ABSTRACT
Objective: To establish an in vitro model of brain blood barrier (BBB) using cultured mouse brain microvascular endothelial cells (BMVEC). Methods: Mouse BMVEC were seeded on micro pore membrane of gelatin coated cell culture insert and cultured to confluence. The establishment of BBB was preliminary judged by a 4 h water leaking test. The tight junctions between BMVEC were demonstrated by scanning and transmission electron microscope. The transendothelial electrical resistance(TEER) over BMVEC was measured. The permeability of Horseradish peroxidase (HRP) through the BBB was analyzed and the effect of RMP 7 on permeability of the BBB was investigated. Results: The 4 h water leaking test became positive when BMVEC were cultured to confluence. By scanning and transmission electron microscope, the tight junctions were demonstrated on confluent BMVEC. The TEER over BMVEC monolayer increased 3.2 and 7.68 times and the permeability rates for HRP were 13.4% and 6.7% respectively, as compared with sub confluent BMVEC and human umbilical vein endothelial cell monolayer(HUVEC). The HRP permeability rate in the model of BBB increased 2.7 times after treatment with RMP 7. Conclusion: The established in vitro model of BBB has basic characteristics of BBB in vivo , and is suitable for central nervous system (CNS) drug research over BBB.
ABSTRACT
<p><b>OBJECTIVE</b>To study the effects of chemoembolization with adriamycin alginate-chitosan microcapsules in the treatment of VX2 carcinoma in the extremity of the rabbit.</p><p><b>METHODS</b>Twenty-four New Zealand white rabbits transplanted with VX2 carcinoma cells into the muscle tissue of the lower right thigh were divided into four groups namely groups A, B, C and D, and received regional infusion from femoral artery. Each group consisted of six rabbits: a group given natural saline (Group A), a group given adriamycin (Group B), a group given blank alginate-chitosan microcapsules (Group C) and a group given adriamycin alginate-chitosan microcapsules (Group D). Three days after treatment, all groups were examined by histology and immunohistochemical detection (TdT-mediated dUTP nick end labeling technique, TUNEL; proliferating cell nuclear antigen, PCNA).</p><p><b>RESULTS</b>The blood vessels of the tumor were almost embolized by the microcapsules. Extensive necrosis, high level of positive cells in TUNEL (60.85% +/- 5.21%) and low level in PCNA detection with in the tumors were observed in Group D.</p><p><b>CONCLUSION</b>Adriamycin alginate-chitosan microcapsules can potentially play roles in two respects, 1 to serve as embolizing agents, and 2 to serve as drug delivery vehicles for local release. Chemoembolization with microparticals is an effective treatment of malignant osseous and soft tissue sarcomas in an experimental model.</p>
Subject(s)
Animals , Rabbits , Alginates , Capsules , Chemoembolization, Therapeutic , Chitin , Chitosan , Disease Models, Animal , Doxorubicin , Glucuronic Acid , Hexuronic Acids , In Situ Nick-End Labeling , Neoplasms, Experimental , Drug Therapy , Pathology , Proliferating Cell Nuclear AntigenABSTRACT
Objective: To compare the pharmacokinetic c haracteristics of amphoterici n B liposomes injection (LAmB) with market amphotericin B injection (MAmB) in ra bbits by intravenous administration. Methods: LAmB and MAmB wer e intravenously ad ministrated to rabbits at a single dosage of 1 mg*kg －1. The AmB concent rations i n plasma samples were determined by HPLC, and the pharmacokinetic parameters wer e calculated by means of 3P97, and ANOVA were done by means of the Excel softwar e. Results: The concentration- time data of LAmB and MAmB after intravenous administration were best fitted acc ording to three compartment-model with a weight of 1/C and 1 respectively . After a singl e intravenous administra tion, C max of LAmB and MAmB were 8.4±2.1 and 2.4±0.6 mg*L －1, AUC were 22.5±6.8 and 9.0±1.9 mg*h*L －1, CL were 0.050±0 .024 and 0.114 ±0.022 L*h －1, V c were 0.13±0.04 and 0.46±0.18 L , respectively. Comparing with MAmB, all rabbits showed high plasma levels, large area under the curve values and low cl earance, small apparent volume of distribution of LAmB. Conclusion: There were several striking differences between the pharmacokinetics properties of LAmB and MAmB in jection in rabbits. All changes of the pharmacokinetics properties will be advan tageous to reduce toxicity and improve therapeutic effect.
ABSTRACT
Objective: To study the possibility of liposomes to ta rget hepatocytes af ter being linked with asialofetuin(AF). Methods: The biodistribu tions in differen t cells in liver as well as in blood, in various organs such as heart, spleen, l ung and kidney of mice, of traditional sterically stabilized liposomes(SSL) , AF-linked normal liposomes(AF-NL) and AF-linked sterically stabilized lipos ome s(AF-SSL) were studied by radioisotopic labeling. Results: The half-live s of SSL, AF-NL and AF-SSL were 14.44, 4.73 and 11.49 h， respectively. The di strib ution of liposomes in liver was AF-NL>AF-SSL>SSL. There was significant differenc e among these three formulations. In hepatocytes and non-hepatocytes, the conce ntr ations of the liposomes were both in line with the sequence AF-NL>AF-SSL>SSL( P <0.05). However, the ra tios of the concentrations in hepatocytes to that of non-hepatocytes were AF-N L≈AF -SSLSSL( P <0.05). Conclusion: After being labeled with asi alofetuin, liposomes can target hepatocytes very we ll， whether in long-circulation or not.