Synthesis and Stability of a Covalently Linked Liposome-Phenol Ester Model Prodrug

Abstract

This study examines the feasability of covalently bonding a drug to a liposomal wall component to yield a potential liposome prodrug. The model compound chosen, p-nitrophenol, was esterified with the stearic acid present in liposomes employing the coupling agents 1-ethyl-3-(3 dimethyl aminopropyl) carbodiimide (EDCI) and dicyclohexyl carbodiimide (DCC). Reactions conducted with EDCI in distilled water or with DCC in either distilled water or phosphate buffer yielded >80% pnitrophenyl stearate. When EDCI was used in the presence of phosphate buffer, the ester yield was reduced to ∼40%. The time for ten percent degradation (Tg0) of the liposome ester was evaluated at 37°C in the pH range 1-11. A ∼3 to 17 fold rate enhancement was observed when esterase was added to the buffered solutions.