˫�����۾����񾭶���֬������Ʊ����侭���Ĥ��ҩ���ڴ�������ҩ��ѧ�о�

??OBJECTIVE To investigate the brain pharmacokinetics of co-modified liposomes of ??-cobrotoxin in rats after intranasal administration. METHODS DSPE-PEG₂₀₀₀-Pep1 and DSPE-PEG₂₀₀₀-Pep2 were synthesized by Michael addition reaction. And their structures were verified by proton nuclear magnetic resonance spectroscopy (¹H-NMR) and infrared spectroscopy (FTIR). Pep2(Pep1)-??CT-LP was prepared by the method of thin-film hydration and post-inserting, then its morphology, particle size, and Zeta potential were investigated. The encapsulation efficiency of liposomes was determined by ultrafiltration centrifugal method. The concentrations of ??CT-LP, Pep1-??CT-LP, Pep2-??CT-LP, and Pep2(Pep1)-??CT-LP in periaqueductal gray (PAG) after intranasal administration were measured by microdialysis and the pharmacokinetical parameters were analyzed by PKSolver software. RESULTS The structures of DSPE-PEG₂₀₀₀-Pep1 and DSPE-PEG₂₀₀₀-Pep2 were proved by ¹H-NMR and FTIR. The prepared Pep2(Pep1)-??CT-LP was nearly spherical with uniform size, the mean particle size was (115.8??1.86) nm, and the Zeta potential was (-13.77??0.75) mV. Besides, the encapsulation efficiency was (32.75??1.12)%. The RESULTS of in vivo test demonstrated that the ??CT concentrations in PAG after intranasal administration of Pep2(Pep1)-??CT-LP were significantly increased compared with the groups of ??CT-LP, Pep1-??CT-LP and Pep2-??CT-LP(P??0.05). The ??_max, t_max, and AUC_0???? were (244.72??3.15) ng??mL^-1, (88.01??4.19) min, (89 199.02??1 922.99) ng??min??mL^-1, respectively. CONCLUSION Pep2(Pep1)-??CT-LP can significantly increase the concentrations of ??CT in periaqueductal gray, which provides a promising method for development of polypeptide agents for brain-targeting.     

�����ع���֬�����������Ʊ������������о�

??OBJECTIVE To prepare capsaicin-solid lipid nanoparticles (CAP-SLNs) and study their physical and chemical properties. Then, the CAP-SLNs were modified with chitosan (CTS) and the pharmacokinetics across colon of rats was studied in vivo. METHODS CAP-SLNs were prepared by emulsion-solvent evaporation method. The mean size, encapsulation efficiency and drug loading of the nanoparticles were investigated. RESULTS The average diameter of CAP-SLNs was (118.89??25.0) nm, the encapsulation efficiency was (38.56??2.6)%, and the drug-loading was (6.17??0.21)%. After colon-specific delivery in rats, the AUC_{0-360 min}(243.63??61.46) mg??min??L^-1 and ??_max(1.23??0.18) mg??L^-1 of CTS-CAP-SLNs were 1.81-fold and 1.95-fold higher than CAP. CONCLUSION It is simple and feasible to prepare CAP-SLNs by emulsion-solvent evaporation method. The pharmacokinetic parameters in rats are improved remarkably compared with CAP.     

�嶡��-ˮ���ܼ���ϵ���ɷ��Ʊ�������ɼ��֬����

??OBJECTIVE To prepare docetaxel liposomes by freeze-drying of tert-butyl alcohol (TBA)/water cosolvent system and evaluate the in vitro and in vivo properties. METHODS The formulation was optimized by single factor screening experiments. The effects of TBA/water ratio, lipid/drug ratio, sucrose/lipid ratio and mixing temperature on encapsulation efficiency were investigated. The in vitro release profiles were also investigated with docetaxel injection(Duopafei^?k) as control. RESULTS The formulated liposomes had a mean size of 263 nm with entrapment efficiency of (88.45??1.63)% at TBA/water ratio 50??50, lipid/ drug ratio 10??1, sucrose/lipid ratio 5??1 and mixing temperature 60 ??. In vitro drug release from liposomes lasted for 48 h. CONCLUSION Freeze-drying of TBA/water cosolvent system method may be feasible to prepare docetaxel liposomes.     

��ɼ���������֬������Ʊ�������ҩЧѧ�Ͱ�ȫ������

??OBJECTIVE To synthesize a prodrug of paclitaxel which is modified by palmitic acid at the 2??-hydroxyl position and prepare paclitaxel palmitate liposomes(PTX-PA-L), and then compare the pharmacodynamics and safety of PTX-PA-L in S180 tumor-bearing rats with paclitaxel injection. METHODS The derivative of paclitaxel was synthesized using 4-dimethylaminopyridine(DMAP) as acid binding agent and 1-(3-dimethylaminopropyl)-3-ethylenediamine(EDC) as dehydrating agent. PTX-PA was characterized by mass spectrometry and nuclear magnetic resonance spectroscopy(600 MHz ¹H-NMR). PTX-PA-L were prepared using film dispersion-ultrasonic method. The particlesize and Zeta potential were measured using Malvern Zeta-sizer Nano S and the morphologywas characterized by TEM. The S180 sarcoma model in ICR mice was established to study the antitumor efficiency of PTX-PA-L in vivo. The hematological toxicity and body weight change of the mice were evaluated to study the safety of PTX-PA-L. RESULTS The prodrug PTX-PA was synthesized successfully. The liposomes had good morphological characteristics and light blue opalescence and the particle size was(104.82??1.23) nm. The pharmacodynamic study showed that compared with paclitaxel injection, PTX-PA-L had better antitumor efficacy on S180 tumor-bearing mice and the blood index indicated less decrease of white blood cells and neutrophils. CONCLUSION PTX-PA-L can improve the antitumor efficacy significantly and reduce the toxicity of paclitaxel injection.     

ת���������ε�ȥ��������������֬������Ʊ�������Ч������

??OBJECTIVE To prepare the transferrin modified harmine magnetoliposomes and investigate its in vitro properties and antitumor effect. METHODS Transferrin modified harmine magnetoliposomes was prepared by reverse phase evaporation method. The size, Zeta potential, entrapment efficiency, drug loading efficiency, release rate and plasma stability of liposomes were investigated. Furthermore, cytotoxicity to liver cancer and glioma were investigated too. RESULTS The transferrin modified harmine magnetoliposomes were successfully prepared. The average size of liposomes was (184.7??8.08)nm.The average Zeta potential was (-12.4??0.896) mV and average entrapment efficiency was (84.67??6.26)%. Drug loading efficiency was (9.14??4.54)%. Transferrin modified harmine magnetoliposomes released more slowly and were more stable in rat plasma than harmine solution. The results of cytotoxicity test showed that the cell inhibitory effect of transferrin modified harmine magnetoliposomes was enhanced compared with other groups, and the cell inhibitory effect of this preparation was more obvious underwhen cells were put under magnetic field compared with those under the non-magnetic field(P<0.05). CONCLUSION This method can be successfully used to prepared transferrin modified harmine magnetoliposomes, and liposomes can inhibit the cell visbility of liver cancer and human glioma cells significantly.     

�๦�ܰ����Ա������֬������Ʊ�������Խ�����ϸ��������ЧӦ

??OBJECTIVE To develop a kind of multifunctional targeting epirubicin liposomes for the treatment of brain tumor, to characterize their physicochemical properties, and to observe their targeting effects on the brain microvascular endothelial cells(BMVECs)and on the brain glioma cells.METHODS The 2-amino-2-deoxy-??-D-glucopyranose(NH₂-Glu)was used as a targeting molecule and conjugated with a cholesterol-polyethylene glycol derivative (Chol-PEG₂₀₀₀-NHS) for obtaining the targeting functional material aimed at targeting to glucose transporter-1(Glut-1)on the BMVECs of blood-brain barrier and further targeting to the glioma cells. To prepare the multifunctional targeting epirubicin liposomes, the targeting functional material was modified onto the surface of liposomes, and epirubicin was loaded into the core of liposomes as the anticancer drug. The encapsulation efficiency, particle size, polydispersity indexes and Zeta potential of the liposomes were measured, their cellular uptakes were performed on the BMVECs and the glioma cells. The inhibitory effect was performed on the glioma cells. RESULTS The analysis by MALDI-TOF-MS demonstrated that the targeting functional material, Chol-PEG₂₀₀₀-Glu, was successfully synthesized. The multifunctional targeting epirubicin liposomes were prepared, and had an average particle size of approximately 125 nm, and were negatively charged. The encapsulation efficiency of epirubicin in the liposomes was about 93%. Results from flow cytometry indicated that the multifunctional targeting epirubicin liposomes had the highest cellular uptakes by BMVECs and by two kinds of brain glioma cells as compared with no-targeting epirubicin liposomes. The cytotoxic study showed that the multifunctional targeting epirubicin liposomes had the strongest inhibitory effect to brain glioma cells as compared with free epirubicin or no-targeting epirubicin liposomes. CONCLUSION A new targeting material (Chol-PEG₂₀₀₀-Glu) and the multifunctional targeting epirubicin liposomes are developed, and the multifunctional targeting epirubicin liposomes exhibit the potential fortransporting across the blood-brain barrier (BBB), and selectively inhibiting the brain glioma cells.
     

N,N-���׻�-[N��,N��-˫(Ӳ֬����-1-�һ�)]1,3-�������ĺϳɡ����ʼ���Ϊ�װ����������Ӧ��

??OBJECTIVE To synthesize a novel cationic lipid,N,N-dimethyl-[N??,N??-di-(stearoyl-1-ethyl)] 1,3-diaminopropane (DMSP),and evaluate its feasibility as methotrexate(MTX) carrier. METHODS DMSP and phosphatidylcholine were employed to prepare liposomes by reverse phase evaporation method,and then MTX was entrapped by physical mixing. The entrapment efficiency was determined by ultracentrifugation,and its release ratio was evaluated by dialysis. The morphology of liposomes was observed under transmission electron microscope. The average diameter and Zeta potential were determined by laser particle size analyzer. MTT test was used to evaluate the cytotoxicity of liposomes as drug carrier and the inhibition of cancer cells growth. RESULTS The obtained liposomes showed regular shape and uniform size,with a mean Zeta potential of +(36.26??4.77)mV and average diameter of 120 nm. The liposomes had low hemolytic activity and cytotoxicity. With the help of DMSP the cationic liposomes achieved a very high entrapment efficiency for the hydrophilic drug MTX (91.50??1.02)%. The inhibition of the MTX liposomes on cancer cells growth was much higher than that of MTX solution. CONCLUSION DMSP is a novel cationic lipid with low cytotoxicity and high entrapment efficiency,which has a great application potential in drug delivery system.     

�ʲݴ���������鵼֬����������ȶ�������

??OBJECTIVE To evaluate the physical stability of glycyrrhetinic acid derivatives-mediated coumarin 6(Cou6) liposomes and confirm the applicability of different stability tests on liposomes. METHODS Film dispersion-ultrasonic method was used to prepare Cou6 liposomes, PEG-modified liposomes and glycyrrhetinic acid-mediated liposomes. The stability constants, membrane stability, serum stability and leakages of the six kinds of liposomes were studied. RESULTS The physical stability of the liposomes without modification was poor. As for the glycyrrhetinic acid-mediated liposomes, the stability constants at 15 min were 5.37-7.32 and the concentrations of Triton X-100 were 0.207??-0.380?? when half liposome membranes were destroyed. The serum stability in 24 h and leakages in 7 or 14 d showed good stability with little change. CONCLUSION The physical stability is one of the key pharmaceutical properties of liposomes. The stability constant, serum stability and leakage tests and the method of membrane stability we have established can be used to study the stability of liposomes.     

â���մ�������Ʊ����侭Ƥ��ҩ���Ե��о�

??OBJECTIVE To prepare mangiferin transfersomes and investigate its transdermal delivery characteristics. METHODS Mangiferin transfersomes were prepared by the method of film-dispersion, the in vitro percutaneous penetration study was conducted in the modified Franz diffusion cell, the distribution of transfersomes in skin was investigated by fluorescent tracer method, and the rat back airbag inflammation model was used to preliminarily evaluate the anti-inflammatory effect of mangiferin transfersomes with prostaglandin E2 (PGE2) content as the indicator. RESULTS The average particle size of mangiferin transfersomes was (84.50??5.26)nm, the polydispersity index (PDI) was (0.21??0.012), the Zeta potential was(-10.83??0.66)mV, the encapsulation efficiency (EE) was (64.07??2.10)%,and the deformability was(20.00??0.30)%; the cumulative permeation quantities in 24 h and intradermal retention of mangiferin transfersomes were (313.67??22.62) and (60.34??8.10) ??g??cm^-2, respectively. Fluorescent tracer method showed that the fluorescence intensity of FITC transfersomes in the inside of skin was stronger than that of FITC solution at 8 h. Anti-inflammatory test showed that the PGE2 contents in the middle and high dose mangiferin transfersomes groups decreased significantly. The anti-inflammatory effect of the high dose mangiferin transfersomes was even close to that of compound dexamethasone cream. CONCLUSION Transfersomes can promote the percutaneous penetration of mangiferin, increase its intradermal retention, and enhance the anti-inflammatory effect of mangiferin significantly.