Follicular delivery of erythromycin from nonionic liposomes and emulsions.

The results of studies on the topical delivery of erythromycin presented in this dissertation underscore the need to re-examine a number of established views of how formulation factors affect drug delivery. The major issues addressed in this study were designed to improve the targeted topical delivery of the antibiotic, erythromycin, to follicles and sebaceous glands in order to maximize its therapeutic efficacy in the treatment of acne. The first involves the hitherto ignored importance of the follicular route as a major alternative for transport of drugs. The efficiency of transport of erythromycin (EM) into pilosebaceous units from various formulations was assessed with the hamster ear model. Isopropyl myristate (IPM)-based liposomal emulsions were found to be superior to the other formulations tested in delivering EM into sebaceous glands. The demonstration of selective and enhanced delivery via the follicular route by these novel nonionic liposomal emulsions suggests that the follicular route can be exploited through appropriate design of the drug vehicle. The second major issue addressed in this study is the popular misconception that ethanolic solutions provide unencumbered access of the drug to follicles and sebaceous glands. Alcohol-based formulations delivered very low levels of erythromycin into the hairless mouse skin as well as the hamster ears. The evidence presented in this study is compelling and strongly argues for a reassessment of the magical role of ethanol. The third major and interrelated issue is the elucidation of thermodynamic factors that control the rate and extent of follicular deposition. The failure of ethanolic solutions to deposit EM into the pilosebaceous units coupled with the enhancement in follicular deposition with IPM-based formulations suggests that the drug and/or ethanol may be incompatible with the follicular sebum environment and that the presence of IPM obviates this incompatibility. The finding that the addition of IPM to alcoholic solutions increased deposition of drug in a dramatic manner suggests that sebum is indeed the major thermodynamic deterrent to follicular entry of drugs. Autoradiographic evidence is presented to confirm that IPM-based formulations transport drugs across the transfollicular route.Ph.D.Health and Environmental SciencesPharmaceutical sciencesPharmacy sciencesPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130502/2/9732106.pd