Abstract

The present investigation reports the formulation of resealed erythrocytes (RBCs) as carriers for the anticancer agent, 5-fluorouracil (5-FU). The preswell dilution technique was adopted for loading and various formulation conditions like preswelling point, drug concentration, time of contact, point of lysis, resealing point, incubation period and cross linking conditions were optimized. Nearly spherical RBCs with 6.9±1.014 pm size, 88% cell recovery and 43.84±1.54% drug loading were obtained after optimizat1on. The 5-FU loaded RBCs were evaluated with respect to osmotic fragility, turbulence shock studies, osmotic shock studies, In vitro 5-FU and hemoglobin (Hb) leaching. It was concluded that the loading procedure had reduced the resistance of the RBCs to osmotic and turbulence shock but the cell shape and integrity remain unaffected. Due to cross linking, stress resistance was improved and 5-FU and Hb leaching during storage were reduced. In vivo studies in healthy rats after i.v. administration of loaded RBCs showed a significant 5-FU accumulation in spleen and lungs as compared to that from plain 5-FU solution. These findings point to the potential utility of resealed RBCs as site specific carriers for improving therapy of 5-FU, especially in tumors of lungs.