Synthesis and characterization of dual light/temperature-responsive supramolecular injectable hydrogel based on host-guest interaction between azobenzene and starch-grafted β-cyclodextrin: Melanoma therapy with paclitaxel

Abstract

Injectable stimuli-responsive hydrogels could offer an opportunity for local administration at the tumor site and a sustained drug release. In this paper, a copolymer of azobenzene derivative and N-isopropyl acrylamide (NIPAM) was synthesized, which are performed as light- and thermo-sensitive parts, respectively. The DAS@SCD/NIPAZO hydrogel was prepared upon the establishment of host-guest interactions between the hydrophobic core of CD and azobenzene moiety. The LCST of the synthesized copolymer was modified from 31.3 °C to 36.5 °C by the incorporation of the hydrophilic host moieties of the modified starch into the NIPAM copolymer structure. The LCST-based property of the hydrogel made it syringable in low temperatures and switch to a gel state after local injection. The drug release profile of the hydrogel was explored in four different conditions involving two distinct temperatures combined with two different light wavelengths to examine the light- and thermo-sensitivity of the hydrogel. Moreover, a Paclitaxel-loaded hydrogel was prepared to study the in vitro efficiency of the sample and was investigated by MTT assay against the cancerous fibroblastic cells (A-431), which revealed a sharp decline in cell viability under 365 nm light irradiation; furthermore, to evaluate the in vivo effects of the PTX-loaded hydrogel, histological studies based on staining techniques were carried out.