Hydrogel film-forming spray formulation containing propolis-based nanostructured lipid carriers of α-mangostin for diabetic wound repair

Diabetic wounds are difficult to treat due to persistent inflammation, delayed tissue repair, and high susceptibility to infection. α-Mangostin (αM), a xanthone with strong anti-inflammatory and wound-healing properties, shows improved solubility and therapeutic performance when encapsulated in propolis-based nanostructured lipid carriers (Nanopropolis-αM). Incorporating these nanoparticles into a hydrogel film-forming spray (HFFS) offers uniform application and sustained delivery. This study aimed to formulate, characterize, and evaluate an αM-loaded propolis-based NLC HFFS (HFFS-Nanopropolis-αM). The spray was prepared using chitosan, Carbopol 940, and sodium carboxymethyl cellulose. Physicochemical evaluations included pH, viscosity, spray angle, weight uniformity, particle size, zeta potential, and entrapment efficiency. The optimized formulation also underwent TEM imaging, in vitro release testing, cytocompatibility assessment using the WST-8 assay in NIH-3T3 cells, and 14-day in vivo wound-healing studies in alloxan-induced diabetic mice. The optimal HFFS containing 0.1 % Carbopol 940 exhibited suitable pH (7.30 ± 0.01), viscosity (19.97 ± 2.12 mPa.s), spray angle (62.02 ± 3.83°), film formation time (113.000 ± 11.372 s), particle size (85.17 ± 2.55 nm), zeta potential (−13.90 ± 2.18 mV), and entrapment efficiency (91.31 ± 0.58 %). It showed good 28-day stability and followed Higuchi release kinetics (R² = 0.998). Cytocompatibility was acceptable at experimentally testable concentrations, and the viability value at the intended dose reflects a modeled estimate due to assay dilution limits. In vivo, HFFS-Nanopropolis-αM significantly accelerated wound closure (99.53 ± 1.04 %) compared with silver sulfadiazine (89.24 ± 3.04 %, p < 0.01), supported by improved histological regeneration. Overall, the formulation demonstrates strong promise for diabetic wound management. Each author listed above affirms that they have made a substantial contribution to this work in one or more of the following: conception or design of the work; - data acquisition, analysis, or interpretation; - drafting the manuscript or revising it critically for important intellectual content; - final approval of the version to be published; - accountability for all aspects of the work, ensuring integrity and accuracy. Each author also agrees that no one who qualifies for authorship has been excluded, and that all those who made lesser contributions are acknowledged appropriately. By signing below, the Corresponding Author confirms that all authors have read, understood, and agreed to the terms in this Authorship Agreement / Declaration, and signs this document on behalf of all listed co‑authors.