Introduction: Diabetic wounds are a challenge due to the resistance to healing caused by hyperglycemia, poor angiogenesis, and decreased expression of growth factors. Topical insulin therapy has been found to be beneficial in promoting the closure of the wound by increasing cell proliferation and collagen synthesis. However, the conventional insulin formulation has limitations such as rapid degradation, poor skin permeability, and short retention time. This study proposes a novel insulin-loaded transferosomal organogel formulation to improve transdermal delivery and sustained release for effective diabetic wound treatment. Objective: The objective of this study was to develop a transferosomal organogel formulation for sustained insulin release in diabetic conditions. Method: Insulin-loaded transferosomes were prepared by thin film hydration with soy lecithin and Span 80, followed by sonication. Eight different formulations (F1-F8) were tested for vesicle size, PDI, zeta potential, and entrapment efficiency (EE%). The best formulation (F3) was then mixed with a 2% HPMC-based organogel. Various physicochemical properties, drug content, rheology, pH, spreadability, gelation properties, in vitro drug release (Franz diffusion cell), and short-term stability were evaluated. Results: The optimized formulation F3 had optimal properties, which included vesicle size of 255 nm, PDI of 0.343, zeta potential of -34.5 mV, and EE% of 83.01 ± 1.5%. Transmission Electron Microscopy (TEM) images revealed spherical and evenly distributed vesicles measuring 110-170 nm. Transferosomes showed sustained release of insulin (90.56% at 24 h) compared to free insulin (99% at 6 h), following first-order kinetics (R² = 0.989) with Higuchi diffusion. The organogel was transparent, homogeneous, skin-compatible (pH 6.32 ± 0.02), and had appropriate viscosity (2500 ± 25 cps), with good spreadability and gelation at 31.9°C. Sustained release was observed up to 48 h (70.25%), and the formulation was stable for 1 month without any changes. Discussion: The optimized F3 transferosomes had optimal nanometric size and negative zeta potential, which provided electrostatic stability and biocompatibility for topical application. The high EE% value indicated effective encapsulation of insulin, while the sustained release profile, which was dominated by first-order kinetics and matrix diffusion, outperformed free insulin, thus reducing the need for frequent administration and systemic toxicity. The formulation, when incorporated into a hydroxypropyl methylcellulose (HPMC) organogel, improved thermosensitive gelation and spreadability, thus making it easy to conform to the wound surface. These properties are collectively beneficial for enhancing insulin bioavailability at the wound surface, thus having the potential to induce re-epithelialization and granulation tissue formation in diabetic models. Short-term stability confirms the manufacturability of the formulation; however, longterm stability and in vivo efficacy testing are required. Conclusion: The insulin-loaded transferosomal organogel had optimal stability, sustained release of insulin, and optimal physicochemical properties for topical application. This system, which enhances skin penetration and prolongs insulin bioavailability, has the potential to be a promising therapeutic approach for improving healing in diabetic wounds.
Bhakuni et al. (Tue,) studied this question.