目的 确立分光光度法判断脂质体相对大小，为评估脂质体物理稳定性提供一种简便、快捷的方法。方法 以Rayleigh-Gans-Debye理论为基础，固定脂质体膜材的种类、比例及其在溶液中的总量，分别用乙醇注入法和高压乳匀法制备不同粒径的空间稳定脂质体，以电镜法和热力学光散射法测得的粒径作为标准，找出不同方法制得脂质体在436nm波长处的吸光度A与粒径D的关系。结果 单位磷脂浓度的脂质体溶液在436nm 处log（A436nm PCp）与脂质体粒径的对数logD呈线性相关（r2≥E0.93，n=5）。结论 脂质体溶液的吸光度能反映脂质体相对大小，可作为一种评定脂质体物理稳定性的方法。

在传代培养的HeLa细胞上观察了叶酸对脂质体靶向摄取功能的影响。将内含钙黄绿素的叶酸-脂质体和脂质体分别加入HeLa细胞中培养，并以荧光法检测细胞摄取量。共同培养4h，细胞摄取叶酸-脂质体量为脂质体4倍以上，在0.45mg·mL.1时达饱和；过量游离叶酸竞争抑制细胞对叶酸-脂质体的摄取；磷脂酶D或磷脂酰肌醇特导性磷脂酶C通过影响叶酸受体而抑制细胞对叶酸-脂质体的摄取。因此，HeLa细胞主要通过叶酸受体途径介导摄取叶酸-脂质体；叶酸受体高表达或高活性细胞摄取叶酸-脂质体的能力较未接叶酸的脂质体显著提高。

目的 研制一种能通过叶酸受体途径靶向肿瘤细胞的叶酸O脂质体。方法 将叶酸（F）、聚乙二醇二胺（NH2 -PEG-NH2）、琥珀酸酐（SUC）和卵黄磷脂酰乙醇胺（EPE）按序共价连接，并与胆固醇（chol）、卵黄磷脂酰胆碱（EPC）以10∶40∶56 配比，用成膜-水化结合冷冻-熔融超声法制备内含钙黄绿素叶酸-脂质体，以负染色-电镜法确定其粒径；用荧光显微镜观察HeLa细胞摄取叶酸-脂质体与脂质体的差异；以荧光定量法确定浓度、时间、游离F、磷脂酶D（PLD）和磷脂酰肌醇特异磷脂酶C（PIPLC）对HeLa细胞摄取叶酸-脂质体影响程度。结果 （1）F-PEG-SUC-EPE连接物为色谱纯；叶酸-脂质体平均粒径为200nm。（2）叶酸-脂质体进入HeLa细胞质内量明显高于脂质体。（3）浓度增大、时间延长，叶酸-脂质体摄取量递增幅度明显减缓；HeLa细胞摄取叶酸-脂质体量均在脂质体的4倍以上。（4）50μmol/L游离F可使叶酸-脂质体摄取量降低50%； PIPLC（0.2U/ml）和PLD（0.5mg/ml）处理后，叶酸-脂质体摄取量分别降低71%和70%。结论 200nm 粒径的叶酸-脂质体能通过细胞膜上F受体介导内吞入胞，并能显著靶向富集F受体的肿瘤细胞。

目的：研制一种具有较好生物粘附能力和药物缓释效果的阿昔洛韦（Acv）-卡波姆（Cb）-乙基纤维素（Ec）微球。方法：通过油包水乳剂的溶媒蒸发法制备Acv-Cb-Ec微球；以动物体内外胃粘膜表面滞留程度，考察Cb与Ec不同配比、Acv含量、微球粒径对Acv-Cb-Ec微球生物粘附能力的影响；以体外释药速率评价Cb与Ec不同配比、Acv含量、微球粒径和介质pH对Acv-Cb-Ec微球缓释效果影响。结果：Cb配比增加，Acv2Cb2Ec微球生物粘附能力增强，药物缓释效果降低，表现为负相关性；Acv含量增加，Acv-Cb-Ec微球生物粘附能力和药物缓释效果均降低，但Acv含量≤20%时，缓释效果基本接近；粒径增大，Acv-Cb-Ec微球生物粘附能力有所减小，但在500～1200μm时，药物缓释效果显著提高（12h），而粘附性变化不明；Acv-Cb-Ec微球在酸性介质中的释药速率明显快于中性或近中性介质。结论：载药量≤20%，粒径为500～1200μm，Cb与Ec配比为1∶9 的Acv-Cb-Ec微球在胃粘膜表面具有良好粘附特性，且药物缓释可达12h，近中性pH条件下的缓释效果更佳。

Liposome and PG kit were labeledwithg the 99m TcO4 to form 99m Tc-liposome and 99m Tc-PG which are two non-invasive, safe diagnostic drugs. The labeling efficiency of the agents are more than 95%. The 99m imaging agents in the PLN as compared with the other different organs showed that the ratio value of PLN to other organ ismore than 149 times after 30 min i.d. injection of 99m Tc-liposome and the ratio value is more than 30.19 times after 2h. i.d. injection of 99m Tc-PG. The studies of the pharmacokinetics and mechanism of imaging have been carried out. The 99m Tc-liposome was administrated to more than 140 patients and 99m Tc-PG was administratedto more than 5000 patients. The clinical tests were satisfactory and no side-effect was shown.

The chromatographic analysis of polyethylene glycols (PEG) and their amino-substituted derivatives, with an average molecular mass of 2000 and 3350 is described. The PEG derivatives were perfectly separated by TSK-GEL G4000PWXL column, which was widely used in high-performance size-exclusion chromatography (SEC), at low ionic strength with refractive index detection. It was shown that ion-exchange interactions were mainly involved in the retention mechanism of these compounds on TSK-GEL G4000PWXL column, since retention volume decreased when salt concentration were added to the mobile phase and varied with the pH of the eluent. Additionally, size exclusion for PEG chains plays a role. Organic modifiers also had effect on chromatographic behaviors of PEG compounds.

Amoxicillin mucoadhesive microspheres (Amo-ad-ms) were prepared using ethylcellulose (Ec) as matrix and carbopol 934P as mucoadhesive polymer for the potential use of treating gastric and duodenal ulcers, which were associated with Helicobacter pylori. The morphological characteristics of the mucoadhesive microspheres were studied under scanning electron microscope. In vitro release test showed that amoxicillin released faster in pH 1.0 hydrochloric acid (HCl) than in pH 7.8 phosphate buffer. Yet, it would be degraded to some extent in a pH 1.0 HCl medium at 37 8C, which indicated that amoxicillin was not stable in an acidic surrounding. It was also found that amoxicillin entrapped within the microspheres could keep stable. In vitro and in vivo mucoadhesive tests showed that Amo-ad-ms adhered more strongly to gastric mucous layer than nonadhesive amoxicillin microspheres (Amo-Ec-ms) did and could retain in gastrointestinal tract for an extended period of time. Amo-ad-ms and amoxicillin powder were orally administered to rats. The amoxicillin concentration in gastric tissue was higher in the Amo-adms group. In vivo H. pylori clearance tests were also carried out by administering, respectively, Amo-ad-ms or amoxicillin powder, to H. pylori infectious BALB/c mice under fed conditions at single or multiple dose(s) in oral administration. The results showed that Amo-ad-ms had a better clearance effect than amoxicillin powder did. In conclusion, the prolonged gastrointestinal residence time and enhanced amoxicillin stability resulting from the mucoadhesive microspheres of amoxicillin might make contribution to H. pylori clearance.

Eglin c from the leech Hirudo medicinalis is a potent protein inhibitor of many serine proteinases including chymotrypsin and subtilisins. Unlike most small protein inhibitors whose solvent-exposed enzymebinding loop is stabilized primarily by disulfide bridges flanking the reactive-site peptide bond, eglin c possesses an enzyme-binding loop supported predominantly by extensive electrostatic/H-bonding interactions involving three Arg residues (Arg48, Arg51, and Arg53) projecting from the scaffold of the inhibitor. As an adjacent residue, the C-terminal Gly70 participates in these interactions via its R-carboxyl group interacting with the side chain of Arg51 and the main chain of Arg48. In addition, the amide NH group of Gly70 donates an H-bond to the carbonyl CdO groups of Arg48 and Arg51. To understand the structural and functional relevance of the electrostatic/H-bonding network, we chemically synthesized wild-type eglin c and three analogues in which Gly70 was either deleted or replaced by glycine amide (NH2CH2CONH2) or by R-hydroxylacetamide (HOCH2CONH2). NMR analysis indicated that the core structure of eglin c was maintained in the analogues, but that the binding loop was significantly perturbed. It was found that deletion or replacement of Gly70 destabilized eglin c by an average of 2.7 kcal/mol or 20℃ in melting temperature. As a result, these inhibitors become substrates for their target enzymes. Binding assays on these analogues with a atalytically incompetent subtilisin BPN' mutant indicated that loss or weakening of the interactions involving the carboxylate of Gly70 caused a decrease in binding by approximately 2 orders of magnitude. Notably, for all four synthetic inhibitors, the relative free energy changes (△△G) associated with protein destabilization are strongly correlated (slope=0.94, r2=0.9996) with the △△G values derived from a decreased binding to the enzyme.

采用两步反应法制备脂质体空间稳定膜材料甲氧基聚乙二醇-磷脂酰乙醇胺（MPEG-EPE），度用以制备空间稳定脂质体（SLs），同时制备不含MPEG-EPE的传统脂质体（CLs），比较两者放置过程中粒径变化、加乙醇后浊度变化、包封钙黄绿素后的在冻干再水化过程中的荧光泄露程度及其与人血浆蛋白的吸附指标，评价MPEG2000-EPE对脂质体的稳定作用。结果表明，试验前后SLs的粒径及浊度变化不大，荧光泄露程度和人血浆蛋白吸附量也远小于CLs，提示其对脂质体有良好的稳定作用。

目的 探讨阿霉素不同盐型对脂质体的体内外稳定性的影响。方法 以薄膜分散-挤压法制备含有不同缓冲对的空白脂质体，用pH 梯度和化学梯度法包载阿霉素，对其在脂质体内状态进行观察，测定了阿霉素脂质体理化性质；用透析法检测阿霉素脂质体在不同介质中的药物泄漏；用HPLC法研究不同盐型阿霉素脂质体在大鼠体内药动学行为。结果 甘氨酸盐缓冲液、柠檬酸盐缓冲液和硫酸铵溶液作内水相制得的空白脂质体的平均粒径分别为103.3±7.6nm、101.9±11.7nm 和97.3±8.4nm，Zeta 电位分别为-21.3±0.5mv、-21.7±0.4mv、-20.9±0.7mv，对阿霉素的包封率分别为47.8%、96.7%、98.6%；甘氨酸盐制得的脂质体体外泄漏最快，硫酸铵制得的脂质体泄漏最慢；甘氨酸盐缓冲液、柠檬酸盐缓冲液和硫酸铵溶液作内水相制得的阿霉素脂质体大鼠体内平均滞留时间分别为12.13h、23.31h 和29.79h。结论 阿霉素在脂质体内水相中不同盐型影响其脂质体的体内外稳定性，以硫酸铵为内水相制得的阿霉素脂质体最稳定，其稳定次序与内水相中酸的强度有关，酸性越弱的其脂质体稳定性越高