Gelatin-based hydrogels with β-cyclodextrin as a dual functional component for enhanced drug loading and controlled release

In this paper, we demonstrate a simple and practical method to prepare chemically crosslinked gelatin-based hydrogels using beta-cyclodextrin (beta-CD) that plays a dual role as a crosslinker as well as a host molecule for enhanced binding of anticancer drug methotrexate (MTX), to achieve high drug loading level as well as controlled and sustained release of the anticancer drug. For this purpose, a series of novel beta-CD-crosslinked gelatin-based hydrogels were synthesized and characterized. The beta-CD content of the hydrogels was 11-15%, and the crosslinking degree was 21-36%. The gelatin-based hydrogels could swell well in PBS buffer. The hydrogels degraded hydrolytically and the degradation was accelerated by collagenase in PBS buffer. It was found that the higher water content resulted in faster biodegradation of the hydrogels regardless of the crosslinker used. Pyrene was used as a fluorescence probe to investigate the micro-environment of the gelatin-based hydrogels. Pyrene was well adsorbed in the beta-CD-crosslinked hydrogels, and the pyrene molecules in the hydrogels were included and complexed within the hydrophobic cavities of the beta-CD crosslinkers. The adsorption, loading, binding and complexation, and release of MTX in or from the hydrogels were investigated. MTX was adsorbed and loaded into the hydrogels by immersing the swollen hydrogel samples in MTX saturated aqueous solution. The loading of MTX in the hydrogels was confirmed by measuring the UV-vis spectra of the MTX-loaded hydrogels, the spectra indicated that the loaded MTX was complexed by beta-CD in the beta-CD-crosslinked hydrogels. Our data showed that the complexation of MTX with beta-CD crosslinkers largely increased the loading level of MTX in the hydrogels. The complexation could also reduce the initial burst release effect, and then retard the release of the complexed MTX for a certain period, until the hydrogels started to hydrolytically degrade and all remained MTX was released. Due to the unique structures and properties, the beta-CD-crosslinked gelatin-based hydrogels demonstrated an interesting multiphasic profile for controlled and sustained release of the MTX drug. Thus, the beta-CD-crosslinked gelatin-based hydrogels may be utilized as a promising drug carrier for controlled and sustained release and localized delivery of anticancer drugs.