Design and evaluation of Phospholipon® 90H nanoparticle-loaded composite gel for enhanced wound healing

Abstract

Lipid-based drug delivery carriers have exhibited substantial potential for promoting wound healing. Here, Phospholipon® 90H (P90H) based lipid nanoparticles (LNPs) encapsulating Capparis spinosa seed oil (CSO) and clove oil (CO) were developed by solvent emulsification method followed by probe sonication. Later, LNPs were incorporated in the composite gel (GP1 to GP5) with or without ofloxacin (OFX). Therapeutic oils were initially evaluated by scratch assay, antibacterial activity, MTT assays and antioxidant activity to evaluate their potential for wound healing. Lipid nanoparticles were characterized through particle size, zeta potential, polydispersity index, FTIR, SEM, and gels matrix was evaluated for viscosity, pH, spreadability, drug content and OFX release.

CSO and CO demonstrated enhanced wound healing in scratch assays by promoting Hep-G2 cell migration, exhibited dose-dependent antibacterial activity against S. aureus and E. coli, showed notable antioxidant potential via DPPH scavenging, and maintained high cell viability at lower concentrations in MTT assays, thus indicating their potential for wound healing. The prepared lipid carriers exhibited particle sizes between 91.64 and 134.2 nm with a PDI below 0.5, indicating uniform particle distribution. The developed hydrogels demonstrated optimum viscosity, pH and spreadability for effective topical use. Optimized gel (GP5) formulation depicted a controlled OFX release at pH 7.4, with cumulative release reaching 36.59 ± 1.27% at 2 hours, 84.37 ± 7.55% at 8 hours, and released maximum contents up to 24 hours.

During in vivo studies, the GP5 composite gel showed significant wound healing efficacy, achieving up to 76% wound contraction by day 6 and complete closure by day 12. Immune assay revealed that GP5 modulated key wound healing biomarkers, indicating enhanced anti-inflammatory, angiogenic and apoptotic responses conducive for tissue repair. Histopathological evaluation confirmed that GP5-treated wounds exhibited enhanced healing, characterized by well-formed epithelium, reduced macrophage infiltration, and the presence of defined hair follicles and connective tissue. In conclusion, GP5 showed tremendous potential for accelerating the healing of open wounds.

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Materials

Phospholipon® 90H was gifted by Lipoid. Ofloxacin was received as gift sample by Saffron Pharmaceuticals Faisalabad, Pakistan. Clove oil was obtained from Go Natural Pakistan. Capparis spinosa seed was purchased from the local market and oil was extracted via cold pressing. Kolliphor® P 188, Carbopol 940® and sodium hydroxide were acquired from Sigma Aldrich. Triethylamine was purchased from Uni-chem. Tween® 80, methanol, monobasic potassium phosphate were purchased from Daejung Company Korea

Muhammad Asim, Ikram Ullah khan, Syed Haroon Khalid, Sajid Asghar, Design and evaluation of Phospholipon® 90H nanoparticle-loaded composite gel for enhanced wound healing, Journal of Drug Delivery Science and Technology, 2025, 107906, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.107906.