A Research Of Controllable Preparation And Drug-loading Of A New Type Of Liposome

Liposomes are novel drug carriers, as they have good biocompatibility, biodegradability, innocuity, non-immunogenicity. As a drug carrier, they can elevate the therapeutic exponent, reduce their untoward effects, and decrease the dosage of the medicine. But liposomes are less stable. During its storage, the drug may be detrayed and liposomes may be aggregated, ruptured, and so on. These may lead to not meet the demand of clinical medication. Based on these problems, a novel drug carrier-liposomes-like with good stability and higher entrapment efficiency was designed by our studying team. Namely a dendritic framework structure was introduced into liposomes, which can make terminal chain segment of dendritic branch incorporate phospholipid bilayers and perform a vesicle similar to liposomes. The appearance of dendrimer provides realistic feasibility for the design. In order to introduce the dendritic framework structure into liposomes effectively, the terminal chain segment of dendrimer should be modified hydrophobically. PAMAM Dendrimer G3.5 was choosed, the carboxyls on terminal chain segment were activated with DCC and NHS, then the coupling reactionwere with stearylamine was formed via active ester. Finally the lipid globule of PAMAM dendrimer G3.5 were prepared successfully. We prepared the liposomes-like using hydrogenated soybean lecithin, cholesterol and the lipid globule of PAMAM dendrimer G3.5 by film dispersed method (TFDM) successfully. The optimization of the new type podophyllotoxin liposome preparation was performed based on the orthogonal experimental design. In this study, the size of the new type podophyllotoxin liposome were taken as the index and the influence of factors such as the proportion of hydrogenated phospholipid and Cholesterol, the proportion of hydrogenated phospholipid and PAMAM dendrimer G3.5 lipid globule, the temperature of rotary evaporation and the temperature of hydration. We prepared drug-loaded liposomes-like with Podophyllotoxin as a model drug. The shape of liposomes were observed by transmission electron microscopy (TEM), and the particles size was evaluated by dynamic scattering (DLS). The entrapment efficiency was determined using dextran gel column separation. The optimization of the new type podophyllotoxin liposome preparation was performed based on the orthogonal experimental design. In this study, the entrapment efficiency of the new type podophyllotoxin liposome were taken as the index and the influence of factors such as the proportion of hydrogenated phospholipid and Cholesterol, the proportion of hydrogenated phospholipid and PAMAM dendrimer G3.5 lipid globule, the proportion of hydrogenated phospholipid and podophyllotoxin and the temperature of rotary evaporation. Tolerance to temparature, ethanol and acid-base were studied, too. And vitro percutaneous permeability was studied. We also studied the Quality Standards inspection of the new type podophyllotoxin liposome. The results showed that the best formulation of the new type podophyllotoxin liposome were the proportion of hydrogenated phospholipid and Cholesterol was 20:3.26, the proportion of hydrogenated phospholipid and PAMAM dendrimer G3.5 lipid globule was 20: 0.5, the temperature of rotary evaporation was 55℃and the temperature of hydration was 45℃. And liposomes-like were successfully prepared with an average diameter of 61.1 run. The best formulation of the new type podophyllotoxin liposome were the proportion of hydrogenated phospholipid and Cholesterol was 20:3.67, the proportion of hydrogenated phospholipid and PAMAM dendrimer G3.5 lipid globule was 20:0.5, the proportion of hydrogenated phospholipid and podophyllotoxin was 20:1.5 and the temperature of rotary evaporation was 45℃. And the encapsulation efficiency was 91.45%. Curcumin liposomes-like were tolerant of steam sterilization (115℃,67kPa,30min),50% ethanol (final concentration),1M Hydrochloride (final concentration) and 0.1M NaOH (final concentration). In vitro percutaneous permeability study, it achieved the sustained-release effect of the drug release. In the podophyllotoxin content and distribution are more ideal in terms of uniformity. Conclusion demonstrated that liposomes-like have higher entrapment efficiency and better stability than traditional liposomes, and make the loaded drug play its role better.