Xie Yu, Xu Bai, Gao Yunhua
Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China.
Nanomedicine. 2005 Jun;1(2):184-90. doi: 10.1016/j.nano.2005.03.001.
This article reports an in vitro study of microneedle-array-enhanced transdermal transport of model drug compounds dispersed in chitosan films. Each microneedle array has 400 out-of-plane, needle-shaped microstructures fabricated using micro-electro-mechanical systems (MEMS) technology to ensure adequate mechanical strength and high precision, and consistency. A nanometer coating on the microneedles ensured the biocompatibility that is important in the application of transdermal drug delivery. Model drugs selected to investigate skin permeation in vitro were calcein, a small molecule (molecular weight, 623 d) that has little skin penetration, and bovine serum albumin (BSA) (molecular weight, 66,000 d), a hydrophilic biological macromolecule. A Franz permeation cell was used to characterize the permeation rate of calcein and BSA through the rat skin. The transdermal transport behavior of BSA was investigated from solid films coated on the surface of microneedle arrays with various chitosan concentrations, film thicknesses, and BSA contents. The BSA permeation rate decreased with the increase of the chitosan concentration; the thicker the film, the slower the permeation rate. In addition, the permeation rate increased with the increase of BSA loading dose. A linear relationship existed between the permeation rate and the square root of the BSA loading dose. Results showed that the chitosan hydrophilic polymer film acts as a matrix that can regulate the BSA release rate. The controlled delivery of BSA can be achieved using the BSA-containing chitosan matrix film incorporated with the microneedle arrays. This will provide a possible way for the transdermal delivery of macromolecular therapeutic agents such as proteins and vaccines.
本文报道了一项关于微针阵列增强分散在壳聚糖膜中的模型药物化合物经皮转运的体外研究。每个微针阵列具有400个使用微机电系统(MEMS)技术制造的平面外针状微结构,以确保足够的机械强度、高精度和一致性。微针上的纳米涂层确保了生物相容性,这在经皮给药应用中很重要。选择用于体外研究皮肤渗透的模型药物是钙黄绿素,一种皮肤渗透性小的小分子(分子量623 d),以及牛血清白蛋白(BSA)(分子量66,000 d),一种亲水性生物大分子。使用Franz渗透池来表征钙黄绿素和BSA通过大鼠皮肤的渗透速率。研究了不同壳聚糖浓度、膜厚度和BSA含量的微针阵列表面涂覆的固体膜中BSA的经皮转运行为。BSA的渗透速率随壳聚糖浓度的增加而降低;膜越厚,渗透速率越慢。此外,渗透速率随BSA负载剂量的增加而增加。渗透速率与BSA负载剂量的平方根之间存在线性关系。结果表明,壳聚糖亲水性聚合物膜作为一种基质,可以调节BSA的释放速率。使用结合微针阵列的含BSA壳聚糖基质膜可以实现BSA的控释。这将为蛋白质和疫苗等大分子治疗剂的经皮递送提供一种可能的途径。