去甲斑蝥素/粉防己碱双载药脂质体的制备工艺及体外释放性质考察
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摘要
为优选去甲斑蝥素/粉防己碱双载药脂质体的处方及制备工艺,该实验以去甲斑蝥素介孔二氧化硅纳米粒(MSNNCTD)及粉防己碱(Tet)为药物,采用薄膜分散-超声法制备双载药脂质体,以粒径和包封率为综合指标,通过正交试验考察磷脂胆固醇用量、超声时间、超声功率对处方工艺的影响;采用透析法考察脂质体的体外释放特性。结果表明制备的去甲斑蝥素/粉防己碱双载药脂质体,最佳处方工艺为磷脂、胆固醇比2.5∶1,超声时间4 min,超声功率40%;NCTD与Tet的包封率分别为86.62%,79.19%;透射显微镜下可见脂质体外形良好,平均粒径(207.5±3.6)nm,Zeta电位(1.345±0.173)m V;NCTD与Tet的48 h累积释放率分别为85.14%,85.00%。实验结果证明薄膜分散-超声法制备双载药脂质体,包封率较高,粒径均匀,具有体外缓释特性。
In order to optimize the prescription and preparation process of norcantharidin/tetrandrine dual loaded liposomes,the dual drug loaded liposomes were prepared by film dispersion-ultrasonic method using norcantharidin-mesoporous silica nanoparticles( MSN-NCTD) and tetrandrine( Tet). With particle size and encapsulation efficiency as comprehensive indexes,the influences of phospholipid cholesterol amount,ultrasonic time and ultrasonic power on prescription process were investigated by orthogonal test; the in vitro release characteristics of liposomes were investigated by dialysis method. The results indicated that the best prescription process of prepared norcantharidin/tetrandrine dual loaded liposomes was as follows: phospholipid-cholesterol ratio 2. 5∶ 1,ultrasonic time 4 min,ultrasonic power 40%; the encapsulation efficiency was 86. 62% and 79. 19% respectively for NCTD and Tet; liposomes were wellshaped under the transmission microscope,with average particle size of( 207. 5 ± 3. 6) nm,Zeta potential of( 1. 345 ± 0. 173) m V;and the 48 h cumulative release rates of NCTD and Tet were 85. 14% and 85. 00% respectively. The experiment results proved that the dual drug loaded liposomes prepared by film dispersion-ultrasonic method had uniform particle size,high encapsulation efficiency and in vitro sustained release characteristics.
In order to optimize the prescription and preparation process of norcantharidin/tetrandrine dual loaded liposomes,the dual drug loaded liposomes were prepared by film dispersion-ultrasonic method using norcantharidin-mesoporous silica nanoparticles( MSN-NCTD) and tetrandrine( Tet). With particle size and encapsulation efficiency as comprehensive indexes,the influences of phospholipid cholesterol amount,ultrasonic time and ultrasonic power on prescription process were investigated by orthogonal test; the in vitro release characteristics of liposomes were investigated by dialysis method. The results indicated that the best prescription process of prepared norcantharidin/tetrandrine dual loaded liposomes was as follows: phospholipid-cholesterol ratio 2. 5∶ 1,ultrasonic time 4 min,ultrasonic power 40%; the encapsulation efficiency was 86. 62% and 79. 19% respectively for NCTD and Tet; liposomes were wellshaped under the transmission microscope,with average particle size of( 207. 5 ± 3. 6) nm,Zeta potential of( 1. 345 ± 0. 173) m V;and the 48 h cumulative release rates of NCTD and Tet were 85. 14% and 85. 00% respectively. The experiment results proved that the dual drug loaded liposomes prepared by film dispersion-ultrasonic method had uniform particle size,high encapsulation efficiency and in vitro sustained release characteristics.
引文
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[3]管敏,周奕,贝永燕,等.乳糖化-去甲斑蝥素抗肿瘤药效学及急性毒性试验研究[J].抗感染药学,2010,7(3):171.
[4]肖霞,陈英辉,洪震.粉防己碱逆转多药耐药的研究进展[J].上海中医药杂志,2011(4):78.
[5]Tang F,Li L,Chen D.Chem Inform abstract:mesoporous silica nanoparticles:synthesis,biocompatibility and drug delivery[J].Adv Mater,2012,24(12):1504.
[6]Troutier A L,Ladavière C.An overview of lipid membrane supported by colloidalparticles[J].Adv Colloid Interface Sci,2007,133(1):1.
[7]Haidar Z S,Hamdy R C,Tabrizian M.Protein release kinetics for coreesell hybrid nanoparticles based on the layer-by-layer assembly of alginate and chitosan on liposomes[J].Biomaterials,2008,29(9):1207.
[8]Troutier A L,Delair T,Pichot C,et al.Physicochemical and interfacial investigation of lipid/polymer particle assemblies[J].Langmuir,2005,21(4):1305.
[9]杨艳芳,谢向阳,杨阳,等.粒径与表面电荷影响脂质体体内药物靶向递送的研究进展[J].药学学报,2013(11):1644.
[10]Tsoi K M,Macparland S A,Ma X Z,et al.Mechanism of hardnanomterial clearance by the liver[J].Nat Mater,2016,15(11):1212.
[11]王国伟,贾伟东,张蓉蓉,等.Angiopep-2修饰核-壳介孔二氧化硅脂质囊纳米粒的制备及体外评价[J].中国药学杂志,2015,50(9):775.
[12]穆筱梅,梁世强.脂质体的制备方法及其研究进展[J].时珍国医国药,2008,19(7):1784.
[13]李春民,赵桂森,袁玉梅.RP-HPLC测定去甲斑蝥素含量及有关物质[J].中国药学杂志,2007,42(6):469.
[14]刘永刚,刘勇,何瑞杰,等.HPLC测定防己中防己诺林碱和粉防己碱的含量[J].中国实验方剂学杂志,2010,16(9):49.
[15]Shin S B,Chao H Y,Kim D D,et al.Preparation and evaluation of tacrolimus-loaded nanoparticles for lymphatic delivery[J].Eur J Pharm Biopharm,2010,74(2):164.
[16]Gullotti E,Park J,Yeo Y.Polydopamine-based surface modification for the development of peritumorally activatable nanoparticles[J].Pharmacol Res,2013,30(8):1956.
[17]陈春燕,徐萍,袁弘.口服聚乙二醇修饰固体脂质纳米粒的组织分布及抗肿瘤药效学研究[J].中国现代应用药学,2016,33(5):586.8
[18]闫颖,齐宪荣.以叶酸受体为靶向的阳离子脂质体的制备与性质考察[J].药学学报,2008,43(11):1134.
[19]Petros R A,De Simone J M.Strategies in the design of nanoparticles for therapeutic application[J].Nat Rev Drug Discov,2010,9(8):615.