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。

目的 研究酪蛋白和鱼精蛋白对酶降解胰岛素（INS）的保护作用及对大鼠灌胃给予INS溶液和微球后降血糖作用的影响。方法 采用：HPI止法测定α-糜蛋白酶和胰蛋白酶溶液中INS的残余量+考察酪蛋白和鱼精蛋白对体外酶陴解INS的保护作用；制各INS溶液及肠溶傲球。在促吸荆N-[8-（2-羟基苯甲酰幕）氮基]辛酸钠（SNAC）存在下，太鼠灌胃给药研究酷蛋白和鱼精蛋白单独腰合并使用对INS溶液和徽球降血糖作用的影响。结果 酪蛋白对α-糜蛋白酶体外降解INS有较好的抑制作用，鱼精蛋白不能抑制α-靡蛋白酶对INS的降解，但对胰蛋白酶降解INS的抑制作用忧于酪蛋白。鱼精蛋白和酪蛋白均可增加I№溶液和肠溶微球的降血糖作用，两者台用嫂果更佳。在SNAC、鱼精蛋白和酪蛋白存在下。INS肠溶豫球比INS籍液有更强而持久的降血糖作用。结论 酪蛋白和鱼精蛋白可通过竞争性与酶结音机制增加INS在肠道消化酶中的稳定性。对INS口服吸收有利。

目的：制备新型的两亲性N-辛基-N-PEG化壳聚糖衍生物。方法：以天然聚合物壳聚糖为原料，其2-NH-与辛醛形成Schiff's碱，用KBH4还原得到N-辛基壳聚糖，然后在其剩余2-NH-与MeO-PEG-CHO反应，再用KBH4还原制备了N-辛基-N-PEG化壳聚糖衍生物，结构经FTIR、13CNMR、1HNMR得到了表征。用DSC实验对其物理性质进行了分析。结果与结论：制得了新型的辛基、PEG取代度分别为36，64%的两亲性N-辛基-N-PEG化壳聚糖衍生物，有望作为难溶性药物增溶的载体。

The aim of this study was to design and characterize lectin-modified liposomes containing insulin and to evaluate the potential of these modified colloidal carriers for oral administration of peptide and protein drugs. Wheat germ agglutinin (WGA), tomato lectin (TL), or Ulex europaeus agglutinin 1 (UEA1) were conjugated by coupling their amino groups to carbodiimideactivated carboxylic groups of N-glutaryl-phosphatidylethanolamine (N-glut-PE). Insulin liposomes dispersions were prepared by the reverse-phase evaporation technique and modified with the lectin-N-glut-PE conjugates. Lectin-modified liposomes were characterized according to particles size, zeta potential and entrapment efficiency. The hypoglycemic effect indicated by pharmacological bioavailability of insulin liposomes modified with WGA, TL and UEA1 were 21.40, 16.71 and 8.38% in diabetic mice as comparison with abdominal cavity injection of insulin, respectively. After oral administration of the insulin liposomes modified with WGA, TL and UEA1 to rats, the relative pharmacological bioavailabilities were 8.47, 7.29 and 4.85%, the relative bioavailability were 9.12, 7.89 and 5.37% in comparison with subcutaneous injection of insulin, respectively. In the two cases, no remarkable hypoglycemic effects were observed with the conventional insulin liposomes. These results confirmed that lectin-modified liposomes promote the oral absorption of insulin due to the specific-site combination on GI cell membrane.