Ciprofloxacin Hydrochloride Liposome Research

In this paper, a novel procedure to load the fluoroquinolone antibiotic ciprofloxacinHCl (CPLX) into liposomes was described, and the influence of PEG on the stability in vitro and distribution in vivo of ciprofloxaciwHCl liposomes (CPLXL) was investigated. A method for the determination of entrapment efficiency of CPLXL (E%) by cation exchange resin - first order derivative spectrophotometry was established, which could eliminate the interference of phosphatidyl choline (PC). According to the E%, various preparative technologies were brought into comparison, and a novel method - transmembrane ammonium sulfate gradients was adopted. To obtain a optimal formulation, the influence of incubated temperature, incubated time, animonium sulfate concentration and drug-to-lipid ratio on the E% of CPLXL was assessed, and a highest E% of 94.9% was acquired. Methods for the determination of the leakage of CPLXL in saline and plasma in vitro by UV-spectrophotometry and cation exchange resin - fluorospectrophotometry were established. The leakage, stability and physiochemical characterizations were compared between CPLXL and PEG- CPLXL. It was indicated that PEG-coating enhanced the storage stability of CPLXL, reduced the particle size from I 3Orim to 3Omn and decreased the release of CPLX from liposomes in vitro. The pharmacological experiment results indicated that CPLXL and PEG- CPLXL had no irritation, and the most tolerant doses of the two liposomes were all more than 400mg/kg. After iv administration of CPLX solution, CPLXL and PEG-CPLXL, the -2- drug concentrations in different tissues were monitored with flurospectrometer. The pharmacodynamic progresses in the mice for the three preparations were brought into comparison, which showed they were all of open-type 2 compartment model, their eliminative half-life was 2.61, 9.83, 35.56h; AUC (0梮) were 9522.70, 45511.29, 55225.95 (nglml)h, respectively. The levels of CPLX of serum, spleen, lung, kidney, liver were much higher when CPLX was administrated in liposome or pegylated liposome, compared to CPLX solution.