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排序方式: 共有1930条查询结果,搜索用时 15 毫秒
1.
Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals. 相似文献
2.
Perry Guaglianone Kenneth Chan Eduardo DelaFlor-Weiss Rosemarie Hanisch Susan Jeffers Desh Sharma Franco Muggia 《Investigational new drugs》1994,12(2):103-110
Summary We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial doseescalation steps from 10 to 60 mg/m2. At 80 mg/m2, two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m2. Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m2 in previously treated and 120 mg/m2 of DaunoXome in previously untreated patients with solid tumors.EDW is supported in part by ACS award 92-14-1 相似文献
3.
三氧化二砷脂质体的制备及其对鼠脑胶质瘤的影响 总被引:1,自引:0,他引:1
目的研究三氧化二砷(As2o3)脂质体注射液对大鼠体内C6胶质瘤细胞凋亡的影响。方法采用超声薄膜分散法制备As籼脂质体,将126只成瘤大鼠分为As2O3脂质体组、As2O3组、生理盐水组。原子荧光法检测注射As2O3脂质体和As2O3后大鼠脑组织中As2O3浓度。从电镜、TUNNEL和大鼠生存时间等方面研究As2O3脂质体对C6胶质瘤的影响。结果As203,脂质体提高了As2O3的血-脑屏障通过。电镜和TUNEL检测显示:As203脂质体组细胞凋亡率给药后3d为(13.53±1.68)%,7d为(20.03±0.79)%,多于As2O3组和盐水组。动物生存时间亦优于其他两组。结论超声薄膜分散法是制备As2O3脂质体的较好方法。As203脂质体可较As203更明显地诱导鼠脑胶质瘤细胞凋亡,延长载瘤鼠的生存期。 相似文献
4.
Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells. 总被引:2,自引:1,他引:1
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W M Bogers R K Stad D J Janssen N van Rooijen L A van Es M R Daha 《Clinical and experimental immunology》1991,86(2):328-333
In the present study we have investigated the clearance kinetics and tissue distribution of monomeric (m) IgG and soluble aggregates of IgG (AIgG) and immune complexes (IC) in normal and Kupffer cell (KC) depleted rats. In normal rats, clearance of mIgG occurred in a biphasic manner with a first half-life (T1/2) (T1) of 36.3 +/- 6.3 min and a second T1/2 (T2) of 168.4 +/- 4.7 min. AIgG composed of 20-27 IgG molecules per aggregate were cleared significantly faster than mIgG with a T1 of 2.5 +/- 0.1 min and a T2 of 32.5 +/- 5.6 min. KC depletion did not have a significant effect on the clearance rate of mIgG (T1: 33.4 +/- 8.9 min; T2; 159.5 +/- 12.5 min), while clearance of AIgG was delayed significantly with T1 4.8 +/- 0.7 min and T2 41.2 +/- 3.2 min. Eight minutes after injection, 77% of AIgG was found in the liver in normal rats while 62% was found in the liver of KC-depleted rats. Double immunofluorescence studies indicated that AIgG in the liver was associated with KC and endothelial cells (EC) in normal rats. In KC-depleted rats, AIgG was strongly associated with EC. A similar staining pattern was observed when IgG-immune IC were administered. The clearance of AIgG in KC-depleted rats was inhibited fully by pre-administration of high concentrations of IgG but not by pretreatment with IgA. asialofetuin (ASFe) or ovalbumin (OVA). Aggregated F(ab')2IgG was cleared with a comparable rate to mIgG from the circulation, again suggesting Fc gamma receptor-mediated elimination of AIgG by EC. There was a reduced degradation of AIgG in rats depleted of KC as compared with normal rats. These data suggest binding and degradation of AIgG by EC in vivo. 相似文献
5.
V. UMBRAIN J. D'HAESE M. ALAFANDY E. DE ROOVER A. SCHOUTENS B. VAN GANSBEKE A. ALBERT G. GOFFINET F. CAMU F. J. LEGROS 《Acta anaesthesiologica Scandinavica》1997,41(1):25-34
Background: Liposomes containing local anaesthetics have been administered intrathecally and in the epidural space. Poor attention has been given to the pharmacokinetics of liposomes as drug carriers. Therefore, we observed the biodistribution of liposomes after intrathecal injection in rats by scintigraphic imaging during 24 h.
Methods: We administered99 Tc-labeled multilamellar (MLV) and small unilamellar vesicles (SUV) of defined size and volume dispersities into the cerebrospinal fluid at the lumbar level. Those vesicles were free of contamination by radiolabeled colloids as visualized by light and electron microscopy and of neurotoxic products from phosphatidylcholine hydrolysis and peroxidation, both during the preparation process and after 24 h incubation in cerebrospinal fluid at 37°C in vitro.
Results: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 μm diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (±8 μm) could accumulate in the head with a slow elimination rate.
Conclusion: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use. 相似文献
Methods: We administered
Results: SUV immediately diffused from the lumbar site of injection to the head and were cleared between 1 and 24 h after injection. MLV were cleared more slowly from the spinal space and appeared in the head region 1 h after injection where they accumulated up to 24 h. These differences were explained in terms of vesicle sizes and volumes. SUV with 0.05 μm diameters were rapidly absorbed into the blood through the arachnoid granulations. In contrast, particles larger than the upper size limit of the arachnoid granulations permeability (±8 μm) could accumulate in the head with a slow elimination rate.
Conclusion: This difference in clearance from the intrathecal space outlines the importance of defining the size of the liposomes, the distribution of a tracer or a drug inside the liposomal preparation, the chemical stability and the absence of toxic degradation products of liposome formulations before clinical use. 相似文献
6.
Temperature sensitive liposomes (TSL) containing adriamycin (ADM) and cytarabine (Ara-C) were prepared. ADM and Ara-C were
selected as model compounds of amphiphilic and hydrophilic drug, respectively. Encapsulation efficiency of ADM entrapped into
TSL was about twice greater than that of Ara-C. It might be due to different polarity of the drugs. Lipid compositions of
TSL had no effect on the encapsulation efficiency of drugs. Thermal behavior of TSL using a differential scanning calorimetry
(DSC) was also investigated. Phase transition temperature (Tc) of TSL was dependent on the lipid compositions of TSL.ADM broadened thermogram of TSL but Ara-C did not. However, Tc of TSL was not changed by any drug. Release rate of drugs was highly dependent on temperature. The release profile of ADM
was similar to that of Ara-C. The maximum release rate of drugs from TSL was occurred at the near Tc and observed at 39–41°C for DPPC (Dipalmitoylphosphatidylcholine) only, 52–54°C for DSPC (Distearoylphosphatidylcholine)
only, 41–43°C for DPPC and DSPC (3∶1), and 43–45°C for DPPC and DSPC (1∶1), respectively. Effect of human serum albumin (HSA)
on the release rate of ADM was investigated. HSA had no significant effect on the release of ADM below Tc. However, ADM release from TSL was increased at the near and above Tc. The HSA-induced leakage of drug may result from the interaction of liposomal constituents with HSA structure at the near
Tc. From the fact that the release profiles of ADM from freshly prepared TSL and stored TSL for 1 week at 4°C was not changed,
the TSL was considered to be stable for at least 1 week at 4°C. Based on these findings, TSL may be useful to deliver drugs
to preheated target sites due to its thermal behaviors. 相似文献
7.
8.
Liposomes as drug carriers in cancer chemotherapy have attracted considerable interest. To enhance the therapeutic effect of Adriamycin entrapped in liposomes (Lip-ADM) on human solid tumors, we investigated the therapeutic effects of Lip-ADM in combination with recombinant human tumor necrosis factor-alpha (rTNF-alpha), which is known to have specific effects on tumor vasculature. rTNF-alpha or saline solution was injected intravenously into nude mice bearing a human colon cancer strain, HC-1, at 1 hour before intravenous administration of Lip-ADM. The significant therapeutic effect of Lip-ADM in combination with rTNF-alpha was demonstrated by the evaluation with tumor growth curve and the actual tumor weights, in comparison with groups of mice treated with saline solution, rTNF-alpha alone, or with a Lip-ADM after saline. Levels of Adriamycin in tumor tissue in the Lip-ADM in combination with rTNF-alpha-treated group were higher than those in Lip-ADM with saline solution-treated group. 相似文献
9.
WANGXiang-tao HOUXin-pu 《中国药学》2003,12(3):171-172
Becauseofvariousthrombolyticagentsnowavailableassociatedwithlowthrombolyticspecificity ,largedoserequiredforclinicaltreatment,andperplexingsideeffectofhemorrhage ,westudiedthethrombus targetedliposomeswhichhavespecificaffinitytoactivatedplatelets .WithtetrapeptideRGDSasthehomingdevice ,theobtainedliposomescanspecifi callyrecognizethereceptorGPIIb IIIaoftheactivatedplateletsinthrombus ,bywhichthrombustargetabilityisachieved .Thefollowingpartsareincludedinthestudy .Eggphosphatidylcholine (E… 相似文献
10.
Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells. 总被引:3,自引:1,他引:2
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W M Bogers R K Stad D J Janssen F A Prins N van Rooijen L A van Es M R Daha 《Clinical and experimental immunology》1991,85(1):128-136
We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes. 相似文献