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Archive > Volume 15 Issue 2 > 2023,15(2):251-262. DOI:https://doi.org/10.1016/j.chmed.2022.10.002 Prev Next

丹參酮IIA自溶微針的制備及其對人皮膚成纖維細胞增殖的抑制作用

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Preparation of tanshinone IIA self-soluble microneedles and its inhibition on proliferation of human skin fibroblasts

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    摘要:
    目的：增生性瘢痕 (HS) 是發(fā)生在人體皮膚上的多種皮膚組織纖維化疾病，迄今尚無有效的治療方法。丹參酮IIA (tanshinone IIA, TSA) 是著名藥用植物丹參 (Salvia miltiorrhiza) 的活性成分，具有抑制HS細胞增殖的作用。因此，本研究的目的是制備TSA自溶性微針，以增強其皮膚滯留性，突破HS部位表皮結(jié)締組織和角質(zhì)層明顯增厚的困難。利用人皮膚成纖維細胞 (HSF) 研究了其抑制HS的可能作用機制。 方法：采用負模鑄造法制備丹參酮IIA自溶微針 (TSA-MN)。采用Box-Behnken效應(yīng)面法對微針的處方工藝進行優(yōu)化。選擇不同介質(zhì)考察其透皮吸收和體外釋放能力。此外，采用細胞計數(shù)試劑盒-8 (Cell Counting Kit-8, CCK8) 法和Western blot法研究TSA-MN對HSF生物學(xué)特性的影響。 結(jié)果：TSA-MN體外釋放和透皮性能均優(yōu)于TSA和普通劑型，具有顯著的緩釋效果和皮膚滯留性。其對HSF的作用證實了體外細胞增殖和細胞遷移過程中細胞運動性的本質(zhì)降低，這對下調(diào)HSF中轉(zhuǎn)化生長因子-β1(TGF-β1)的分泌，提高Smad7的表達水平具有重要作用。 結(jié)論：制備的TSA自溶性微針有助于解決增生性疤痕問題，經(jīng)工藝優(yōu)化后具有穩(wěn)定的皮膚滯留性效果。

    Abstract:
    Objective: Hypertrophic scars (HS) are a variety of skin tissue fibrosis disease that occurs in human skin, the effective therapeutic method of which is still inaccessible up to now. As a bioactive constituent of a well-known medical plant, Salvia miltiorrhiza (Danshen in Chinese), tanshinone IIA (TSA) is reported to inhibit cell proliferation in HS. Therefore, the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site. The possible mechanism of action in suppressing HS was studied using human skin fibroblasts (HSF). Methods: Tanshinone IIA self-dissolving microneedles (TSA-MN) was prepared using a negative mold casting method. The prescription process of microneedle was optimized by Box-Behnken effect surface method. Different media were selected to investigate the ability of transdermal absorption and in vitro release. Furthermore, according to Cell Counting Kit-8 (CCK8) method as well as the Western blot method, the effect of TSA-MN on the biological characteristics of HSF was investigated. Results: With remarkable slow release effect and dermal retention, the release and transdermal properties of TSA-MN in vitro were better than both TSA and ordinary dosage forms. Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration in vitro, which plays a significant role in down-regulating the secretion of transforming growth factor-β1(TGF-β1) in HSF and increasing the expression level of Smad7. Conclusion: The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars, with a stable dermal retention effect after process optimization.

    關(guān)鍵詞:
    人皮膚成纖維細胞;肥厚性疤痕;丹參酮IIA;丹參酮IIA自溶微針;轉(zhuǎn)化生長因子-β1

    Keywords:


    Project Supported:
    This study was supported by the National Natural Science Foundation of China (No.82173982, 2021); the Guangdong Natural Science Project (No. 2018A0303130234) and Excellent Young Teachers Training Project in Higher Education of Guangdong (No. YQ2015099).

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