Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
Biomaterials. 2012 Jul;33(20):5156-65. doi: 10.1016/j.biomaterials.2012.03.056. Epub 2012 Apr 7.
This work presents an approach to codelivering transdermally two model drugs, Alexa 488 and Cy5, in sequence, based on a system of polyvinylpyrrolidone microneedles (PVP MNs) that contain pH-responsive poly(d,l-lactic-co-glycolic acid) hollow microspheres (PLGA HMs). The MN system provides the green fluorescence of Alexa 488 in PVP MNs, the red fluorescence of the DiI-labeled PLGA shell of HMs, and the cyan fluorescence of Cy5 in their aqueous core. Combined together, the prepared MN arrays support the localization of the HMs and the monitoring of the release profiles of model drugs within the skin tissues. The key component of this system is NaHCO(3), which can be easily incorporated into HMs. After HMs are treated with an acidic solution (simulating the skin pH environment), protons (H(+)) can rapidly diffuse through the free volume in the PLGA shells to react with NaHCO(3) and form a large number of CO(2) bubbles. This effect generates pressure inside the HMs and creates pores inside their PLGA shells, releasing the encapsulated Cy5. Test MNs were strong enough to be inserted into rat skin without breaking. The PVP MNs were significantly dissolved within minutes, and the first model drug Alexa 488, together with HMs, were successfully deposited into the tissues. Once in the acidic environment of the skin, the released HMs started to release Cy5 and continued to spread throughout the neighboring tissues, in a second step of the release of the drug. This approach can be used clinically to codeliver sequentially and transcutaneously a broad range of drugs.
本工作提出了一种基于聚维酮（PVP）微米针（MN）系统的方法，可顺序递呈两种模型药物，即阿利昔单抗（Alexa 488）和 Cy5，该系统含有 pH 响应性聚（DL-丙交酯-乙交酯）中空微球（PLGA HM）。MN 系统提供 PVP MN 中的 Alexa 488 的绿色荧光、HM 的 DiI 标记的 PLGA 壳的红色荧光和其水核中的 Cy5 的青色荧光。组合在一起，制备的 MN 阵列支持 HM 的定位和模型药物在皮肤组织内的释放曲线的监测。该系统的关键组分是 NaHCO3，可以容易地掺入到 HM 中。HM 经酸性溶液处理（模拟皮肤 pH 环境）后，质子（H+）可快速扩散通过 PLGA 壳的自由体积，与 NaHCO3 反应，形成大量的 CO2 气泡。该效应在 HM 内产生压力，并在其 PLGA 壳内产生孔，释放包封的 Cy5。测试 MN 足够坚固，可插入大鼠皮肤而不折断。PVP MN 在数分钟内显著溶解，第一模型药物 Alexa 488 与 HM 一起成功地沉积到组织中。一旦进入皮肤的酸性环境，释放的 HM 开始释放 Cy5，并在药物释放的第二步中继续扩散到邻近的组织中。这种方法可在临床上用于顺序和经皮递呈广泛范围的药物。
