FORMULATION AND EVALUATION OF ETHOSOMAL GEL OF CARICA PAPAYA AND BRYOPHYLLUM PINNATUM LEAF EXTRACTS FOR THE EFFECTIVE MANAGEMENT OF WOUND HEALING

Abstract

Background: Plant-derived extracts are being investigated as potential sources of bioactive compounds for topical wound management. Ethosomes, composed of phospholipids and a relatively high proportion of ethanol, offer a vesicular delivery approach that may improve the transport of incorporated constituents across skin barriers. Objective: The present study aimed to formulate and evaluate an ethosomal gel containing Carica papaya and Bryophyllum pinnatum leaf extracts and investigate its physicochemical characteristics, release and permeation behavior, antimicrobial activity, preliminary irritation potential, and wound-healing efficacy. Methods: Ethosomes containing the two herbal extracts were prepared by the thin-film hydration method using lecithin concentrations of 1.0–2.0%, ethanol volumes of 10–20 mL, and a constant cholesterol concentration of 0.2%. The selected dispersion was incorporated into a Carbopol 980NF gel base at 0.75% w/w. Vesicle size, polydispersity index (PDI), zeta potential, morphology, and entrapment efficiency were evaluated. The gel was characterized for pH, extract content, spreadability, viscosity, In vitro release, ex vivo permeation through porcine skin, antimicrobial activity, and irritation potential using the hen's egg test–chorioallantoic membrane (HET-CAM) assay. Wound-healing activity was investigated using an excision-wound model in Wistar rats, with untreated wounds and Betadine ointment serving as comparators. Results: The optimized ethosomal dispersion exhibited a mean vesicle size of 189.3 ± 2.55 nm, a PDI of 0.6436 ± 0.03, a zeta potential of −21.79 ± 0.75 mV, and an entrapment efficiency of 84.23 ± 2.15%. The formulated gel had a pH of 6.8, extract contents of 90.95% for C. papaya and 88.65% for B. pinnatum, spreadability of 33.65 g·cm/s, and viscosity of 39,435 cP. At 24 h, cumulative In vitro release reached 91.26 ± 1.86% and 94.18 ± 1.93% for the respective extracts, while ex vivo permeation reached 63.28 ± 1.62% and 67.42 ± 1.71%. The gel produced inhibition zones of 18.6 ± 0.6 mm against Staphylococcus aureus and 16.8 ± 0.5 mm against Bacillus subtilis. Its HET-CAM irritation score was 0.38 ± 0.11. In the rat excision-wound model, the formulation produced 95.8 ± 2.0% wound contraction by day 15, compared with 82.8 ± 3.0% in untreated wounds and 97.2 ± 1.6% with Betadine ointment. The epithelialization period was 14.7 ± 0.6 days for the herbal ethosomal gel. Conclusion: The combined herbal ethosomal gel demonstrated favorable formulation characteristics, measurable antimicrobial activity, low acute irritation potential in the HET-CAM assay, and enhanced wound closure in the experimental model. These findings support further investigation of the formulation, including standardized phytochemical characterization, statistical validation, dermal safety assessment, and controlled efficacy studies.