Preparation and Evaluation of Zn2(BDC)2(DABCO)-β-CD MOF as a Dual-Drug Delivery Nanocomposite Containing Tetracycline and Indomethacin for Skin Wound Healing in BALB/c Mice.

BACKGROUND

Skin wounds complicated by infection and inflammation represent a major clinical challenge and require effective delivery systems that combine antimicrobial and anti-inflammatory agents to promote healing. Nanobased systems, such as metal-organic frameworks (MOFs), are promising platforms for dual-drug delivery because of their high porosity, tunable structure, and biocompatibility.

OBJECTIVES

This study aimed to synthesize a Zn2(BDC)2(DABCO)-β-cyclodextrin MOF nanocomposite using a hydrothermal method and to load indomethacin and tetracycline to develop a dual-drug delivery system that enhances the efficiency and therapeutic efficacy of topical treatment for skin wound healing.

METHODS

The morphology of the nanocomposite was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Zeta potential was measured using a Zetasizer; the crystalline structure was evaluated by X-ray diffraction (XRD); the physicochemical structure was assessed by Fourier transform infrared (FTIR) spectroscopy; and structural porosity before and after drug loading was analyzed by Brunauer-Emmett-Teller (BET) analysis. The system was then evaluated for in vitro cytotoxicity using the MTT assay, cytokine levels in blood samples from treated mice, and in vivo efficacy in mice, compared with the corresponding pure drugs.

RESULTS

The synthesized MOF exhibited high crystallinity. The average particle size was 277 nm for the blank nanocomposite and 545 nm for the drug-loaded nanocomposite, with a zeta potential of -2.6 mV. The drug-loading efficiency in phosphate-buffered saline (PBS; pH 7.4) was 28%, with biphasic release comprising an initial burst followed by sustained release over 144 hours. The BET surface area decreased after drug loading. In vitro studies showed that the drug-loaded nanocomposite was noncytotoxic to L929 fibroblast cells at all tested concentrations. The loaded MOF nanocomposite group showed significantly accelerated wound closure (97.5% on day 6) compared with all other groups (P < 0.05). Cytokine assays in mouse blood samples showed increased interleukin 10 (IL-10) and decreased interferon gamma (IFN-γ) in the group treated with the loaded nanocomposite compared with the control group.

CONCLUSIONS

The Zn2(BDC)2(DABCO)-β-CD nanocomposite containing tetracycline and indomethacin exhibited noncytotoxic behavior, enhanced wound-healing efficacy, and sustained drug release under physiological conditions. These findings highlight its potential as a promising topical drug delivery system.