Novel 3-O-pegylated carboxylate and 3-O-pegylated carbamate prodrugs of naltrexone for microneedle-enhanced transdermal delivery

作者：Yerramreddy Thirupathi Reddy; Milewski Mikolaj; Penthala Narsimha Reddy; Stinchcomb Audra L; Crooks Peter A^*

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(11): 3280-3283.

DOI：10.1016/j.bmcl.2010.04.049

• Naltrexone prodrugs
• Alcohol dependence and opioid addiction
• Microneedle-enhanced transdermal delivery

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.

• 出版日期2010-6-1