Topical astragaloside IV-releasing hydrogel improves healing of skin wounds in vivo.
ABSTRACT Topical delivery of therapeutic agents at the time of injury to accelerate skin repair and prevent the formation of scars during the wound healing process has received increasing attention and represents a novel regenerative and prophylactic strategy for wound treatment. The aim of this study was to invesigate, for the first time, the influence of topical astragaloside IV-releasing hydrogel on the wound repair and regeneration. Using the sodium alginate-gelatin as a hydrogel vehicle, the astragaloside IV was incorporated into the topical carrier and kept releasing with a sustained manner at the wound site. With the rat skin excision model, regulation of the astragaloside IV hydrogel on the wound repair and regeneration were investigated. It was found that the astragaloside IV hydrogel was effective in the skin wound repair, leading to a significant improvement on the wound closure, collagen synthesis and skin tensile strength recovery. Meanwhile, for the first time, that functions of astragaloside IV hydrogel in activating the skin appendages regeneration and increasing the transforming growth factor-β(1) (TGF-β(1)) level in serum were shown. Results of this study provided evidence for the alginate-gelatin hydrogel as efficient carrier for the topical delivery of bioactive molecules to the injured site. The astragaloside IV releasing hydrogel was shown a promising therapeutic formulation for wound healing, as well as its regenerative feature and underlying mechanism contribute to the skin regeneration were disclaimed.
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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 (-23.6mV±1.5mV), 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.International journal of pharmaceutics 03/2013; · 2.96 Impact Factor