| Liposome, as a kind of new preparation, has the traits of cellular affinity and histocompatibility, is proved to be potential in organ-targeting and delaying release which may result in the degradation of drug toxicity and elevation of stability. In order to improve the bioavailability and lessen the drug toxicity, this work was devoted to research and develop CyA liposomes, explored the regular pattern of its premeation on rats'intestinal membrane in vitro and selected the best absorption enhancer and absorption site.Agitation speed, water-oil phase volume ratio and drug-lipid mass ratio were investigated by using particle diameter as index. Orthogonal design experiments were performed to optimize the conditions for the process.The ultracentrifugation method was developed to separate the free drug from CyA liposome, and the drug content, the entrapment efficiency of liposome were determined by HPLC method we established.The physicochemcial properties of CyA liposomes were studied. The surface morphology and particle size distributions of the CyA were examined by transmission electron microscopy and laser diffraction, respectively. The results showed that the CyA liposomes prepared in our experiment were regular round-shaped and well-distributed with mean diameter of 80.41±3.12nm and polydispersity index of 0.211±0.034. The pH value of CyA-Lip was 6.5 and the encapsulation efficiency was up to (87.09±0.03)%. The visosity of CyA liposome was 2.511m Pa S; the peroxide value was 0.015.The release behavior and biodegradable characteristics of the CyA liposomes were studied with dialysis method and ultracentrifugation in vitro to explore the mechanism of release property. Results showed ultracentrifugation was more creditable to reflect the release behavior. There is an initial burst effect followed by a slower rate stage. The slower release was resulted from CyA's diffusion from the matrix and the degradation of lipid bilayer, among which the latter had a significant influence on it. However, the slow degradation of the lipid bilayer led to sustained release of CyA from the liposome.Appearance, particle diameter, entrapment efficience, pH value and peroxide value were employed as indexs to consider the influencing facters and lay up stability of this colloid disperse system. The results indicated that the CyA liposomes should be tightly preserved from light and stored at low temperature.Franz chamber perfusion technique was utilized in this investigation to explore the intestinal mucous membrane absorption of CyA-Lip. The analyte concentrations remaining in the receptor chamber sample were quantitated by a HPLC method. The effects of different intestinal segments, preparations, absorption enhancers on intestinal mucous membrane absorption of CyA were studied. The same enhanced efficiencies tendency of various enhancers in vitro permeation experiments was observed and the order were shown as follows: 1%SDCh>1%SDS>1%Sodium caprylate>1%Poloxamer F68>1%HP -β- CD.The absorption enhancers'efficiencies of CyA's permeation on membrane displayed evident segments selectivity. Colon had the highest ER value and ileum showed the best permeation effciency. The order of ER of different enhancers were: ileum> colon > jejunum≈duodenum, and the order of appearance permeation coefficient was: ileum> duodenum> jejunum> colon.After oral administrated Neoral and CyA liposome to rats, respectively, the drug concentration in different time were monitored by HPLC. The pharmacokinetics peocesses in rat for the two preparations were both accorded with two compartmental models. Their eliminative half-life was 26.54h and 27.05h individually. AUC1-72h were 46.86 and 62.95(μg/mL)·h-1, separately.
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