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

作者全名：Huang, Hanmei; Shen, Yingyan; Yang, Xiaohong; Hou, Chao; Ke, Xiumei; Yang, Rongping

作者地址：[Huang, Hanmei; Yang, Xiaohong; Yang, Rongping] Southwest Univ, Chongqing Key Lab Chinese Med New Drug Screening, Chongqing, Peoples R China; [Shen, Yingyan] Chengdu Univ Tradit Chinese Med, Key Lab Breeding Base Systemat Res & Utilizat Chin, Med Resources Cofounded Sichuan Prov, Chengdu, Peoples R China; [Shen, Yingyan] Chengdu Univ Tradit Chinese Med, Minist Sci & Technol, Chengdu, Peoples R China; [Hou, Chao] Shaanxi Univ Chinese Med, Xianyang, Shaanxi, Peoples R China; [Ke, Xiumei] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China

通信作者：Ke, XM (通讯作者)，Chongqing Med Univ, Chongqing 400016, Peoples R China.; Yang, RP (通讯作者)，Southwest Univ, 2 Tiansheng Rd, Chongqing 400715, Peoples R China.

来源：JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001253689100001

JCR分区：Q1

影响因子：4.5

年份：2024

卷号：98

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Asiaticoside; Panax Notoginseng saponins; Nanocrystals; Dissolvable microneedles; Human skin fibroblasts; Hypertrophic scars

摘要：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 mu g and skin retention of 80.61 +/- 48.46 mu g were significantly higher than those of AS-PNS-NCs- Gels (134.84 +/- 27.66 mu g and 5.23 +/- 1.86 mu g, 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 mu g/patch) reduced the collagen volume fraction (CVF) and improved the collagen fiber arrangement by inhibiting the overexpression of transforming growth factor-81 (TGF-81) and a-Smooth muscle actin (a-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.

基金机构：Chongqing Municipal Education Commission for Science and Technology Research [KJZD-K202202801]

基金资助正文：This research was funded by the Chongqing Municipal Education Commission for Science and Technology Research (KJZD-K202202801) . The authors acknowledge the above sponsor.