TY - JOUR SN - 1879-0720 UR - http://doi.org/10.1016/j.ejps.2017.03.043 ID - discovery1546520 N2 - Anthramycin (ANT) was the first pyrrolobenzodiazepine (PBD) molecule to be isolated, and is a potent cytotoxic agent. Although the PBD family has been investigated for use in systemic chemotherapy, their application in the management of actinic keratoses (AK) or skin cancer has not been investigated to date. In the present work, anthramycin (ANT) was selected as a model PBD compound, and the skin penetration of the molecule was investigated using conventional Franz diffusion cells. Finite dose permeation studies of ANT were performed using propylene glycol (PG), 1,3-butanediol (BD), dipropylene glycol (DiPG), Transcutol P® (TC), propylene glycol monocaprylate (PGMC), propylene glycol monolaurate (PGML) and isopropyl myristate (IPM). The skin penetration of BD, DiPG, PG and TC was also measured. Penetration of ANT through human skin was evident for TC, PG and PGML with the active appearing to "track" the permeation of the vehicle in the case of TC and PG. Deposition of ANT in skin could be correlated with skin retention of the vehicle in the case of IPM, PGMC and PGML. These preliminary findings confirm the ability of ANT to penetrate human skin and, given the potency of the molecule, suggest that further investigation is justified. Additionally, the findings emphasise the critical importance of understanding the fate of the excipient for the rational design of topical formulations. KW - Anthramycin KW - Franz diffusion cell KW - PBDs KW - Permeation KW - Pyrrolobenzodiazepines KW - Skin cancer KW - Solvents KW - Topical therapy A1 - Haque, T A1 - Rahman, KM A1 - Thurston, DE A1 - Hadgraft, J A1 - Lane, ME JF - European Journal of Pharmaceutical Sciences EP - 195 AV - public VL - 104 SP - 188 Y1 - 2017/06/15/ TI - Topical delivery of anthramycin I. Influence of neat solvents N1 - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions. ER -