US EPA

4947114 

Journal Article 

Topical delivery of anthramycin I. Influence of neat solvents 

Haque, T; Rahman, KM; Thurston, DE; Hadgraft, J; Lane, ME 

2017 

Yes 

European Journal of Pharmaceutical Sciences
ISSN: 0928-0987
EISSN: 1879-0720 

104 

188-195 

English 

28373034 

10.1016/j.ejps.2017.03.043 

WOS:000405251600020 

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.