HYDROGEL MICRONEEDLE PATCH OF METFORMIN FOR DIABETIC WOUND HEALING

Desh Deepak, Arkendu Chatterjee, Mahesh Kumar Gupta, Prince*

ABSTRACT

Background: Chronic diabetic wounds heal slowly because of persistent inflammation, impaired angiogenesis, oxidative stress and bacterial burden. Metformin, a first-line antidiabetic drug, activates AMP-activated protein kinase (AMPK) and shows local pro-healing effects, but oral dosing delivers little drug to the wound bed and topical creams penetrate poorly through slough and the stratum corneum. Aim: To develop and evaluate a hydrogel microneedle (HMN) patch that delivers metformin hydrochloride locally into diabetic wounds in a sustained manner. Methods: Microneedle arrays (10 x 10, 600 µm height) were cast in polydimethylsiloxane (PDMS) molds from a blend of polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and sodium alginate, crosslinked with calcium ions and freeze-thaw cycling. Formulations were optimized using a 3² factorial design. The patch was characterized for morphology, mechanical strength, skin insertion, swelling, drug loading, in vitro release, ex vivo permeation, cytocompatibility, antibacterial activity and in vivo healing in streptozotocin-induced diabetic rats. Results: The optimized patch (MET-HMN) had sharp, uniform needles with a fracture force of 0.62 N per needle and over 95% insertion efficiency in porcine skin. It loaded 1.8 ± 0.1 mg metformin per patch and released 82% of the drug over 48 h following a Fickian diffusion profile. The patch was cytocompatible with fibroblasts (viability above 90%) and haemocompatible (haemolysis below 2%). In diabetic rats, MET-HMN closed 96% of the wound by day 14, against 68% for untreated controls and 81% for metformin gel, with better re-epithelialization, collagen deposition and vascularization. Conclusion: The metformin-loaded hydrogel microneedle patch is a promising, minimally invasive and sustained-release platform for diabetic wound care and merits further preclinical development.

Keywords: Metformin; Hydrogel Microneedles; Diabetic Wound Healing; Transdermal Delivery; Sustained Release; AMPK.