Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
Bioorg Med Chem Lett. 2010 Jun 1;20(11):3280-3. doi: 10.1016/j.bmcl.2010.04.049. Epub 2010 Apr 18.
A small library of novel 3-O-pegylated carboxylate prodrugs (4a-4b) and 3-O-pegylated carbamate prodrugs (9a-9b) of naltrexone were synthesized. The goal behind the design of these prodrugs was to investigate their potential for microneedle-enhanced transdermal delivery. All the synthesized 3-O-pegylated carboxylate prodrugs (4a-4b) and 3-O-pegylated carbamate prodrugs (9a-9b) of naltrexone were found to have adequate stability in a transdermal formulation and improved apparent solubility compared to naltrexone. Viscosity effects were postulated to be responsible for the observed non-linearity in the flux-concentration profile of these prodrugs.
我们合成了一系列新型的纳曲酮 3-O-聚乙二醇羧酸酯前药（4a-4b）和 3-O-聚乙二醇氨基甲酸酯前药（9a-9b）。设计这些前药的目的是研究它们经微针增强透皮给药的潜力。所有合成的纳曲酮 3-O-聚乙二醇羧酸酯前药（4a-4b）和 3-O-聚乙二醇氨基甲酸酯前药（9a-9b）在透皮制剂中都表现出足够的稳定性，与纳曲酮相比，表观溶解度也有所提高。我们推测，黏度效应是这些前药的通量-浓度曲线呈现非线性的原因。
