Chen Fan, Yan Qinying, Yu Yang, Wu Mei X
Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, MA 02114, USA; Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Life Sciences School of Hubei University, 368 Youyi Road, Wuhan 430062, China.
Wellman Center for Photomedicine, Massachusetts General Hospital (MGH), Department of Dermatology, Harvard Medical School (HMS), Boston, MA 02114, USA; College of Pharmaceutical Sciences, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310032, China.
J Control Release. 2017 Jun 10;255:36-44. doi: 10.1016/j.jconrel.2017.03.397. Epub 2017 Apr 5.
Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin.
减毒活卡介苗（BCG）是迄今为止全球唯一获批用于预防结核病的疫苗。它必须通过皮内注射才能生效，这会导致严重的皮肤炎症，有时还会留下永久性疤痕。为了尽量减少副作用，我们开发了一种新型微针阵列（MNA），它可以以无痛、无损伤且可自行施用的方式将减毒冻干卡介苗粉末输送到表皮。该MNA由生物相容性且可溶解的透明质酸制成，每个微针的基部形成一个深腔，卡介苗粉末可直接包装在其中。封装在腔中的卡介苗疫苗的活力以及载有粉末的MNA的机械强度在室温下储存两个多月前后没有明显变化。将MNA插入皮肤后，单个微针杆被来自表皮和真皮上层的组织液溶解，使粉末暴露于表皮组织。粉末吸收组织液，缓慢溶解，并在一天内随着组织液的流入扩散到表皮中。与引起严重炎症和瘀伤的皮内接种形成鲜明对比的是，卡介苗-MNA接种不会引起明显的皮肤刺激。虽然几乎不会引起皮肤刺激，但无论是通过体液免疫还是细胞免疫评估，卡介苗-MNA的接种效果都与皮内免疫相当。这种载有粉末且可溶解的MNA代表了一种将减毒活疫苗粉末充分输送到皮肤中的新技术。
