半乳糖介导姜黄素牛血清白蛋白纳米粒的制备及质量评价
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摘要
目的建立去溶剂法制备半乳糖介导的姜黄素白蛋白纳米粒,并考察其理化性质及体外释药特性。方法以半乳糖修饰的牛血清白蛋白作为载体材料,姜黄素作为模型药物,采用去溶剂法制备姜黄素半乳糖化白蛋白纳米粒,单因素考察优化处方工艺,采用激光纳米粒度仪对其粒径和Zeta电位进行测定;超速离心法测定包封率及载药量;透析法考察其体外释药特性。结果根据优化处方工艺制备的白蛋白纳米粒外观呈圆形或类圆形,粒径分布为(267.1±78.3) nm,Zeta电位为-40～-50 mV;包封率为79.4%,载药量为3.7%;姜黄素纳米粒在8 h释药量为20%,48 h释药量>80%。结论去溶剂法制备的姜黄素纳米粒具有良好的理化性质和释药性能,提高药物的稳定性,可显著提高药物释放速率,提高生物利用度。
Objective To prepare galactosylated bovine serum albumin nanoparticles(Gal-BSA NPs) of curcumin by desolvation method, and to investigate its physicochemical properties and in vitro release characteristics. Methods Gal-BSA NPs were prepared by emulsion solvent evaporation method, and the preparation processes was optimized. Its size and Zeta potential were measured by Laser size and Zeta potential instrument. Entrapment efficiency and drug loading were measured by ultracentrifugation. The in vitro release characteristics were investigated by dialysis method. Results According to the preparation of the formulation and process optimization, the appearance of Gal-BSA NPs prove to be round or oval, particle size distribution was(267.1±78.3) nm, Zeta potential was-40 to-50 mV. Entrapment efficiency was 79.4%, and drug loading was 3.7%. Gal-BSA NPs release 20% at 8 h and >80% at 48 h. Conclusion Solvent evaporation method can successfully prepare Gal-BSA NPs, and shows good physical and chemical properties and release properties, improve the stability of the drug, and can prolong the drug release rate and improve the bioavailability.
Objective To prepare galactosylated bovine serum albumin nanoparticles(Gal-BSA NPs) of curcumin by desolvation method, and to investigate its physicochemical properties and in vitro release characteristics. Methods Gal-BSA NPs were prepared by emulsion solvent evaporation method, and the preparation processes was optimized. Its size and Zeta potential were measured by Laser size and Zeta potential instrument. Entrapment efficiency and drug loading were measured by ultracentrifugation. The in vitro release characteristics were investigated by dialysis method. Results According to the preparation of the formulation and process optimization, the appearance of Gal-BSA NPs prove to be round or oval, particle size distribution was(267.1±78.3) nm, Zeta potential was-40 to-50 mV. Entrapment efficiency was 79.4%, and drug loading was 3.7%. Gal-BSA NPs release 20% at 8 h and >80% at 48 h. Conclusion Solvent evaporation method can successfully prepare Gal-BSA NPs, and shows good physical and chemical properties and release properties, improve the stability of the drug, and can prolong the drug release rate and improve the bioavailability.
引文
[1] PANCHAL H D,VRANIZAN K,LEE C Y,et al.Early anti-oxidative and anti-proliferative curcumin effects on neuroglioma cells suggest therapeutic targets[J].Neurochem Res,2008,3(9):1701-1710.
[2] 孙永,彭明利.姜黄素及其衍生物在肝脏相关疾病中防治作用的研究进展[J].药学学报,2014,49(11):1483-1490.
[3] 隋菱,郑静彬,蔡国弟,等.姜黄素对四氯化碳诱导大鼠急性肝损害的保护作用[J].中国现代应用药学,2017,34(11):1517-1521.
[4] 李旭炯,刘安,陈云霞,等.姜黄素对肝肺综合征大鼠的保护作用[J].中国临床药理学与治疗学,2017,22(7):738-742.
[5] 徐步远,潘显阁,陈崇别,等.姜黄素对Lewis肺癌小鼠血管内皮成长因子和endostatin表达的影响[J].中国临床药理学与治疗学,2017,22(2):151-154.
[6] UM Y,CHO S,WOO H,et al.Synthesis of curcumin mimics with multidrug resistance reversal activities [J].Bioorg Med Chem,2008,16(7):3608-3615.
[7] KURIEN B T,SINGH A,MATSUMOTO H,et al.Improving the solubility and pharmacological efficacy of curcumin by heat treatment [J].Assay Drug Dev Technol,2007,5(4):567-576.
[8] WANG Y J,PAN M H,CHENG A L,et al.Stability of curcumin in buffer solutions and characterization of its degradation products [J].J Pharm Biomed Anal,1997,15(12):1867-1876.
[9] 陈晓红,迟宗良,秦昆明,等.姜黄素-赖氨酸共晶在无水乙醇中的热力学研究[J].中国现代应用药学,2017,34(6):871-875.
[10] 高会乐,蒋新国.肿瘤靶向递药新策略的研究进展[J].药学学报,2016,51(2):272-280.
[11] 戴东波,尤佳何,雯洁,等.姜黄素聚乙二醇-聚乳酸嵌段共聚物纳米粒的制备及其质量评价[J].中草药,2014,45(2):194-199.
[12] ELZOGHBY A O,SAMY W M,ELGINDY N A.Albumin-based nanoparticles as potential controlled release drug delivery systems[J].J Control Release,2012,157(2):168-182.
[13] LI C,ZHANG D,GUO H,et al.Preparation and characteri-zation of galactosylated bovine serum albumin nanoparticles for liver-targeted delivery of oridonin[J].Int J Pharm,2013,448(1):79-86.
[10] GAO S,SUN J,FU D,et al.Preparation,characterization and pharmacokinetic studies of tacrolimus-dimethyl-cyclodextrin inclusion complex-loaded albuminnanoparticles [J].Int J Pharm,2012,4(27):410-416.
[11] 潘艺茗,黄岳山.聚乳酸/聚乙二醇琥珀酸酯-姜黄素纳米粒的制备及体外评价[J].中国组织工程研究,2012,16(3):421-425.
[12] 李然,赵燕娜,王婷,等.基于新型树枝状大分子姜黄素纳米粒的制备及体外释放[J].医药导报,2017,36(5):538-543.
[13] 徐红,张成鸿,关欣,等.槲皮素PLGA-TPGS纳米粒的质量考察[J].医药导报,2017,36(10):1182-1186.
[14] 艾凤伟,庄海涛,凌勇,等.星点设计-效应面法优化青蒿素微囊的制备工艺[J].中成药,2015,37(7):1457-1461.
[2] 孙永,彭明利.姜黄素及其衍生物在肝脏相关疾病中防治作用的研究进展[J].药学学报,2014,49(11):1483-1490.
[3] 隋菱,郑静彬,蔡国弟,等.姜黄素对四氯化碳诱导大鼠急性肝损害的保护作用[J].中国现代应用药学,2017,34(11):1517-1521.
[4] 李旭炯,刘安,陈云霞,等.姜黄素对肝肺综合征大鼠的保护作用[J].中国临床药理学与治疗学,2017,22(7):738-742.
[5] 徐步远,潘显阁,陈崇别,等.姜黄素对Lewis肺癌小鼠血管内皮成长因子和endostatin表达的影响[J].中国临床药理学与治疗学,2017,22(2):151-154.
[6] UM Y,CHO S,WOO H,et al.Synthesis of curcumin mimics with multidrug resistance reversal activities [J].Bioorg Med Chem,2008,16(7):3608-3615.
[7] KURIEN B T,SINGH A,MATSUMOTO H,et al.Improving the solubility and pharmacological efficacy of curcumin by heat treatment [J].Assay Drug Dev Technol,2007,5(4):567-576.
[8] WANG Y J,PAN M H,CHENG A L,et al.Stability of curcumin in buffer solutions and characterization of its degradation products [J].J Pharm Biomed Anal,1997,15(12):1867-1876.
[9] 陈晓红,迟宗良,秦昆明,等.姜黄素-赖氨酸共晶在无水乙醇中的热力学研究[J].中国现代应用药学,2017,34(6):871-875.
[10] 高会乐,蒋新国.肿瘤靶向递药新策略的研究进展[J].药学学报,2016,51(2):272-280.
[11] 戴东波,尤佳何,雯洁,等.姜黄素聚乙二醇-聚乳酸嵌段共聚物纳米粒的制备及其质量评价[J].中草药,2014,45(2):194-199.
[12] ELZOGHBY A O,SAMY W M,ELGINDY N A.Albumin-based nanoparticles as potential controlled release drug delivery systems[J].J Control Release,2012,157(2):168-182.
[13] LI C,ZHANG D,GUO H,et al.Preparation and characteri-zation of galactosylated bovine serum albumin nanoparticles for liver-targeted delivery of oridonin[J].Int J Pharm,2013,448(1):79-86.
[10] GAO S,SUN J,FU D,et al.Preparation,characterization and pharmacokinetic studies of tacrolimus-dimethyl-cyclodextrin inclusion complex-loaded albuminnanoparticles [J].Int J Pharm,2012,4(27):410-416.
[11] 潘艺茗,黄岳山.聚乳酸/聚乙二醇琥珀酸酯-姜黄素纳米粒的制备及体外评价[J].中国组织工程研究,2012,16(3):421-425.
[12] 李然,赵燕娜,王婷,等.基于新型树枝状大分子姜黄素纳米粒的制备及体外释放[J].医药导报,2017,36(5):538-543.
[13] 徐红,张成鸿,关欣,等.槲皮素PLGA-TPGS纳米粒的质量考察[J].医药导报,2017,36(10):1182-1186.
[14] 艾凤伟,庄海涛,凌勇,等.星点设计-效应面法优化青蒿素微囊的制备工艺[J].中成药,2015,37(7):1457-1461.