids and absorb large quantities of water, thereby making the system comprehensively biocompatible. In this study, supramolecular hydrogels composed of α-CD with tri- and di-block copolymers were investigated and found to have rheological properties that depended on copolymer construction and component concentrations. Changing one parameter alone like copolymer or α-CD concentration or the length of blocks could not significantly affect on the drug release, but combination of these factors was efficient. Results of the present study indicated that supramolecular hydrogels composed of α-CD and PCL/PEG copolymers are appropriate drug delivery systems that can release methadone hydrochloride in a sustained manner.