Dissolvable microneedles loaded with asiaticoside nanocrystals stabilized by Panax Notoginseng saponins for hypertrophic scar treatment

Hypertrophic scars (HS) are fibroproliferative disorders caused by overgrowth of connective tissue during wound repair, for which effective treatment is lacking. Although Asiaticoside (AS) facilitates scarless wound healing, its low permeability through the skin and poor solubility in water pose major barriers to clinical application. Dissolvable microneedles (DMNs) have emerged as a potent transdermal drug delivery technique capable of penetrating the stratum corneum barrier. However, due to the lipid-soluble nature of AS, it is incompatible with water-soluble microneedle matrices. This incompatibility could result in an uneven dispersion of drugs, making the creation of DMNs loaded with AS challenging. In this study, a pharmacodynamic molecule called Panax Notoginseng Saponins (PNS), which similarly encourages scarless wound healing, was used as a stabilizer. Asiaticoside-Panax Notoginseng Saponin (AS-PNS-NCs) were prepared by solvent evaporation coupled with ultrasonication to improve the water solubility of AS. The average particle size was 158.70 ± 10.99 nm, Polydispersity index (PDI) was 0.18 ± 0.012, and Zeta potential was −15.5 ± 1.08 mV. A centrifugal filling technique was then used to create AS-PNS-NCs-DMNs. After 24 h of in vitro transdermal drug release, the cumulative transdermal release of AS-PNS-NCs-DMNs of 319.00 ± 50.01 μg and skin retention of 80.61 ± 48.46 μg were significantly higher than those of AS-PNS-NCs- Gels (134.84 ± 27.66 μg and 5.23 ± 1.86 μg, respectively). Furthermore, it was demonstrated that AS-PNS-NCs-DMNs may suppress human skin fibroblasts (HSF) in vitro migration rate and proliferative activity. In rabbit ear keloid model, AS-PNS-NCs-DMNs (containing AS 1536.49 ± 93.14 μg/patch) reduced the collagen volume fraction (CVF) and improved the collagen fiber arrangement by inhibiting the overexpression of transforming growth factor-β1 (TGF-β1) and α-Smooth muscle actin (α-SMA) at the scar site, resulting in a reduction of scar thickness. It is demonstrated that AS-PNS-NCs-DMNs can effectively inhibit scar proliferation.