Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, Kentucky 40536-0082, USA.
J Pharm Sci. 2013 May;102(5):1458-67. doi: 10.1002/jps.23469. Epub 2013 Feb 15.
Microneedle (MN) enhanced transdermal drug delivery enables the transport of a host of molecules that cannot be delivered across the skin by passive diffusion alone. However, the skin being a self-regenerating organ heals itself and thus prevents delivery of molecules through micropores for a 7-day time period, the ideal transdermal delivery goal. Hence, it is necessary to employ a second drug molecule, a cyclooxygenase inhibitor to enhance pore lifetime by decreasing local subclinical inflammatory response following MN treatment. A codrug approach using a 3-O-ester codrug of the model drug naltrexone (NTX) with diclofenac (DIC), a cyclooxygenase inhibitor, was tested in vitro as well as in vivo to look at stability, bioconversion and permeation. The results indicated that the approach could be useful for transdermal drug delivery of NTX from a single patch for a week, but stability and solubility optimization will be required for the codrug before it can deliver significant levels of NTX into the plasma. The skin concentration of DIC was high enough to keep the pores open in vivo in a hairless guinea pig model as demonstrated by day seven pore visualization studies.
微针（MN）增强的经皮药物输送使许多分子能够通过被动扩散以外的方式输送到皮肤中。然而，皮肤是一个自我再生的器官，它会自行愈合，从而防止分子通过微孔输送，这是理想的经皮输送目标。因此，有必要使用第二种药物分子，环氧化酶抑制剂，通过减少 MN 治疗后的局部亚临床炎症反应来延长微孔寿命。使用模型药物纳曲酮（NTX）与环氧化酶抑制剂双氯芬酸（DIC）的 3-O-酯前药的共药方法在体外和体内进行了测试，以研究其稳定性、生物转化和渗透。结果表明，该方法可用于从单个贴片一周内透皮输送 NTX，但在共药能够将大量 NTX 输送到血浆中之前，需要对其进行稳定性和溶解度优化。在无毛豚鼠模型中，通过第 7 天的微孔可视化研究表明，DIC 的皮肤浓度足以保持体内微孔开放。
