酒石酸长春瑞滨壳聚糖纳米粒的制备及质量评价
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摘要
目的制备酒石酸长春瑞滨壳聚糖纳米粒(Vin-loaded CNs)并评价其质量。方法采用离子胶凝化法制备Vin-loaded CNs,以壳聚糖质量浓度(X_1)、三聚磷酸钠的质量浓度(X_2)和搅拌时间(X_3)作为考察因素,以平均粒径(Y_1)和包封率(Y_2)作为评价指标,使用Box-Behnken实验设计进行处方优化,采用激光粒度仪测定粒径分布、多聚分散系数(PdI)和ζ电位,透射电镜观察其微观形态;比较Vin-loaded CNs在pH值为7.4的磷酸盐(PBS)缓冲液和大鼠血浆中的释药速率。结果优化得到Vin-loaded CNs的最优处方为:壳聚糖质量浓度为0.50 mg·mL~(-1),三聚磷酸钠质量浓度为0.49 mg·mL~(-1),搅拌时间为60 min,Vin-loaded CNs的包封率为77.8%±1.6%;平均粒径为391.6±6.3 nm,ζ电位为23.2±2.6 mV;用透射电镜可观察到Vin-loaded CNs呈近似球形分布,粒径较均匀;在pH值为7.4 PBS缓冲液和大鼠血浆中释药平缓。结论将酒石酸长春瑞滨制成壳聚糖纳米粒稳定性好,体外释药缓慢,有望提高药物疗效。
Objective To prepare vinorelbine bitartrate-loaded chitosan nanoparticles(Vin-loaded CNs) and evaluate its physical and chemical properties.Methods The Vin-loaded CNs were prepared by iron gelation method.The chitosan mass concentration(X_1),sodium tripolyphosphate concentration(X_2) and stirring time(X_3) were used as independent variables.The average particle size(Y_1) and encapsulation efficiency(Y_2) were used as dependent variables.The formulation variables were optimized by Box-Behnken experimental design.The particle size distribution,PdI,and Zeta potential were measured with a laser particle size analyzer.The microscopic morphology was observed by transmission electron microscopy.The in vitro release rates of Vin-loaded CNs were compared.Results The formulation of Vin-loaded CNs was optimized as follows:chitosan concentration 0.50 mg·mL~(-1),sodium tripolyphosphate concentration 0.49 mg·mL~(-1),and stirring time 60 min.The average particle size was 391.6±6.3 nm.The encapsulation efficiency and Zeta potential of Vin-loaded CNs were 77.8 %±1.6 % and 23.2±2.6 mV,respectively.Transmission electron microscopy showed that the Vin-loaded CNs were nearly spherical and the particle size was uniform.The Vin-loaded CNs released slowly in pH 7.4 release media and rat plasma.Conclusion In this study,vinorelbine tartrate was prepared into chitosan nanoparticles with good stability,slow drug release in vitro,and is expected to improve the drug treatment efficiency.
Objective To prepare vinorelbine bitartrate-loaded chitosan nanoparticles(Vin-loaded CNs) and evaluate its physical and chemical properties.Methods The Vin-loaded CNs were prepared by iron gelation method.The chitosan mass concentration(X_1),sodium tripolyphosphate concentration(X_2) and stirring time(X_3) were used as independent variables.The average particle size(Y_1) and encapsulation efficiency(Y_2) were used as dependent variables.The formulation variables were optimized by Box-Behnken experimental design.The particle size distribution,PdI,and Zeta potential were measured with a laser particle size analyzer.The microscopic morphology was observed by transmission electron microscopy.The in vitro release rates of Vin-loaded CNs were compared.Results The formulation of Vin-loaded CNs was optimized as follows:chitosan concentration 0.50 mg·mL~(-1),sodium tripolyphosphate concentration 0.49 mg·mL~(-1),and stirring time 60 min.The average particle size was 391.6±6.3 nm.The encapsulation efficiency and Zeta potential of Vin-loaded CNs were 77.8 %±1.6 % and 23.2±2.6 mV,respectively.Transmission electron microscopy showed that the Vin-loaded CNs were nearly spherical and the particle size was uniform.The Vin-loaded CNs released slowly in pH 7.4 release media and rat plasma.Conclusion In this study,vinorelbine tartrate was prepared into chitosan nanoparticles with good stability,slow drug release in vitro,and is expected to improve the drug treatment efficiency.
引文
[1] 李楠.重酒石酸长春瑞滨靶向制剂抗肿瘤活性研究[D].哈尔滨:东北林业大学,2012:5.
[2] 王彩霞,魏娜,毕宇鑫,等.酒石酸长春瑞滨脂质体的体内抗肿瘤作用研究[J].中国药学杂志,2013,48(20):1733-1736.
[3] 张兰风,孟凡迅,张金业,等.长春瑞滨渗漏后皮下注射解毒剂的实验研究[J].中国实用护理杂志,2005,21(7):325-327.
[4] 牛砚涛,董文娜,唐星,等.酒石酸长春瑞滨亚微乳注射液的稳定性[J].沈阳药科大学学报,2013,30(3):165-170.
[5] 王莉芳,王彩霞,魏娜,等.酒石酸长春瑞滨脂质体注射液的安全性及抗肿瘤作用研究[J].中国药理学通报,2012,28(11):1627-1628.
[6] 农春梅,雷小光.盐酸度洛西汀壳聚糖微球的制备与表征[J].西北药学杂志,2010,25(4):283-286.
[7] 张洪,沈瑶,闫士君,等.青蒿琥酯-壳聚糖纳米粒的制备及质量评价[J].中国医院药学杂志,2013,33(5):349-355.
[8] 马茜,范娟.壳聚糖纳米粒载体的应用研究进展[J].西北药学杂志,2015,30(2):213-215.
[9] Javia A,Thakkar H.Intranasal delivery of tapentadol hydrochloride-loaded chitosan nanoparticles:formulation,characterisation and its in vivo evaluation[J].J Microencaps,2017,34(7):644-658.
[10] Fazil M,Md S,Haque S,et al.Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting[J].Eur J Pharm Sci,2012,47(1):6-15.
[11] 颜承云,谷继伟,王曦,等.N-琥珀酰壳聚糖纳米粒肿瘤靶向性及抗肿瘤活性评价[J].中国现代应用药学,2010,27(10):868-873.
[12] Hu Y,Jiang X Q,Ding Y,et al.Synthesis and charaeterization of chitosan poly (aeryli acid) nanoparticles[J].Biomaterials,2002,23(15):3193-3201.
[13] Shikata F,Tokumitsu H,Iehikawa H,et al.In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capyure therapy of caneer[J].Eur J Pharm Biopharm,2002,53(1):57-63.
[14] 谢向阳,陈晨,林雯.重酒石酸长春瑞滨长循环脂质体的制备与表征[J].医药导报,2015,34(3):379-384.
[15] 郝吉福,房信胜,王建筑,等.应用Box-Behnken实验设计优化水飞蓟素固体脂质纳米粒处方研究[J].中草药,2011,42(11):2221-2225.
[16] 王子臣,赵文明.星点设计-效应面法优化制备吉非替尼壳聚糖鱼精蛋白纳米粒[J].中国新药杂志,2016,25(7):807-812.
[17] Lee D W,Marasini N,Poudel B K.Application of Box-Behnken design in the preparation and optimization of fenofibrate-loaded self-microemulsifying drug delivery system (SMEDDS)[J].J Microencaps,2014,31(1):31-40.
[18] Xie F,Ding R L,He W F.In vivo antitumor effect of endostatin-loaded chitosan nanoparticles combined with paclitaxel on Lewis lung carcinoma[J].Drug Deliv,2017,24(1):1410-1418.
[19] Sahin A,Yoyen-Ermis D,Caban-Toktas S.Evaluation of brain-targeted chitosan nanoparticles through blood-brain barrier cerebral microvessel endothelial cells[J].J Microencaps,2017,34(7):659-666.
[20] 张玮,张学农.壳聚糖纳米粒制备技术研究进展[J].抗感染药学,2008,5(2):65-69.
[21] 谢黎崖,柯金珍,陈月,等.壳聚糖纳米粒制备研究进展及在靶向给药系统中的应用[J].中国执业药师,2013,10(4):34-38.
[2] 王彩霞,魏娜,毕宇鑫,等.酒石酸长春瑞滨脂质体的体内抗肿瘤作用研究[J].中国药学杂志,2013,48(20):1733-1736.
[3] 张兰风,孟凡迅,张金业,等.长春瑞滨渗漏后皮下注射解毒剂的实验研究[J].中国实用护理杂志,2005,21(7):325-327.
[4] 牛砚涛,董文娜,唐星,等.酒石酸长春瑞滨亚微乳注射液的稳定性[J].沈阳药科大学学报,2013,30(3):165-170.
[5] 王莉芳,王彩霞,魏娜,等.酒石酸长春瑞滨脂质体注射液的安全性及抗肿瘤作用研究[J].中国药理学通报,2012,28(11):1627-1628.
[6] 农春梅,雷小光.盐酸度洛西汀壳聚糖微球的制备与表征[J].西北药学杂志,2010,25(4):283-286.
[7] 张洪,沈瑶,闫士君,等.青蒿琥酯-壳聚糖纳米粒的制备及质量评价[J].中国医院药学杂志,2013,33(5):349-355.
[8] 马茜,范娟.壳聚糖纳米粒载体的应用研究进展[J].西北药学杂志,2015,30(2):213-215.
[9] Javia A,Thakkar H.Intranasal delivery of tapentadol hydrochloride-loaded chitosan nanoparticles:formulation,characterisation and its in vivo evaluation[J].J Microencaps,2017,34(7):644-658.
[10] Fazil M,Md S,Haque S,et al.Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting[J].Eur J Pharm Sci,2012,47(1):6-15.
[11] 颜承云,谷继伟,王曦,等.N-琥珀酰壳聚糖纳米粒肿瘤靶向性及抗肿瘤活性评价[J].中国现代应用药学,2010,27(10):868-873.
[12] Hu Y,Jiang X Q,Ding Y,et al.Synthesis and charaeterization of chitosan poly (aeryli acid) nanoparticles[J].Biomaterials,2002,23(15):3193-3201.
[13] Shikata F,Tokumitsu H,Iehikawa H,et al.In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capyure therapy of caneer[J].Eur J Pharm Biopharm,2002,53(1):57-63.
[14] 谢向阳,陈晨,林雯.重酒石酸长春瑞滨长循环脂质体的制备与表征[J].医药导报,2015,34(3):379-384.
[15] 郝吉福,房信胜,王建筑,等.应用Box-Behnken实验设计优化水飞蓟素固体脂质纳米粒处方研究[J].中草药,2011,42(11):2221-2225.
[16] 王子臣,赵文明.星点设计-效应面法优化制备吉非替尼壳聚糖鱼精蛋白纳米粒[J].中国新药杂志,2016,25(7):807-812.
[17] Lee D W,Marasini N,Poudel B K.Application of Box-Behnken design in the preparation and optimization of fenofibrate-loaded self-microemulsifying drug delivery system (SMEDDS)[J].J Microencaps,2014,31(1):31-40.
[18] Xie F,Ding R L,He W F.In vivo antitumor effect of endostatin-loaded chitosan nanoparticles combined with paclitaxel on Lewis lung carcinoma[J].Drug Deliv,2017,24(1):1410-1418.
[19] Sahin A,Yoyen-Ermis D,Caban-Toktas S.Evaluation of brain-targeted chitosan nanoparticles through blood-brain barrier cerebral microvessel endothelial cells[J].J Microencaps,2017,34(7):659-666.
[20] 张玮,张学农.壳聚糖纳米粒制备技术研究进展[J].抗感染药学,2008,5(2):65-69.
[21] 谢黎崖,柯金珍,陈月,等.壳聚糖纳米粒制备研究进展及在靶向给药系统中的应用[J].中国执业药师,2013,10(4):34-38.