Astragaloside IV-loaded nanoparticle-enriched hydrogel induces wound healing and anti-scar activity through topical delivery

Abstract

This study aims to investigate the novel preparation of solid lipid nanoparticle-enriched hydrogel (SLN-gel) for the topical delivery of astragaloside IV and to determine the effects of astragaloside IV-based SLN-gel on wound healing and anti-scar formation. Solid lipid nanoparticles (SLNs) were prepared through the solvent evaporation method. The particle size, polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), drug release, and morphological properties of the SLNs were characterized. The optimized SLNs were incorporated in carbomer hydrogel to form an SLN-enriched gel (SLN-gel) carrier. The effects of astragaloside IV-enriched SLNs on wound healing were determined using the wound scratch test, and their uptake by skin cells was tested in vitro. With the rat full-skin excision model, the in vivo regulation of astragaloside IV-based SLN-gel in the wound stages of re-epithelization, angiogenesis, and extracellular matrix remodeling was investigated. The best formulation of astragaloside IV-based SLNs had high EE (93% ± 5%) and ZP (-23.6 mV ± 1.5 mV), with a PDI of 0.18 ± 0.03 and a drug loading percentage of 9%. Astragaloside IV-based SLNs and SLN-gel could release drug sustainably. Astragaloside IV-based SLNs enhanced the migration and proliferation of keratinocytes and increased drug uptake on fibroblasts in vitro (P<0.01) through the caveolae endocytosis pathway, which was inhibited by methyl-β-cyclodextrin. Astragaloside IV-based SLN-gel strengthened wound healing and inhibited scar formation in vivo by increasing wound closure rate (P<0.05) and by contributing to angiogenesis and collagen regular organization. SLN-enriched gel is a promising topical drug delivery system. Astragaloside IV-loaded SLN-enriched gel was proven as an excellent topical preparation with wound healing and anti-scar effects.