橙皮苷纳米乳液的制备及其稳定性研究
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摘要
目的制备以甘草酸作为乳化剂的橙皮苷纳米乳液(HDN-NE),以期开发橙皮苷的新型绿色纳米制剂。方法采用高速剪切-高压均质技术制备HDN-NE,以粒径、PDI、外观为主要评价指标筛选处方工艺,对以最佳处方工艺制备的HDN-NE的理化性质和相关稳定性进行研究。结果 HDN-NE的最佳制备处方为橙皮苷用量0.1%、甘草酸用量0.3%、油相用量5%,最佳工艺参数为剪切速率13000r/min、剪切时间2min、均质压力100MPa、均质次数6次;制得纳米乳平均粒径为(262.7±3.1)nm、PDI为0.234±0.009、Zeta电位为(-35.42±0.72)m V、溶解度(460.3±2.1)μg/m L、电导率(116.4±1.7)μs/cm、pH值为6.820±0.008、浊度为451 cm-1(n=3);经染色法鉴别为O/W乳液,透射电镜观察乳滴呈圆球状,大小均一;稳定性研究结果表明HDN-NE稳定性良好。结论以甘草酸作为乳化剂的HDN-NE可显著提高橙皮苷的溶解度及稳定性,是一种潜在的安全性高的新型纳米药物。
Objective To prepare a new hesperidin nanoemulsion(HDN-NE) with glycyrrhizic acid as emulsifier, by which could develop a "new green nano-pharmaceutics" of hesperidin. Methods HDN-NE was prepared by high-speed shearing and high-pressure homogenization. The prescription of HDN-NE was optimized with particle size, PDI, and appearance as indexes. The physicochemical property and stability of HDN-NE prepared by the optimal prescription were studied. Results The optimal prescription of HDN-NE was as follow: The content of hesperidin, glycyrrhizic acid, and oil phase were 0.1%, 0.3%, and 5%,respectively. The shear rate was 13 000 r/min, the cutting time was 2 min, the homogeneous pressure and times were 100 MPa and 6,severally. The result showed that the prepared HDN-NE had the mean size of(262.7 ± 3.1) nm, PDI of 0.234 ± 0.009, Zeta potential of(-35.42 ± 0.72) mV, and solubility of(460.3 ± 2.1) μg/mL. The physicochemical property study showed that the conductivity was(116.4 ± 1.7) μs/cm, the pH was 6.820 ± 0.008, and the turbidity was 451 cm-1(n = 3). It was identified as O/W emulsion by dyeing method. The droplets were spherical and uniform by transmission electron microscopy. The stability study showed that HDN-NE had good stability. Conclusion HDN-NE with glycyrrhizic acid as an emulsifier can significantly improve the solubility and stability of hesperidin, which is a new potential nano-drug with safety.
Objective To prepare a new hesperidin nanoemulsion(HDN-NE) with glycyrrhizic acid as emulsifier, by which could develop a "new green nano-pharmaceutics" of hesperidin. Methods HDN-NE was prepared by high-speed shearing and high-pressure homogenization. The prescription of HDN-NE was optimized with particle size, PDI, and appearance as indexes. The physicochemical property and stability of HDN-NE prepared by the optimal prescription were studied. Results The optimal prescription of HDN-NE was as follow: The content of hesperidin, glycyrrhizic acid, and oil phase were 0.1%, 0.3%, and 5%,respectively. The shear rate was 13 000 r/min, the cutting time was 2 min, the homogeneous pressure and times were 100 MPa and 6,severally. The result showed that the prepared HDN-NE had the mean size of(262.7 ± 3.1) nm, PDI of 0.234 ± 0.009, Zeta potential of(-35.42 ± 0.72) mV, and solubility of(460.3 ± 2.1) μg/mL. The physicochemical property study showed that the conductivity was(116.4 ± 1.7) μs/cm, the pH was 6.820 ± 0.008, and the turbidity was 451 cm-1(n = 3). It was identified as O/W emulsion by dyeing method. The droplets were spherical and uniform by transmission electron microscopy. The stability study showed that HDN-NE had good stability. Conclusion HDN-NE with glycyrrhizic acid as an emulsifier can significantly improve the solubility and stability of hesperidin, which is a new potential nano-drug with safety.
引文
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[22]姚艳玉,马培华,曾庆晗,等.油相种类对姜黄素纳米乳液稳定性的影响[J].食品科技,2017,42(9):238-242.
[23]鲁丁丁.甜橙油纳米乳的构建及其稳定性研究[D].杭州:浙江工商大学,2015.
[2]Ma Y,Ye X,Hao Y,et al.Ultrasound-assisted extraction of hesperidin from Penggan(Citrus reticulata)peel[J].Ultrason Sonochem,2008,15(3):227-232.
[3]Inoue T,Tsubaki S,Ogawa K,et al.Isolation of hesperidin from peels of thinned Citrus unshiu fruits by microwave-assisted extraction[J].Food Chem,2010,123(2):542-547.
[4]徐玉玲,伍利华,李鹏程,等.基于橙皮苷临床利用量的青皮品质评价研究[J].中草药,2016,47(22):4009-4015.
[5]Kalpana K B,Devipriya N,Srinivasan M,et al.Evaluating the radioprotective effect of hesperidin in the liver of Swiss albino mice[J].Eur J Pharmacol,2011,658(2/3):206-212.
[6]Martínez A L,González-Trujano M E,Chávez M,et al.Hesperidin produces antinociceptive response and synergistic interaction with ketorolac in an arthritic gout-type pain in rats[J].Pharmacol Biochem Be,2011,97(4):683-689.
[7]Park H J,Kim M J,Ha E,et al.Apoptotic effect of hesperidin through caspase 3 activation in human colon cancer cells,SNU-C4[J].Phytomedicine,2008,15(1/2):147-151.
[8]Ahmad S T,Arjumand W,Nafees S,et al.Hesperidin alleviates acetaminophen induced toxicity in wistar rats by abrogation of oxidative stress,apoptosis and inflammation[J].Toxicol Lett,2012,208(2):149-161.
[9]刘本国,张瑞婷,吴晓楠,等.橙皮苷/羟丙基-β-环糊精包合物的理化性质研究[J].现代食品科技,2013,29(10):2349-2352.
[10]橙皮苷自微乳的制备与评价[D].合肥:安徽医科大学,2011.
[11]李文华,王英姿,骆声秀,等.苦参总碱纳米乳和苦参总碱纳米乳凝胶的透皮机制研究[J].中草药,2017,48(3):484-489.
[12]徐婷.柠檬醛纳米乳状液的制备及稳定机理研究[D].上海:上海应用技术大学,2016.
[13]张宽云,马燕.紫杉醇-油酸和鸦胆子油分子配型组装纳米乳给药系统研究[J].中草药,2017,48(8):1544-1552.
[14]Gü?lü-üstünda??,Mazza G.Saponins:Properties,applications and processing[J].Crit Rev Food Sci,2007,47(3):231-258.
[15]王宇光,史新元,乔延江.剪切作用对甘草皂苷胶束聚集形态影响的介观模拟研究[J].世界科学技术-中医药现代化,2012,14(1):1201-1205.
[16]Ding H,Yin Q,Wan G,et al.Solubilization of menthol by platycodin D in aqueous solution:An integrated study of classical experiments and dissipative particle dynamics simulation[J].Int J Pharmacol,2015,480(1/2):143-151.
[17]Tolstikova T G,Khvostov M V,Bryzgalov A O.The complexes of drugs with carbohydrate-containing plant metabolites as pharmacologically promising agents[J].Mini-Rev Med Chem,2009,9(11):1317-1328.
[18]Radwan M A,Aboul-Enein H Y.The effect of oral absorption enhancers on the in vivo performance of insulin-loaded poly(eth-ylcyanoacrylate)nanospheres in diabetic rats[J].J Microencapsul,2002,19(2):225-235.
[19]夏鹏飞,马肖,吴国泰,等.龙胆苦苷纳米乳处方优化及其质量评价[J].中国中医药信息杂志,2018,25(7):62-66.
[20]Justyna F,Marie A B,Jocelyne P,et al.Topical delivery of lipophilic drugs from O/W Pickering emulsions[J].Int J Pharmacol,2009,371:56-63.
[21]Song M G,Cho S H,Kim J Y,et al.Novel evaluation method for the water-in-oil(W/O)emulsion stability by turbidity ratio measurements[J].Korean J Chem Eng,2002,19(3):425-430.
[22]姚艳玉,马培华,曾庆晗,等.油相种类对姜黄素纳米乳液稳定性的影响[J].食品科技,2017,42(9):238-242.
[23]鲁丁丁.甜橙油纳米乳的构建及其稳定性研究[D].杭州:浙江工商大学,2015.