Self-assembled supramolecular thermoreversible β-cyclodextrin/ethylene glycol injectable hydrogels with difunctional Pluronic®127 as controlled delivery depot of curcumin. Development, characterization and in vitro evaluation

Abstract

This study aimed to design a novel thermoreversible compact self-assembled host macromolecule based on β-cyclodextrin and low molecular weight ethylene glycol with a difunctional guest molecule i.e. poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) tri-block co-polymer (Pluronic® 127) through host-guest inclusion complexation in aqueous media using cold method. The injectable thermoreversible self-assembled supramolecular hydrogel was developed to encapsulate hydrophobic curcumin as anti-malignant agent and for controlled delivery to systemic circulation after in vivo application through subcutaneous route. As reversible supramolecular assembly, the thermoresponsive gels showed a unique structure-related reversible gel to sol transition above and below LCST determined via tube titling method. The rheological measurements of the supramolecular hydrogels showed a viscoelastic structure. Optical transmittance of supramolecular assembly also confirmed the thermoreversible sol–gel transitions. The strong potential of supramolecular assembly as injectable controlled delivery was assessed using curcumin as model active pharmaceutical ingredient for in vitro release experiments. The release experiments conducted in various dissolution medias and at different temperature programs showed maximum curcumin release in phosphate buffer solution (7.4) at 35 °C. methyl thiazolyl tetrazolium assay was used to assess the safety and efficacy of self-assembled supramolecular injectable hydrogels. In vitro cytotoxicity study showed that blank supramolecular gels are non-toxic to the L929 cells. While curcumin released from supramolecular injectable hydrogels (Cur-β-CD/EG-PF127) has the ability to show pharmacological activity and kill the cancer cells. Furthermore the formation of channel type inclusion complex was studied through Fourier transformed infra-red spectroscopy, X-ray diffraction, thermogravimetric analysis, differential scanning calorimetric and scanning electron microscopic analysis.