Preparation of liposome-encapsulated anti-tumor drugs; Relationship between lipophilicity of drugs and in vitro drug release.

Abstract

Liposomal encapsulation of drugs by a reverse-phase evaporation vesicle (REV) method was carried out, and the relation between the in vitro release rates and the lipophilicity of drugs was investigated. Anti-tumor drugs such as carboquone (CQ), nimustine (ACNU), nimustine hydrochloride (ACNU-HCl), cytosine arabinoside (Ara-C), 5-fluorouracil (5-FU) and related compounds were used as model drugs. Encapsulation of the drugs in liposomes was concluded to have no relation with the partition coefficients of the drugs, whereas the in vitro release rate was highly correlated to the partition coefficient and it was evident that the drug was released more slowly when the partition coefficient was lower. Therefore, to achieve sustained release of a drug by means of liposomal encapsulation, it would be necessary to decrease the partition coefficient of the drug by converting it into the hydrochloride form, as in the case of ACNU, or by forming the sodium salt of the drug, if the drug has a carboxylic acid group.