Primary Studies On Preparation And Pharmacology Of Liposomal Amikacinsulfate

The main shortcoming of the traditional preparation of amikacinsulfate is its short elimination half-life ,great consumption and toxicity of ear , kidney and neural muscle. Liposomal amikacinsulfate can improve above-mentioned index. On the basis of evaluating separately the influence of several factors on the encapsulation efficiency and stability ,the orthogonal design was utilized to optimize the preparation and formulation of liposomal amikacinsulfate. The results showed that the ideal ratio for lecithinxholesterol is 1.5:1, the ratio for amikacinsulfate :(lecithin+cholesterol) is 1:15 and pH of PBS is 7.0, the ratio for organic solvent PBS is 3:1. The encapsulation efficiency is 64.8%,and its stability is satisfying.The experiment was conducted in rabbit s body to investigate pharmacokinetics about liposomal amikacinsulfate. A dose of 12.5mg/kg.bw liposomal amikacinsulfate was given iv to rabbits and blood samples were collected at different time during 24 hours to measure the drug concentration. The results showed that drug concentration-time curve conformed to one compartment-open model. Its main pharmacokinetical parameters were t_1/27.40 h, Vd 39.46 mL, AUC 6899.51 h.μg/mL, ClB3.82mL/h.Acute toxicity of liposomal amikacinsulfate in mice showed maximum tolerance capacity of liposomal amikacinsulfate was higher than 750 mg/kg. bw. 80 mice were randomly divided into 4 groups .140,70,35,0 mg/kg.bw liposomal amikacinsulfate were supplied to each group by i.p for 4 weeks in succession in order to investigate its subchronic toxicity . The results indicated that toxicity of liposomal amikacinsulfate was significantly lower than that of conventional amikacinsulfate.Liposomal amikacinsulfate,was compared its MIC and MBC against E.coli, streptococcus, pasteurella multocid and staphylococcus aureus with free amikacinsulfate in order to study its antibacterial effect in vitro .The MIC of liposomal amikacinsulfate against the bacterias mentioned above were 1/3.5,1/7,1/2,1/2 of that of free amikacinsulfate, and the MBC were 1/4,1/4,1/1.8,1/4 of it. The results showed the antibacterial effect of liposomal amikacinsulfate was superior to free amikacinsulfate.In order to study clinical application of liposomal amikacinsulfate, A pig farm infected with streptococcosis suis was sellected to conducte clinical trail compared with conventional amikacinsulfate. 216 pigs were divided into five goups. Pigs of the...