The use of cholesteryl pullulan for the preparation of stable vincristine liposomes

An improved method for the synthesis of cholesteryl pullulan has been developed. This method involves 1,4-diazabicyclo(2,2,2)octane as a catalyst which greatly reduced the reaction time. The synthesized cholesteryl pullulan (CHP) was characterized using FT-IR and FT-NMR and used for coating the vincristine liposomes: Phosphatidylcholine liposomes with and without vincristine sulfate were prepared by-a sonication method. The percentage of vincristine encapsulated in the liposomes was determined by solubilizing the bilayers using Triton-X 100. The liposomes were coated with two different concentrations of CHP solution (PC/CHP weight ratio of 3:0.5 [CHP-CL1] and PC/CHP weight ratio of 3:1 [CHP-CL2]). Both the CHP coated liposomes were characterized by transmission electron microscopy and turbidity measurement: Transmission electron micrograph showed the spherical shape of the CHP-CL1 and CHP-CL2 liposomes. The micrograph further showed the complete coat of CHP at the outermost surface of the CHP-CL2 liposomes. The average sizes of CHP-CL1 and CHP-CL2 liposomes are 340 and 350 nm, respectively. The turbidity measurement clearly indicated that the vincristine liposomes coated with higher concentration of CHP (CHP-CL2) are more stable than the liposomes coated with low concentration of CHP (CHP-CL1). The in vitro release of the encapsulated vincristine was carried out in phosphate buffered saline, pH 7.4. In phosphate buffered saline, the liposomes coated with higher concentration of CHP (CHP-CL2) released the drug for prolonged period of time compared to the CHP-CL1 liposomes. These experiments demonstrated that the CHP-could be synthesized in a shorter reaction time and the vincristine liposomes coated with PC/CHP weight ratio of 3:1 could be the optimum concentration to achieve the more stable liposomes. These CHP coated liposomes are ideal carriers for the targeted delivery. of therapeutic molecules. (C) 2003 Elsevier Science Lid. All rights reserved.