Double Hydroxyl Salt as Smart Biocompatible pH-Responsive Carrier for 6-Mercaptopurine

Cancers (Basel). 2023 Nov 30;15(23):5670. doi: 10.3390/cancers15235670.

Abstract

Hydroxy double salts are layered materials that are considered to be biocompatible. For this reason, research has been initiated on the possibility of their use in drug delivery. Despite their use for several types of drugs, their potential for controlled release of mercaptopurine (MERC) has not been studied. In this work, the synthesized hydroxy double salt (HDS) material was used as a carrier for this drug for the first time. The effectiveness of HDS synthesis has been proven by such techniques as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Based on the FT-IR and energy-dispersive X-ray spectroscopy (EDS) results, the effectiveness of drug sorption was proven. The exact amount of drug retained was determined by the UV-Vis technique. The obtained results indicate that the drug is evenly distributed on the surface of the carrier, which is important during the controlled delivery of drugs. In the most important stage of the research, the effectiveness of drug release in response to changes in the pH of the environment was proven. The drug is not released into an environment that mimics healthy human tissues. It is released only after contact with the acidic environment that usually surrounds cancer cells. The low cellular toxicity of HDS and significant cytotoxic effect of HDS-MERC were confirmed by in vitro studies on MCF-7 human breast and DU145 prostate cancer cell lines and non-cancerous keratinocytes HaCaT. Interestingly, coupling with the HDS carrier increased the cytotoxic effect of MERC towards DU145 cells. Such an "intelligent" drug carrier for mercaptopurine has not been previously described in the literature. The obtained results indicate its great potential.

Keywords: 6-mercaptopurine; HDS; controlled release; pH-responsive carrier.