乳铁蛋白修饰水飞蓟素纳米乳的制备及其大鼠体内药代动力学
Preparation of lactoferrin-modified silymarin nanoemulsion and its pharmacokinetics in rats
-
摘要: 采用磷脂/吐温80体系制备普通水飞蓟素纳米乳(SM-NE)，通过静电作用在其表面吸附乳铁蛋白得到乳铁蛋白修饰的水飞蓟素纳米乳(LF-SM-NE)，分别考察两者包封率、形态、粒径、Zeta电位，随后采用LC-MS/MS测定经口给药后大鼠体内的吸收情况。研究结果显示，当乳铁蛋白浓度为0.15 mg/mL，温孵时间为4 h时，乳铁蛋白在SM-NE表面的吸附趋于饱和，所得LF-SM-NE外观圆整呈类球状，平均粒径(257±5.9)nm，Zeta电位-(33.1±1.5)mV，包封率为(96.9±1.9)%，载药量为(3.90±0.12)%；与普通水飞蓟素纳米乳相比，经LF修饰后的SM-NE在大鼠体内的药物浓度显著增高，cmax和AUC均提高约2倍左右。因此，经LF修饰后的SM-NE可进一步提高药物的在体内吸收，是一种新型纳米粒口服吸收增强技术，具有良好的应用潜能。Abstract: In this paper, silymarin nanoemulsions(SM-NE)were prepared based upon PC/Tween 80 system, and adsorption of lactoferrin(LF)absorbed onto the surface of silymarin nanoemulsions via electrostatic interaction resulted in the formation of lactoferrin-modified silybin nanoemulsions(LF-SM-NE). SM-NE and LF-SM-NE were characterized in terms of the shape, diameter, zeta potential, and entrapment efficiency. In addition, in vivo absorption of SM-NE and LF-SM-NE following oral dosing was investigated by the application of LC-MS/MS in the determination of silymarin in blood sample. The results showed that the saturated adsorption of Lf at the surface of the SM-NE occurred at LF concentration of 0. 15 mg/mL and the incubation time of 4 h. LF-SM-NE were spherical with average particle size of(257±5. 9)nm, zeta potential of -(33. 1±1. 5)mV, entrapment efficiency(96. 9±1. 9)% and drug loading(3. 90±0. 12)%. Compared with those of SM-NE, LF-SM-NE significantly increased drug levels of LF in rats were observed after dosing of LF-SM-NE, and both of cmax and AUC were increased by approximately 2-fold. In summary, LF-SM-NE could improve oral drug absorption of LF in rats. The approach of enhancement in oral absorption of the nanoemulsions shows a promise for the application.
-
Keywords:
- silymarin /
- lactoferrin /
- nanoemulsion /
- bioavailability /
- absorption enhancer
-
-
[1] Liu ZG,Li XL,Weng LD,et al.Research progress in pharmacological effects of silymarin[J].J Liaoning Univ TCM(辽宁中医药大学学报),2012,14(10):91-93. [2] Zhuang SS,Chen JM,Wang WY,et al.Research on improving bioavailability of silymarin by new technology[J].Chin J Hosp Pharm(中国医院药学杂志),2014,34(24):2158-2161. [3] Parveen R,Baboota S,Ali J,et al.Effects of silymarin nanoemulsion against carbon tetrachloride-induced hepatic damage[J].Arch Pharm Res,2011,34(5):767-774. [4] Yuan H.Study on gastrointestinal transport of solid lipid nanoparticles by oral drug carrier(固体脂质纳米粒口服药物载体经胃肠道转运的研究)[D].Hangzhou:Zhejiang University,2008. [5] Shofner JP,Phillips MA,Peppas NA.Cellular evaluation of synthesized insulin/transferrin bioconjugates for oral insulin delivery using intelligent complexation hydrogels[J].Macromol Biosci,2010,10(3):299-306. [6] Amet N,Wang W,Shen WC.Human growth hormone-transferrin fusion protein for oral delivery in hypophysectomized rats[J].J Control Release,2010,141(20):177-182. [7] Chinese Pharmacopeia Commission.WS-10001-(HD-0600)-2002,National Drug Standards for Chemicals Promoted from Local Standards.Vol 7(国家药品标准:化学药品地方标准上升国家标准.第七册)[S].Beijing:China Medical Science Press,2002:30-31. [8] Luo XJ,Li W,Han JP,et al.HPLC-MS/MS study on pharmacokinetics of silybin A and silybin B in rat plasma[J].Chin J Pharm Anal(药物分析杂志),2009,29(12):2002-2006. [9] Chen HL,Wu MJ,Wang X,et al.Construction and characterization of lactoferrin modified procationic liposomes[J].Central South Pharm(中南药学),2010,8(2):81-84. [10] Xiao YY,Chen X,Zou L,et al.Preparation of lactoferrin-modified nanostructured lipid carriers and evaluation of its brain targeting efficiency[J].Chin Pharm J(中国药学杂志),2013,48(20),1755-1760. [11] Yang J,Xie J.Determination of lyso-phosphatidylcholine and lyso-phosphatidylethanolamine in docetaxel concentrated Solution for Injection[J].Chin J Mod Appl Pharm(中国现代应用药学),2013,30(11):1210-1214.
计量
- 文章访问数: 1073
- HTML全文浏览量: 1
- PDF下载量: 2029
下载:
