In situ gelling alginate/sodium montmorillonite/castor oil nanoemulsion composite film: A multifunctional antiviral, anti-inflammatory and hemostatic platform for HSV-1-infected wound applications

Abstract

A novel alginate (ALG)-based in situ, gel-forming, film-forming ternary composite incorporating sodium montmorillonite (Na+MMT) and a castor oil (CO) nanoemulsion was developed as a multifunctional platform for the topical treatment of Herpes Simplex Virus type 1 (HSV-1) lesions. The dry composite film exhibited a porous, sponge-like morphology with an average pore size of ∼5 μm and a hydrophilic surface (contact angle: 58.3 ± 2.4°), enabling rapid hydration and conversion into a hydrogel within 30 ± 5 s upon contact with aqueous media. ATR-FTIR and XRD analyses confirmed intercalation of the CO nanoemulsion within Na+MMT layers and clay exfoliation, evidenced by the disappearance of the basal reflection at 2θ = 9.1°. The CO nanoemulsion had a mean droplet size of 220 ± 12 nm, a PDI of 0.28 ± 0.03, and a ζ-potential of −32.4 ± 1.6 mV+.The hydrated composite demonstrated a high swelling capacity (420 ± 18%) and viscoelastic behavior, with a storage modulus (G′) of 3.1 × 103 Pa at 33 °C. Mechanical testing revealed adequate flexibility and resilience (elongation at break: 4.9 ± 0.3%; puncture energy: 1.26 mJ/mm3). Thermal analysis indicated stability up to 180 °C, with a main decomposition event at 285 °C. In vitro, studies showed excellent biocompatibility (>95% cell viability) and hemocompatibility (hemolysis <2%). The composite film significantly inhibited HSV-1 replication in HaCaT cells (97.73 ± 0.81% I), whereas the Na+MMT/CO nanoconjugate achieved 99.99% inhibition without virucidal activity. Additionally, the film reduced TNF-α secretion by 47 ± 6% in LPS-stimulated macrophage–fibroblast co-cultures, confirming its anti-inflammatory potential.Overall, the ALG/Na+MMT/CO nanoemulsion composite film integrates antiviral, anti-inflammatory, hemostatic, and mucoadhesive properties, supporting its potential as a biocompatible topical dressing for HSV-1 lesions.