Factors influencing the encapsulation of thioguanine in DRV liposomes

Abstract

Thioguanine, a chemotherapeutic drug employed in the treatment of leukemia, is, like other amphiphilic drugs, very permeant and presents a high ability to escape from the liposomal membrane. For this reason, it is very important to know which parameters can enhance the relatively low encapsulation of thioguanine. In this way, the influence of four factors (pH, content of cholesterol, charge of lipids, and time of sonication) on the encapsulation of such drug in dehydration-rehydration liposomes was studied using a 2 4 factorial design. In this study, the maximal encapsulation efficiency obtained was 14.07 mmol/mol of lipid and time of sonication was the unique factor whose influence on the encapsulation was statistically significant ( P < 0.05). The energy input concomitant to higher periods of sonication seems to facilitate the entrapment of the drug into the bilayer. Among the two-way interactions, time charge and pH-charge presented levels of significance less than 0.05. In liposomes with negative charge (10% phosphatidic acid), time of sonication barely influenced on the encapsulation, but in stearylamine-containing liposomes, higher times of sonication were necessary to achieve a better yield of encapsulation. More complex was the effect of the pH-charge interaction. At pH 4.7, liposomes with phosphatidic acid favoured the encapsulation, while at pH 7.4, liposomes with stearylamine encapsulated more drug. The different extent of encapsulation in the function of pH and charge only could be explained by the different charge born by the positive and negative liposomes depending on the pH.