Biomaterial Database

Enhanced delivery of zidovudine through rat and human skin via ester prodrugs. 1990

T Seki, and T Kawaguchi, and K Juni

Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.

In an attempt to improve the skin delivery characteristics of Zidovudine (AZT, azidothymidine), five aliphatic esters (acetate, butyrate, hexanoate, octanoate, and decanoate) of AZT were synthesized and assessed as prodrugs of AZT. While the water solubility of the esters is lower than that of AZT, the solubilities in isopropylmyristate (IPM) and the partition coefficients (n-octanol:buffer) are higher. Susceptibility to enzymatic hydrolysis in the rat skin homogenate increases as the acyl chain of the ester is lengthened. Among the esters, acetate (C2-AZT) and hexanoate (C6-AZT) showed 2.4- and 4.8-fold enhanced permeation in human skin from an apolar vehicle (IPM) relative to application of AZT itself, respectively.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D010539	Permeability	Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.	Permeabilities
D011355	Prodrugs	A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.	Drug Precursor,Drug Precursors,Pro-Drug,Prodrug,Pro-Drugs,Precursor, Drug,Precursors, Drug,Pro Drug,Pro Drugs
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004952	Esters	Compounds derived from organic or inorganic acids in which at least one hydroxyl group is replaced by an –O-alkyl or another organic group. They can be represented by the structure formula RCOOR’ and are usually formed by the reaction between an acid and an alcohol with elimination of water.	Ester
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000279	Administration, Cutaneous	The application of suitable drug dosage forms to the skin for either local or systemic effects.	Cutaneous Drug Administration,Dermal Drug Administration,Drug Administration, Dermal,Percutaneous Administration,Skin Drug Administration,Transcutaneous Administration,Transdermal Administration,Administration, Dermal,Administration, Transcutaneous,Administration, Transdermal,Cutaneous Administration,Cutaneous Administration, Drug,Dermal Administration,Drug Administration, Cutaneous,Skin Administration, Drug,Administration, Cutaneous Drug,Administration, Dermal Drug,Administration, Percutaneous,Administrations, Cutaneous,Administrations, Cutaneous Drug,Administrations, Dermal,Administrations, Dermal Drug,Administrations, Percutaneous,Administrations, Transcutaneous,Administrations, Transdermal,Cutaneous Administrations,Cutaneous Administrations, Drug,Cutaneous Drug Administrations,Dermal Administrations,Dermal Drug Administrations,Drug Administrations, Cutaneous,Drug Administrations, Dermal,Drug Skin Administrations,Percutaneous Administrations,Skin Administrations, Drug,Skin Drug Administrations,Transcutaneous Administrations,Transdermal Administrations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012869	Skin Absorption	Uptake of substances through the SKIN.	Absorption, Skin,Intracutaneous Absorption,Intradermal Absorption,Percutaneous Absorption,Transcutaneous Absorption,Transdermal Absorption,Absorption, Intracutaneous,Absorption, Intradermal,Absorption, Percutaneous,Absorption, Transcutaneous,Absorption, Transdermal,Absorptions, Intracutaneous,Absorptions, Intradermal,Absorptions, Percutaneous,Absorptions, Skin,Absorptions, Transcutaneous,Absorptions, Transdermal,Intracutaneous Absorptions,Intradermal Absorptions,Percutaneous Absorptions,Skin Absorptions,Transcutaneous Absorptions,Transdermal Absorptions
D012995	Solubility	The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)	Solubilities