School of Materials Science and Engineering and Department of Nanobio Materials and Electronics, Gwangju Institute of Science and Technology, 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, South Korea.
J Control Release. 2012 Jan 30;157(2):272-8. doi: 10.1016/j.jconrel.2011.08.013. Epub 2011 Aug 16.
In spite of several intrinsic and distinct advantages, a topical and transdermal administration of drugs has been limited mainly due to very low permeability of drugs across skin. Especially, it is generally regarded that hydrophilic macromolecules such as proteins, peptides, and vaccines cannot penetrate across skin. In this study, we demonstrated that chitosan-conjugated, Pluronic-based nano-carrier (nanogel) can act as an efficient delivery vehicle of hydrophilic proteins across human skin. The functional nano-carrier (<100 nm in size), chemically-crosslinking Pluronic F 127 with chitosan conjugation, is flexible and soft with reservoir characteristics for biomacromolecules. The in-vitro permeation experiments through human cadaver skin revealed remarkable permeability of hydrophilic proteins of various sizes including FITC-BSA (67 kDa) and FITC-Insulin (6 kDa) by direct penetration of the nano-carrier across skin. The bioactivity post-permeation of proteins via the functional nano-carrier was also confirmed by delivering ß-galactosidase. Results presented in this paper suggest the use of chitosan-conjugated flexible nano-carrier as a novel platform for transcutaneous delivery of hydrophilic macromolecules and other drug-delivery applications.
尽管具有多种内在且独特的优势，但药物的局部和透皮给药主要受到药物在皮肤中极低渗透性的限制。特别是，人们普遍认为亲水性大分子，如蛋白质、肽和疫苗，无法穿透皮肤。在本研究中，我们证明了壳聚糖缀合的、基于普朗尼克的纳米载体（纳米凝胶）可以作为亲水性蛋白质跨过人皮肤的有效递送载体。该功能纳米载体（<100nm 大小）通过壳聚糖缀合化学交联普朗尼克 F127，具有生物大分子的储库特性，是灵活柔软的。通过人体尸体皮肤的体外渗透实验表明，纳米载体可直接穿透皮肤，使各种大小的亲水性蛋白质（包括 FITC-BSA（67kDa）和 FITC-胰岛素（6kDa））具有显著的渗透性。通过功能性纳米载体传递蛋白质的生物活性也通过递送β-半乳糖苷酶得到了证实。本文的研究结果表明，壳聚糖缀合的柔性纳米载体可作为亲水性大分子经皮传递的新型平台，以及其他药物传递应用。
