ABSTRACT
Nanoparticles have better applicability in the detection, treatment of cancer and various difficult diseases, but mononuclear phagocytosis system can seriously shorten the time of nanoparticles in vivo circulation, reduce the drug efficacy. The protein crown formed on the surface of the nanoparticle after entering the body can change its surface properties, interfere with the recognition of phagocytes, and thus affect its circulation time in vivo. This article outlines the general composition and formation process of protein crowns. It also summarizes the influence of the physical and chemical properties of nanoparticles, such as particle size, surface charge, hydrophilicity and surface materials on the formation of protein crowns. The protein crown affects the circulation of nanoparticles in vivo, mainly because the adsorbed opsonic protein promotes cell phagocytosis. Therefore, we also introduce the method of using protein crowns to promote the long circulation of nanoparticles in vivo. By designing appropriate physical and chemical properties, surface modification, and directed design of protein crowns, the adsorption of proteins on the surface of nanoparticles can be reduced. Therefore, it can reduce the clearance of nanoparticles in the mononuclear phagocytic system (mainly the phagocytes of the liver and spleen), and achieve the goal of long circulation of nanoparticles in the body.
ABSTRACT
Objective: To prepare voriconazole long-circulation liposomes and evaluate the characteristics of pharmacokinetics in rats.Methods: Voriconazole long-circulation liposomes were prepared by a thin film dispersion extrusion method.The drug release of voriconazole from the long-circulation liposomes was investigated in phosphate buffer solution (PBS) and in rat plasma.The physicochemical properties of the long-circulation liposomes before and after the freeze-drying were studied, such as the particle diameter and the particle shape.The concentration of voriconazole in plasma was determined after tail-vein injection of the long-circulation liposomes in rats.Results: The mean particle size of voriconazole long-circulation liposomes was (192.1±49.3)nm with homogeneous small spherical morphology as seen under a transmission electron microscope.Voriconazole was released in a sustained manner in PBS while much faster in plasma from the long-circulation liposomes.The t1/2 and AUC0-t of the long-circulation liposomes was respectively 2.17 and 2.31 times higher than that of voriconazole injection.Conclusion: Long-circulation liposomes prolong the circulation time and increase the bioavailability of voriconazole.
ABSTRACT
Objective To establish a quick method to analyze vinorelbine ( NVB) in plasma of beagle dogs and study its pharmacokinetics of long-circulation and thermosensitive liposome loaded vinorelbine bitartrate.Methods The plasma was treated with liquid-liquid extraction after precipitation in methanol.The analysis was perfomed on a Venusil XBP C18 column(2.1 mm ×50 mm, 3 μm) at 35℃,the mobile phase consisted of methanol and water( containing 10 mmol/L ammonium acetate, 1%acetonitrile) 80∶20 and injection volume was 10μl.The type of mass spectrum was multireactive monitoring(MRM) in a positive mode.The monitor transitions were m/z 779.4-765.4 for vinorelbine and m/z 825.4-122 for vincristine.Results The concentration range from 10 to 2500 ng/ml had a good linearity ( r=0.0994).The precision, accuracy and extraction efficiency were acceptable.The plasma samples were stable for 10 days at -20℃ and 24 h at room temperature.Pharmacokinetic study in beagle dogs showed that the main parameters for injection and liposome were Cmax(833.51 ±150.42) and (1397.95 ±443.05)ng/ml, AUC(0-t) (577.16 ±223.57) and (1059.82 ±408.27) ng/ml· h, Cl(3014.64 ±1049.17)and 1633.10 ±551.77 ml/(h· kg), respectively.Conclusion A reliable HPLC-MS/MS method for vinorelbine analysis is established and can be applied to the pharmacokinetics study of liposome.The results show that liposome has a higher AUC, Cmax and longer Cl than injection.Meanwhile, liposome has a lower irritability.
ABSTRACT
Objective To prepare vinorelbine bitartrate long-circulation liposomes by pH gradient loading methods and make characterization. Methods The impact of hydration temperature and extrusion times on the blank liposome particle size was investigated;and the incubation temperature and in duration on size and encapsulation percentage of drug loading liposome particle was tested. The vinorelbine bitartrate long-circulation liposome was characterized for particle size,polydispersion index, Zeta potential,morphology,and was studied for long term stability. Results The particle size,Zeta potential,polydispersion in-dex of long-circulation liposomes were (96. 4±27. 2) nm,(0. 162±0. 042),(-26. 7±3. 5) mV,respectively. The liposomes were small,unilamellar and spherical with smooth surface under transmission electron microscopy. Long term stability studies showed that the liposomes were stable for up to 3 months after storage at 5 ℃ . Conclusion The preparation technology for the vinorel-bine bitartrate long-circulation liposome by pH gradient loading methods is feasible.
ABSTRACT
Objective To develop liposome loaded with paclitaxel for the treatment of lung cancer,novel phosphatidyl polyethyleneglycol monomethyl ether liposomes were prepared and studied.Methods A series of phosphatidyl polyethyleneglycol monomethyl ether liposomes were synthesized.Liposomes with or without drug were prepared by ultrasound.The entrapment efficiency and size of drug loaded liposomes were evaluated.The influence of liposomes to A549 lung cancer cell was investigated by MTT method.The cell uptake of liposome was observed by laser confocal scan microscope.Results The liposome loaded with paclitaxel had an entrapment efficiency of 83％ and size of 100～200 nm.The MTT results showed phosphatidyl polyethyleneglycol monomethyl ether liposomes loaded paclitaxel have inhibition effect to A549 cells with long circulation,while liposomes without paclitaxel have not inhibition effect.Conclusion Drug loaded polyethyleneglycol monomethyl ether liposomes have sustained delivery to paclitaxel.They have potential application in the therapy of cancer.