Department of Pharmacy, National University of Singapore, Singapore.
Int J Nanomedicine. 2012;7:3143-54. doi: 10.2147/IJN.S32000. Epub 2012 Jun 22.
Recent interest in biocompatible polymeric microneedles for the delivery of biomolecules has propelled considerable interest in fabrication of microneedles. It is important that the fabrication process is feasible for drug encapsulation and compatible with the stability of the drug in question. Moreover, drug encapsulation may offer the advantage of higher drug loading compared with other technologies, such as drug coating.
In this study, we encapsulated a model protein drug, namely, bovine serum albumin, in polymeric microneedles by photolithography. Drug distribution within the microneedle array was found to be uniform. The encapsulated protein retained its primary, secondary, and tertiary structural characteristics. In vitro release of the encapsulated protein showed that almost all of the drug was released into phosphate buffered saline within 6 hours. The in vitro permeation profile of encapsulated bovine serum albumin through rat skin was also tested and shown to resemble the in vitro release profile, with an initial release burst followed by a slow release phase. The cytotoxicity of the microneedles without bovine serum albumin was tested in three different cell lines. High cell viabilities were observed, demonstrating the innocuous nature of the microneedles.
The microneedle array can potentially serve as a useful drug carrier for proteins, peptides, and vaccines.
最近,人们对生物相容性聚合物微针在生物分子传递方面的应用产生了浓厚的兴趣,这促使人们对微针的制造技术产生了极大的兴趣。重要的是,制造工艺应便于药物包封,并且与所涉及药物的稳定性兼容。此外,与其他技术(如药物涂层)相比,药物包封可能具有更高的药物载药量的优势。
在本研究中,我们通过光刻技术将模型蛋白药物(即牛血清白蛋白)包封在聚合物微针中。发现药物在微针阵列中的分布均匀。包封的蛋白质保留了其一级、二级和三级结构特征。体外释放实验表明,在 6 小时内几乎所有药物都释放到磷酸盐缓冲盐溶液中。还测试了包封的牛血清白蛋白通过大鼠皮肤的体外渗透情况,并显示出与体外释放曲线相似的特征,即初始释放爆发后是缓慢释放阶段。在三种不同的细胞系中测试了不含牛血清白蛋白的微针的细胞毒性。观察到高细胞活力,表明微针具有无害性。
微针阵列有可能成为蛋白质、肽和疫苗的有用药物载体。