Molecular perspective of efficiency and safety problems of chemical enhancers: bottlenecks and recent advances.

Chemical penetration enhancer (CPE) is a preferred approach to improve drug permeability through the skin, due to its unique advantages of simple use and high compatibility. However, CPEs efficiency and safety problems frequently arise, which greatly restrains the further application in transdermal drug delivery systems (TDDS). To get access to the root of problems, the efficiency and safety of CPEs are reviewed especially from molecular perspectives, which include (1) the possible factors of CPEs low efficiency; (2) the possible contribution of CPEs in the evolution of safety problems such as skin irritation and allergic reaction; (3) the interactive relationship between CPEs efficiency and safety, as well as the bottlenecks of achieving their balance. More importantly, based on these, recent advances are summarized in improving efficiency or safety of CPEs, which offers a guidance of rationally selecting CPEs in future research.