Evaluation of free and liposome-encapsulated gentamycin for intramuscular sustained release in rabbits

Abstract

Gentamycin sulphate ( GS) and gentamycin oleate ( GO) were encapsulated in liposomes composed of phosphatidylcholine ( HPC) and cholesterol ( CHOL) (molar ratio 7:7:2 and 5:5:l, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg −1 of GS i.v., 3 mg kg −1 of GS i.m., 3 mg kg −1 of liposome-containing gentamycin sulphate ( LGS) i.m., 3 mg kg −1 of GO i.m., and 3 mg kg −1 of liposome-containing gentamycin oleate ( LGO) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of GS; the peak plasma concentration ( C max) showed an eight-fold decrease with LGS, and the area under the concentration-time curve ( AUC) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of LGS showed a three-fold increase compared with values calculated for free GS. After the administration of the same dose of LGO, C max obtained showed a 2·5-fold decrease in relation to peak concentrations of free GO, and the apparent β-half life of encapsulated GO showed a three-fold increase compared with i.m. GO. Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.