Synthesis and transdermal penetration of cytarabine and selected amide, ester and carbamate derivatives

摘要: Cancer is reported to be one of the top ten leading causes death worldwide and its treatment poses a number challenges. Cytarabine deoxycytidine analogue commonly used in haematological malignant diseases. Its clinical utility, however, severely limited by short plasma half-life due catabolic action nucleoside deaminases. Due cell cycle (S-phase) specificity cytarabine, prolonged exposure cells cytarabine's cytotoxic concentrations essential achieve maximum activity often achieved more invasive inconvenient modes administration such as continuous intravenous infusion. Transdermal drug delivery systems (TO OS), on other hand, have potential this sustained release which useful for drugs with biological half-lives without inconvenience associated However, not .all are suited TDDS. Owing good barrier function skin mainly lipophilic outermost layer, stratum corneum, most hydrophilic structures permeate too slowly therapeutic benefit. This hydrogen-bonding functionality permeant drastically retard permeation. known high hydrophilicity plurality polar functional groups capable hydrogen bonding. Therefore, it becomes apparent that cytarabine would easily skin. The disadvantages TDDS include irritation, possible side effects. Prodrug approach could circumvent these setbacks. has been investigated enhance dermal transdermal penetration unfavourable intrinsic properties showed promising outcomes. Increased if delivered via derivative better physicochemical penetration. aims study were determine synthesized amide, ester carbamate derivatives establish correlation, any, between selected properties. alkylamide (5 compounds), alkylester (6 compounds) Compounds) standard chemical procedures, their confirmed NMR MS they evaluated using human epidermis model. flux values determined vitro Franz diffusion methodology. Quantification compounds was HPLC. Selected (aqueous lipid solubility; melting point log D) assessed any correlation parameters compounds.