Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium

摘要

The aim of the present study was to design a depot delivery system of acyclovir sodium using multivesicular liposomes (MVLs) to overcome the limitations of conventional therapies and to investigate its in vivo effectiveness for sustained delivery. MVLs of acyclovir were prepared by the reverse phase evaporation method. The loading efficiency of the MVLs (45%–82%) was found to be 3 to 6 times higher than conventional multilamellar vesicles (MLVs). The in vitro release of acyclovir from MVL formulations was found to be in a sustained manner and only 70% of drug was released in 96 hours, whereas conventional MLVs released 80% of drug in 16 hours. Following intradermal administration to Wistar rats, the MVL formulations showed effective plasma concentration for 48 hours compared with MLVs and free drug solution (12–16 hours). Cmax values of MVL formulations were significantly less (8.6–11.4 μg/mL) than MLV and free drug solution (12.5 μg/mL). The AUC0–48 of the MVL formulations was 1.5- and 3-fold higher compared with conventional liposomes and free drug solution, respectively. Overall, formulations containing phosphatidyl glycerol as negatively charged lipid showed better results. The MVL delivery system as an intradermal depot offers the advantage of a very high loading and controlled release of acyclovir for an extended period of time. The increase in AUC and decrease in Cmax reflects that the MVL formulations could reduce the toxic complications and limitations of conventional IV and oral therapies.