The objective of the present work was to investigate the effect of chitosan concentration and lipid type on the characteristics of chitosan-coated liposomes and their interactions with leuprolide. Liposomes from lipid of high purity and low purity were prepared and coated by chitosan. Physical properties, drug entrapment efficiency, and stability upon dilution were respectively compared. Results showed that the particle size increment of liposomes from low purity lipid was larger than that from high purity lipid, indicating a thicker coating layer. The high zeta potential of particles from low purity lipid was thought to play an important role in the resistance to flocculation. As to particles from high purity lipid, polymer bridging caused flocculation at low polymer concentration while at high concentration, the adsorbed chitosan molecule led to steric stabilization. Drug entrapment efficiency decreased as chitosan was added to liposomes, showing the disturbance of bilayers. Upon dilution, the leakage of leuprolide from low purity liposomes was larger than that from high purity liposomes. In conclusion, low purity lipid possessed more negative charge and formed thicker adsorptive layer by stronger electrostatic attraction with chitosan. The interaction between chitosan and the polar head groups on the surface of phospholipid bilayers may interfere with leuprolide entrapped in liposomes and result in the leakage of leuprolide.

The purpose of the study was to investigate the absorption behavior of lecithin vesicles of cyclosporin A (CsA-VES), prepared by the rotary evaporation method and treated further with sonication. The everted gut sac technique and in situ circulation method were used to examine: (1) relationship between the CsA-VES absorption velocity and the CsA-VES content; (2) the influence of the intestinal mucus, blank vesicles, concentration of Na+, energy inhibitor and P-gp inhibitor on the absorption of CsA-VES; and (3) the respective accumulated content of CsA in the incubating medium and the sacs after incubation with Sandimmum Neoral

AIM: To evaluate the hypoglycemic efficacy of insulin liposomes coated by chitosan with different molecular weights and concentrations after oral administration in mice. METHODS: Insulin-liposomes were prepared by reversed-phase evaporation. Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan solution. The hypoglycemic efficacies of chitosan-coated insulin liposomes were investigated by monitoring the blood glucose level using the glucose oxidase method after oral administration to healthy mice. RESULTS: In all the insulin liposomes, the insulin liposomes coated by 0.2% chitosan (Mr 1000 kDa) showed a better hypoglycemic efficacy as compared with the other liposomes coated by chitosan. The minimum blood glucose level was 15.1%

The purpose of this study was to investigate the transport mechanisms and causes of low bioavailability of leuprolide. The everted gut sac technique and Caco-2 cell monolayer were used to examine: (1) transport properties, enzyme degradation and apparent permeation coefficient (Papp); (2) the influence of trypsin inhibitor, EDTA, chitosan and alginate on drug transport; and (3) the effect of animal species on the intestinal transport. Results showed flux increased with increasing concentration of drug, showing a passive diffusion pathway. The enzyme degradation in rabbit gut was the highest. The Papp of (4.19±1.33)×10-5cm/s in rat gut was the largest and the Papp of (5.20±0.20)×10−7cm/s in Caco-2 cell the smallest. At a low concentration of drug, trypsin inhibitor had strong enhancement effect on the Papp by protecting enough drug for permeation. Chitosan had no effect on the activity of α-chymotrypsin. The increase in Papp was due to opening of the tight junctions and interaction with cells. In conclusion, both inhibition of proteolytic enzymes and opening the tight junctions to allow for paracellular transport improved the intestinal absorption. At low drug concentration, reduction of enzyme degradation is the most important factor.

目的：制备灯盏花素脂质体并测定其包封率等理化性质。方法：采用薄膜蒸发法和冷冻干燥法制备灯盏花素脂质体。冻干品水合后，RP-HPLC法测定脂质体含量；并用透析法结合紫外分光光度法测定其包封率；利用马尔文测定仪测定脂质体的粒径、Zeta电位；并考查脂质体胶体溶液在0.9%氯化钠注射液中的释放度。结果：脂质体的载药量为20.%±0.88% （n=3），包封率为81.1%±1.1%（n=3）；冻干脂质体再分散后的粒径为50±12nm（n=3），Zeta电位为-24±9mV（n=3）；脂质体胶体溶液在氯化钠注射液中2h的释放度为17.2%±0.8%（n=3），8h的释放度为26.1%±0.7%（n=3），24h的释放度为29.9%±0.8%（n=3）。结论：灯盏花素脂质体的载药量和包封率较高，粒径在纳米大小范围，可望实现体内的长循环和靶向给药。