title: Skin delivery potency and antitumor activities of temozolomide ester prodrugs.
abstract: Clinical trials have shown temozolomide to be an effective agent for treatment of malignant melanoma. In order to investigate its suitability for delivery via the skin, a series of temozolomide esters was synthesized as prodrugs. In vitro assays demonstrated temozolomide, temozolomide acid and the hexyl ester equi-effective against selected cancer cell lines. The susceptibility of the esters to enzyme hydrolysis and their effectiveness for application to the skin were investigated. The esters effectively diffuse through rat skin and the hexyl ester demonstrated profound potency for penetrating through skin. Topical application of 5% (w/v) hexyl ester in DMSO solution on a mouse model demonstrated a significant inhibition of tumor growth. These results suggest that temozolomide esters could be an effective alternative to temozolomide in the treatment of skin cancer.
authors.affiliation: School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, Westmidland B4 7ET, UK.
authors.forename: Panassaya
authors.initials: P
authors.lastname: Suppasansatorn
authors.forename: Guocheng
authors.initials: G
authors.lastname: Wang
authors.forename: Barbara R
authors.initials: BR
authors.lastname: Conway
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004950:Esterases / Q000378:metabolism; D004952:Esters / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000201:enzymology; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011355:Prodrugs / Q000627:therapeutic use*; D051381:Rats; D012867:Skin / Q000187:drug effects*; D012878:Skin Neoplasms / Q000188:drug therapy*; D013552:Swine; D000077204:Temozolomide; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004952:Esters; D011355:Prodrugs; D003606:Dacarbazine; D004950:Esterases; D000077204:Temozolomide