ENGINEERED LIPOSOMAL PARTICLES CONTAINING CORE-LOADED PRO-DRUGS FOR THE CONTROLLED RELEASE OF CAMPTOTHECINS

摘要

A liposome composition includes an entrapped camptothecin ester derivative loaded predominantly in the aqueous core of the liposomal particle. More particularly the invention relates to controlled release formulations that entail the liposomal core-loading of camptothecin-20-esters (CPT-20-OR). Through judicious choice of liposomal encapsulation methodologies, lipid ingredients, and the choice of the R=CO[CH2]nNH2HC1 functionally of the CPT-20-OR, formulations are developed which release camptothecin pro-drug from the liposomal particle. Upon reaching the outside of the particle and gaining exposure to the physiological mileau (i.e. pH 6.8 to 7.4) at the tumor site, the glycinate esters decompose to generate the active lactone of camptothecins which are potent inhibitors of DNA topoisomerase I and potent anti-cancer agents.