Enhanced in vitro efficacy for inhibiting hypertrophic scar by bleomycin-loaded dissolving hyaluronic acid microneedles
Enhanced in vitro efficacy for inhibiting hypertrophic scar by bleomycin-loaded dissolving hyaluronic acid microneedles
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负载博莱霉素的溶解性透明质酸微针增强抑制增生性疤痕的体外功效
DOI：
10.1039/c9tb01449g
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发表时间：
2019
影响因子：
7
通讯作者：
Zhu Jintao
中科院分区：
文献类型：
--
作者：
Xie Ying;Wang Hua;Mao Jinzhu;Li Yuce;Hussain Mubashir;Zhu Jinjin;Li Yan;Zhang Lianbin;Tao Juan;Zhu Jintao
增生性瘢痕是一种广泛的皮肤病，影响患者的信心和生活质量。病灶内注射博莱霉素是治疗增生性瘢痕最常用的方法之一，然而，这总是带来疼痛，需要长期治疗。为了克服这些限制，迫切需要能够无痛、自我给药、快速起效和良好生物利用度的博来霉素递送的新方法。在这项研究中，我们开发了由透明质酸（HA）制成的载有博来霉素的溶解性微针（BMN），具有良好的水溶性和增强的抑制增生性瘢痕的功效。所制备的BMN具有足够的机械强度，可以在离体条件下刺穿猪皮肤，插入深度超过300 μm。BMN能迅速溶解，1 min内释放20%，10 min内释放52%，经BMN处理后的皮肤在3 h内即可恢复原状，具有良好的生物相容性。此外，HA基质还保持了博莱霉素的稳定性和活性。此外，我们还发现由HA和博来霉素组成的BMN可以抑制体外培养的人增生性瘢痕成纤维细胞（hHSFs）的增殖和转化生长因子-β 1（TGF-β1）的分泌。因此，负载博来霉素的溶解性HA微针提供了以方便、有效和微创的方式治疗增生性瘢痕的潜在途径。
Hypertrophic scarring is a widespread skin disorder that affects a patient's confidence and quality of life. Intralesional injection of bleomycin is one of the most commonly employed treatments for hypertrophic scars, which, however, always brings pain and requires long-term treatment. To overcome these limitations, new methods for bleomycin delivery enabling painlessness, self-administration, the fast onset of action, and good bioavailability are urgently needed. In this study, we developed bleomycin-loaded dissolving microneedles (BMN) made up of hyaluronic acid (HA) with excellent aqueous solubility and enhanced efficacy for inhibiting hypertrophic scars. The as-obtained BMN possesses sufficient mechanical strength to pierce porcine skin ex vivo with an insertion depth of over 300 μm. Moreover, BMN can dissolve rapidly and release 20% of loaded bleomycin within 1 min and 52% within 10 min, and the BMN-treated skin could recover to its original status within 3 h, demonstrating good biocompatibility. Besides, the HA matrix also maintains the stability and activity of bleomycin. Furthermore, we show that BMN consisting of HA and bleomycin can inhibit the proliferation of human hypertrophic scar fibroblasts (hHSFs) and the secretion of transforming growth factor-β (TGF-β1) in vitro. Therefore, bleomycin-loaded dissolving HA microneedles provide a potential route to treat hypertrophic scars in a convenient, efficient, and minimally invasive manner.