白细胞介素—2脂质体的抗肿瘤作用试验

本文建立Ｃ５７ＢＬ／６小鼠荷瘤动物模型，通过给荷瘤小鼠腹腔注射空白脂质体、单纯ＩＬ－２及ＩＬ－２脂质体来比较其在肿瘤生长中的抑制作用。结果是空白脂质体组抑瘤率为４．２６％，单纯ＩＬ－２和脂质体ＩＬ－２的抑瘤率分别为３４．０４％和５４．６０％。空白脂质体组与单纯对照组相比无显著性差异（Ｐ＞０．０５），脂质体ＩＬ－２组与单纯ＩＬ－２组之间存在显著性差异（Ｐ＜０．０５），脂质体ＩＬ－２的抑瘤率比单纯ＩＬ－２抑瘤率提高了２０．６％。     

MDP-阿霉素脂质体交联物治疗大鼠成骨肉瘤的药效学研究

目的：制备出MDP－阿霉素脂质体交联物（MDP－LADM），观察MDP－LADM治疗大鼠成骨肉瘤UMR106模型伯疗效，并与游离阿霉素（ADM）及阿霉素脂质体（LADM）作比较。方法：建立SD大鼠UMR106成骨肉瘤模型，将磷脂修饰后用1，4，－二异氰基甲苯酯（TDD与MDP交联，用改良的逆向蒸发将其制备成阿霉素脂质体－MDP交联物。将荷瘤大鼠随机分为五组，即生理盐水组，ADM组，游离ADM＋空白脂质体组，LADM组及MDP－LADM组，观察它们对大鼠的抑瘤作用。用高效液相色谱测定阿霉素在骨组织及其它器官中的含量。结果：MDP－阿霉素脂质体交联物对阿霉素包裹率为92．3％，MDP交联率为70．2％，对SD大鼠UMR106成骨肉瘤模型的抑瘤作用明显高于阿霉素（P＜0．01）和阿霉素脂质体（P＜0．05），治疗后大鼠生存期明显延长（P＜0．01），阿霉素在骨组织中的含量明显增加。结论：MDP－阿霉素脂质体交联物可明显提高阿霉素脂质体对骨肿瘤的治疗作用，降低其不良反应。     

a干扰素治疗慢性乙肝不良反应的观察及护理

目的：观察a干扰素治疗慢性乙肝不良反应及对其护理对于治疗依从性的影响。方法：慢性乙肝患者160例随机分为观察组和对照组，给予a干扰素治疗，分别观察所出现的不良反应，观察组进行以心理护理为主的针对性护理，对照组单纯对症治疗。结果：不良反应发生率，观察组为92．77％，对照组为93．51％，差异无显著性意义（P〉0．05）；观察组依从率95．18％显著高于对照组84．42％，差异有显著性意义（P〈0．05）。     

宫颈电环切除术前后肿瘤坏死因子α及白细胞介素2的变化及意义

目的探讨宫颈电环切除术（LEEP）前后肿瘤坏死因子α（TNF-α）及白细胞介素2（IL-2）等细胞因子的变化及意义。方法采用酶联免疫吸附法（ELISA）测定高危人乳头瘤病毒（HPV）感染的宫颈上皮内瘤变I级（CINI）30例、Ⅱ级（CINII）30例、Ⅲ级（CINⅢ）27例患者LEEP手术前后宫颈局部TNF—α及IL-2的水平。并与25例非HPV感染正常宫颈组织（NCE）相比较。结果LEEP手术前CINI组中TNF-α及IL-2水平与对照组比较．差异无统计学意义（P〉0．05）;LEEP手术前CINⅡ、CINⅢ组中TNF—α及IL-2水平均高于对照组,差异有统计学意义（P〈0．05）;手术后均下降,与手术前比较,差异有统计学意义（P〈0．05）;CINⅡ组手术后TNF-α、IL-2水平及CINⅢ组手术后IL-2水平与对照组比较,差异无统计学意义（P〉0．05）;CINⅢ组手术后TNF-α水平高于对照组,差异有统计学意义（P〈0．05）。CINI、CINⅡ、CINⅢ组HPV病毒转阴率分别为100．0％、93．3％、96．3％,总转阴率为96．6％。结论高危HPV感染的宫颈高度病变中宫颈局部可能存在免疫失衡,LEEP术后免疫失衡有所改善,手术对宫颈局部TNF-α及IL-2水平的影响有限,仍需大样本、多因素的长期追踪。     

爱迪注射液配合化疗治疗晚期结肠癌疗效及免疫功能变化的观察

目的比较爱迪注射液配合化疗（治疗组）与单纯化疗（对照组）对晚期结肠癌的疗效、生活质量及免疫功能的影响。方法62例晚期结肠癌患者随机分为爱迪注射液配合化疗组（治疗组）与单纯化疗组（对照组），连续治疗4周，并比较两组间疗效、生活质量及免疫功能。结果有效率治疗组43．7％，对照组33．3％，两组比较差异无显著性（P〉0．05）。治疗组生活质量评分治疗组高于对照组，两组间差异有显著性（P〈0．05）。治疗组治疗前后毒性反应、免疫功能改变明显低于对照组，差异有显著性（P〈0．05）。结论爱迪注射液与化疗联用治疗晚期结肠癌，可降低化疗对患者免疫功能的影响及毒副反应，改善患者的生活质量。     

叶酸结合根除Hp对慢性萎缩性胃炎转归的影响

目的探讨叶酸（FA）对慢性萎缩性胃炎（CAG）的影响。方法将30例慢性萎缩性胃炎患者随机分为治疗组（口服叶酸连续3个月，加奥美拉唑、克拉霉素、灭滴灵治疗1周）和对照组（仅用奥美拉唑、克拉霉素、灭滴灵治疗1周），在治疗前后分别行胃镜及病理检查，观察CAG的转归。结果胃镜观察治疗后治疗组显效2例，有效4例，无效9例，总有效率40．0％，Hp转阴率93．33％；对照组显效0例，有效2例，无效13例，总有效率13．33％，Hp转阴率86．67％；治疗组总有效率明显高于对照组（X^2=5．1675。P〈0．05），而Hp转阴率两组无明显差异（X^2=0．3704，P〉0．05）。病理组织观察发现，叶酸组治疗后能明显改善CAG萎缩（P〈0．05）、肠化（P〈0．05）及炎症（P〈0．05），但对异型增生无明显影响（P〉0．05）；治疗组与对照组比较差异有显著性趋势（P值接近显著性水平）；治疗前后组织病理的萎缩与肠化改变一致（r=0．38，P〈0．05），内镜观察与病理组织学改变同步。结论叶酸结合根除Hp对CAG组织病理有改善作用。     

雷贝拉唑治疗幽门螺杆菌阳性十二指肠溃疡的临床研究

目的观察雷贝拉唑联用抗生素治疗幽门螺杆菌（HP）阳性十二指肠溃疡的临床疗效。方法将80例患者随机分为治疗组（雷贝拉唑组）40例和（奥美拉唑组）40例，并同时加用阿莫西林和甲硝唑进行治疗，停药后4周复查胃镜及HP检测。结果治疗组疼痛消失时问（1．27±0．83）d短于对照组（2．41±1．26）d，差异具有显著性（P〈0．05）；1周末、2周末的症状消失率两组分别为95．0％（38／40）、97．5％（39／40）和90．0％（36／40）、95．0％（38／40），差异无显著性（均P〉0．05）；HP根除率分别为95．O％（38／40）和92．5％（37／40）（P〉0．05）；溃疡愈合率和总有效率分别为95．0％（38／40）、97．5％（39／40）和90．1％（38／42）、95．0％（38／40），两组比较差异无显著性（P〉0．05）；治疗组不良反应8例少于对照组14例。结论雷贝拉唑有较高的溃疡愈合率和HP根除率，止痛效应快，不良反应发生率较低。     

不同麻醉方法对胃癌根治术病人围术期免疫功能的影响

目的探讨不同麻醉方法对胃癌根治术病人围术期白细胞介素-6（IL-6）、T淋巴细胞亚群及自然杀伤细胞（NK细胞）的影响。方法选择胃癌根治术病人30例，随机分为2组。Ⅰ组为单纯全麻，Ⅱ组为全麻复合硬膜外麻醉。分别于麻醉前、麻醉后2h、术后1d和6d抽取静脉血，用放免法测定血清IL-6含量，用流式细胞仪测定T淋巴细胞亚群及NK细胞的数量。结果两组麻醉后2h IL-6均明显升高，与麻醉前比较，Ⅰ组P〈0．01；Ⅱ组P〈0．05，组间比较亦有显著性差异（P〈0．05），T细胞亚群CD3^＋、CD4^＋、CD4^＋/CD8^＋、NK细胞均有所下降，与麻醉前比较，Ⅰ组P〈0．05；术后1d两组IL-6均较麻醉前升高，但无显著性差异；T细胞亚群CD3^＋、CD4^＋、CD4^＋／CD8^＋下降较明显，与麻醉前比较Ⅰ组P〈0．01，Ⅱ组P〈0．05，组间亦有显著性差异（P〈0．05）；术后6d各组数据均恢复至术前水平。麻醉后2d、术后1dCD8＋较麻醉前稍有升高，但无显著性差异。结论胃癌根治术病人麻醉手术后免疫功能有一过性不同程度的抑制，其中以单纯全麻组明显。全麻复合硬膜外麻醉组明显轻于单纯全麻组。     

三维适形放疗联合金龙胶囊治疗原发性肝癌52例疗效分析

目的探讨三维适形放疗联合金龙胶囊治疗原发性肝癌的临床疗效。方法52例原发性肝癌患者随机分为两组，单纯三维适形放疗组（对照组）和三维适形放疗联合金龙胶囊组（治疗组）各26例。观察两组治疗的近期疗效、临床受益反应率和不良反应。结果治疗组近期疗效76．9％，对照组57．6％，两组比较有显著性差异，P〈0．05；治疗组临床受益率76．9％，对照组61．6％，两组比较有显著性差异，P〈0．05。两组不良反应发生率比较，均无显著性差异，P〉0．05。结论三维适形放疗联合金龙胶囊治疗原发性肝癌安全有效，值得推广。     

中西药并用治疗慢性胃炎疗效观察

目的：观察中西药并用治疗慢性胃炎疗效。方法：将幽门螺杆菌（HP）阳性慢性胃炎患者随机分为两组。治疗组30例，西药用庆大霉素稀释后口服10d，甲氰咪胍口服2周，丽朱得乐胶囊口服4周，并给与补中益气汤加减服用10d。对照组30例，单纯西药治疗，疗程相同。结果：临床结果显示，治疗组临床症状改善痊愈率63．3％，对照组46．7％，两组间差异有显著性（P＜0．05）。胃镜检查：治疗组临床愈率53．3％，对照组36．7％，两组间差异有显著性（P＜0．05）。结论：中西药并用治疗慢性胃炎较单纯西药治疗效果明显，痊愈率高。     

Interleukin-2-Containing Liposomes: Interaction of Interleukin-2 with Liposomal Bilayers and Preliminary Studies on Application in Cancer Vaccines

Interleukin-2 (IL-2) incorporation in liposomes was studied under different conditions. Information was obtained on the mechanism of interaction of glycosylated recombinant IL-2 with liposomal bilayers. This information was utilized to formulate liposomes with high levels of incorporated IL-2. Multilamellar vesicles were prepared by hydration of a lipid film with an IL-2 solution. The incorporation efficiency, measured with a bioassay after forced release of IL-2 from the vesicles, was strongly dependent on the charge of the liposomes and the pH and ionic strength of the hydration medium. Negatively charged liposomes composed of phosphatidylcholine/ phosphatidylglycerol (9:1) and prepared with IL-2 dissolved in 10 mM NaAc/270 mM glycerol, 0.1% BSA, pH 5, showed the highest incorporation efficiency (81%) among the investigated preparations. This type of liposome was selected for further study. Electrostatics play a crucial role in the process of IL-2 association with this type of liposome. Initial studies concerning induction of protective tumor immunity by immunization with reconstituted membranes with mu-ramyl tripeptide phosphatidylethanolamine indicate that coinjection of IL-2-containing liposomes provided a significant enhancement of the immune response.     

A novel and simple type of liposome carrier for recombinant interleukin-2

The strong interaction between recombinant interleukin-2 (IL-2) and liposome was characterized and its possible application to drug-delivery control considered. The liposomes were prepared with egg phosphatidylcholine, distearoyl-phosphatidylglycerol (DSPG), dipalmitoyl-phosphatidylcholine, dipalmitoyl-phosphatidylglycerol or distearoyl-phosphatidylcholine (DSPC). Small and hydrophobic liposomes were selected, which were composed of saturated and long-fatty-acid-chain phospholipids. When the composition and the mixture ratio of IL-2 and the liposomewere optimized, morethan 95% ofthe lyophilized IL-2 (Imunace, 350000 JRU) was adsorbed consistently onto the DSPC-DSPG liposome (molar ratio, 10:1; 25 micromol mL(-1); 30 nm in size). Merely mixing IL-2 lyophilized with liposome suspension is convenient pharmaceutically. After intravenous administration to mice, liposomal IL-2 was eliminated half as slowly from the systemic circulation as free IL-2, with more than 13 and 18 times more IL-2 being delivered to the liver and spleen, respectively. After subcutaneous administration of liposomal IL-2 to mice, the mean residence time of IL-2 in the systemic circulation was 8 times that of free IL-2. These results show that IL-2 consistently adsorbs onto the surface of liposomes after optimization of its composition and mixing ratio. Intravenous and subcutaneous administration to mice demonstrates the gradual release of IL-2. Further trials are warranted using these liposomes.     

Consistent interactions between tumor cell IL-6 and macrophage TNF-α enhance the growth of human prostate cancer cells in the bone of nude mouse

To test the hypothesis that tumor-associated macrophages (TAMs) enhance the growth and metastasis of human prostate cancer in the bone, we evaluated the effects of decreasing interleukin-6 (IL-6) production by tumor cells and TAMs in a mouse model of bone metastasis. Human PC-3MM2 cells that produce IL-6 were transfected with lentivirus containing IL-6 small hairpin RNA (shRNA) or nonspecific RNA and injected into the tibias of nude mice treated intraperitoneally every 5days for 5weeks with phosphate-buffered saline (PBS), liposomes containing PBS, or liposomes containing clodronate (to decrease the number of macrophages). Transfection of PC-3MM2 cells with IL-6 shRNA significantly decreased cellular expression of IL-6 and the number of TAMs and osteoclasts in bone tumors, which correlated with significant decreases in tumor size, bone lysis, and incidence of lymph node metastasis. Treatment of mice with clodronate liposomes significantly decreased the number of TAMs and osteoclasts in the bone tumors, the expression of IL-6 in the PC3-MM2 cells, and the production of tumor necrosis factor (TNF)-α by TAMs. These findings correlated with a significant decrease in tumor size, bone lysis, and lymph node metastasis. Knocking down IL-6 in tumor cells and decreasing TAMs was associated with the lowest incidences of bone tumors and lymph node metastasis. These results suggest that TAMs enhance the growth of prostate cancer cells in the bone.     

Immunogenicity of Liposomes Containing Lipid Core Peptides and the Adjuvant Quil A

Purpose The purpose of this study was to investigate the immunogenicity of liposomes containing mannosylated lipid core peptide (manLCP) constructs, both in vitro and in vivo, with or without the addition of the immune stimulating adjuvant Quil A. Methods Mouse bone marrow dendritic cells (BMDC) were cultured with liposome formulations for 48 h, and the resulting level of BMDC activation was determined by flow cytometry. BMDC pulsed with liposome formulations were incubated with 5,6-carboxyfluoroscein diacetate succinimidyl ester-labeled T cells for 72 h and the resulting T cell proliferation was determined by flow cytometry. To investigate the immunogenicity of formulations in vivo, groups of C57Bl/6J mice were immunized by subcutaneous injection, and the resulting antigen-specific cytotoxic and protective immune responses toward tumor challenge evaluated. Results Despite being unable to demonstrate the activation of BMDC, BMDC pulsed with liposomes containing manLCP constructs were able to stimulate the proliferation of na?ve T cells in vitro. However, in vivo only liposomes containing both manLCP and Quil A were able to stimulate a strong antigen-specific cytotoxic immune response. Liposomes containing manLCP and Quil A within the same particle were able to protect against the growth of tumor cells to a similar level as if the antigen was administered in alum with CD4 help. Conclusion ManLCPs administered in liposomes are able to stimulate strong cytotoxic and protective immune responses if Quil A is also incorporated as an adjuvant.     

Interleukin-2 liposomes for primary immune deficiency using the aerosol route.

This is the first report of aerosol interleukin 2 (IL-2) liposome administration to individuals with immune deficiency. Parenteral IL-2 therapy has shown beneficial effects in some patients with cancer, common variable immunodeficiency (CVID), and human immunodeficiency virus (HIV) but is problematic because of side effects including fever and malaise as well as local swelling (delayed type hypersensitivity like reaction) after each subcutaneous IL-2 injection. Provision of an IL-2:human albumin liposome formulation via the aerosol route had few side effects in a recent clinical trial in cancer patients. Details of good manufacturing practice (GMP) synthesis and analysis of IL-2 liposomes (N= 6 lots) made without albumin carrier protein and placebo liposomes (three lots) are presented. After centrifugation, IL-2 was closely associated with the liposome pellet (99%). Mean diameter of liposomes was 1.1 microm. Patient acceptance, safety, toxicity, and immune effects of IL-2 liposomes were studied in individuals with primary immune deficiency (N = 15) and subsequently, a larger cohort of patients with hepatitis C. Experience in the immune deficient patients is the subject of this report. Placebo liposomes (12 weeks) and IL-2 liposomes (12 weeks) were provided using a nebulizer. Aerosol placebo liposomes and IL-2 liposomes were well tolerated. No changes in chest X-ray or pulmonary function were seen. Since biologic activity of aerosol IL-2 liposomes has been seen in viral disease (hepatitis C), additional studies of aerosol IL-2 liposomes in individuals with hepatitis C and HIV are planned.     

Ehrlich tumor inhibition using doxorubicin containing liposomes

Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm³) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.     

Preparation, characterization, and biodistribution study of technetium-99m-labeled leuprolide acetate-loaded liposomes in ehrlich ascites tumor-bearing mice

The purpose of this study was to prepare conventional and sterically stabilized liposomes containing leuprolide acetate in an attempt to prolong the biological half life of the drug, to reduce the uptake by reticuloendothelial system (RES), and to reduce the injection frequency of intravenously administered peptide drugs. The conventional and sterically stabilized liposomes containing leuprolide acetate were prepared by reverse phase evaporation method and characterized for entrapment efficiency and particle size. Radiolabeling of leuprolide acetate and its liposomes was performed by direct labeling with reduced technetium-99m. Its biodistribution and imaging characteristics were studied in ehrlich ascites tumor (EAT)-bearing mice after labeling with technetium-99m. The systemic pharmacokinetic studies were performed in rabbits. A high uptake by tumor was observed by sterically stabilized liposome containing leuprolide acetate compared with free drug and conventional liposomes. The liver/tumor uptake ratio of free drug, conventional (LL), and sterically stabilized liposomes (SLL5000 and SLL2000) was found to be 20, 7.99, 1.63, and 1.23, respectively, which showed the increased accumulation of sterically stabilized liposomes in tumor compared with the free drug and conventional liposomes at 24 hours postinjection. Liver uptake of sterically stabilized liposomes was still 7-fold less than the conventional liposomes. The marked accumulation of liposomes in the tumor-bearing mice was also documented by gamma scintigraphic studies. The findings demonstrate the distribution of these liposomes within solid tumor and prove that the sterically stabilized liposomes experience increased tumor uptake and prolonged circulation half life. Hence these findings will be relevant for the optimal design of long circulating liposomes for the peptide drugs and for targeting of liposomes toward tumor.     

Effect of surface ligand density on cytotoxicity and pharmacokinetic profile of docetaxel loaded liposomes

Various biotin-modified liposomes incorporated with docetaxel (DTX) were prepared to study the effect of surface biotin density on the pharmacokinetic profile of the liposome. Four types of liposomes such as PEG modified liposome (PDL), 0.5% (mol) biotin modified liposome (0.5BDL), 1% (mol) biotin modified liposome (1BDL) and 2% (mol) biotin modified liposome (2BDL) were prepared using thin film dispersion method. The prepared liposomes were characterized by measuring encapsulation efficiency (EE), particle size, Zeta-potential, physical stability and drug release profiles in vitro. MTT assay was performed to elevate the cytotoxicity of liposomes on MCF-7 cells. In vivo evaluation was further performed to investigate the effect of biotin surface density on the pharmacokinetic profiles. All the prepared liposomes exhibited high encapsulation efficiency, small particle size, narrow particle distribution and sustained release profiles in vitro. In MTT assay, 0.5BDL showed largest tumor cell toxicity, compared with DTX solution. All liposomes containing DTX showed prolonged blood circulation in vivo, and 0.5BDL showed the longest circulation time among the biotin modified liposome. Surface modification of liposome had a negative impact on the circulation of liposomes in the blood, which needs to be considered when designing the ligand mediated targeting delivery systems. A proper amount of biotin liposome with 0.5% molar ratio is expected to produce the best anti-tumor effect.     

Development and characteristics of temperature-sensitive liposomes for vinorelbine bitartrate

A novel liposome with temperature-sensitivity for vinorelbine bitartrate (VB) was designed to enhance VB targeted delivery and antitumor effect. Liposomes without drugs were prepared by thin film hydration, and then VB was entrapped into liposomes by pH gradient loading method. The mean particle size of the liposomes was about 100 nm, and the drug entrapment efficiency was more than 90%. Stability data indicated that the liposome was physically and chemically stable for at least 6 months at 4 °C. In vitro drug release study showed that drugs hardly released at 37 °C; while at 42 °C, drugs released quickly. For in vivo experiments, the lung tumor model was established by subcutaneous inoculation of cell suspension on mice, liposomes and free VB were injected i.v. in mice, followed by exposure the tumors to hyperthermia (HT) for 30 min after administration. The ratio of inhibition tumor of temperature-sensitive liposomes group was significantly higher than the normal injection group. Combining temperature-sensitive liposomes with HT enhanced the delivery of VB and, consequently, its antitumor effects. This liposome could potentially produce viable clinical strategies for improved targeting and delivery of VB for treatment of cancer.     

In Vitro andIn Vivo Studies of Different Liposomes Containing Topotecan

Liposome as a carrier of topotecan (TPT), a promising anticancer drug, has been reported in attempt to improve the stability and antitumor activity of TPT. However, the biodistribution pattern of TPT liposome in vivo and PEG-modified liposome containing TPT have not been studied systemically. In this paper, the in vitro stability and in vivo biodistribution behavior of several liposomes containing TPT with different lipid compositions and PEG-modification were studied. Compared with the 'fluid' liposome (S-Lip) composed of soybean phosphatidylcholine (SPC), the 'solid' liposome (H-Lip) composed of hydrogenated soybean phosphatidylcholine HSPC decreased the leaking efficiency of TPT from liposome and enhanced the stability of liposome in fetal bovine serum (FBS) or human blood plasma (HBP). The results of biodistribution studies in S180 tumor-bearing mice showed that liposomal encapsulation increased the concentrations of total TPT and the ratio of lactone form in plasma. Compared with free TPT, S-Lip and H-Lip resulted in 5- and 19-fold increase in the area under the curve (AUC(0-->infinity)), respectively. PEG-modified H-Lip (H-PEG) showed 3.7-fold increase in AUC(0-->infinity) compared with H-Lip, but there was no significant increase in t(1/2) and AUC(0-->infinity) for PEG-modified S-Lip (S-PEG) compared with S-Lip. Moreover, the liposomal encapsulation changed the biodistribution behavior, and H-Lip and H-PEG dramatically increased the accumulation of TPT in tumor, and the relative tumor uptake ratios were 3.4 and 4.3 compared with free drug, respectively. There was also a marked increase in the distribution of TPT in lung when the drug was encapsulated into H-Lip and H-PEG. Moreover, H-PEG decreased the accumulation of TPT in bone marrow compared with unmodified H-Lip. All these results indicated that the membrane fluidity of liposome has an important effect on in vitro stability and in vivo biodistribution pattern of liposomes containing TPT, and PEG-modified 'solid' liposome may be an efficient carrier of TPT.