Novel controlled drug release system engineered with inclusion complexes based on carboxylic graphene

Abstract

A novel drug carrier is constructed by compositing hydrophilic hydroxypropyl-β-cyclodextrins (HP-β-CD) and carboxylated graphene nanomaterial (GO-COOH). Fourier transform infrared spectroscopy confirms that the two materials are successfully combined via chemical bonds. Further, a crosslinking agent of glutaraldehyde is applied to fabricate composite GO-COO-HP-β-CD nanospheres, as demonstrated by an atomic force microscope. Dexamethasone (DEX) is selected as the model drug, and the drug loading efficiency and water solubility of the nanospheres greatly increased. Additionally, the achieved DEX/nanosphere inclusion complex exhibits better heat resistance compared with pure DEX, which is a desired property for drug processing. More importantly, different models are applied to different releasing durations to investigate in detail the release profile of DEX. The best fitting release kinetics model is given to reveal the release mechanism of the drug delivery system. The highest hemolysis rate of the DEX/nanosphere inclusion is 0.44%, far lower than the standard of 5% delivered by the American Society for Testing and Materials, ensuring its safety in practical applications. Meanwhile, recalcification tests indicate that DEX/nanosphere retains the normal blood coagulation function. In vitro cytotoxicity tests of the inclusion demonstrate that the nanospheres have no toxicity and are qualified for intravenous applications with good blood compatibility. Finally, the bioactivity of DEX after release from the carriers is investigated. Results corroborate that the drug anti-inflammation efficacy is not affected and that the biomedical function can be well retained. The engineered controlled drug release system represents a promising formulation platform for a broad range of therapeutic medicine in pharmaceutical technology.