|
|
Pharmacokinetics of rotenone loaded nanostructured lipid carriers and its modifiers in rats |
LI Ya-nan, MAO Quan-gao |
(Department of Pharmacy, the People′s Hospital of Rugao, Rugao Jiangsu 226500, China) |
|
|
Abstract [Abstract]Objective: To observe pharmacokinetical characterization of rotenone loaded nanostructured lipid carriers (RNLC) modified by polyethylene glycol(PEG) in rats. Methods:One hundred and twentythree SD rats were used in the serial tests. Twentyone rats were divided into three groups, each group were injected with rotenone solution, RNLC and PEG modified rotenone nanostructured lipid carriers (PEGRNLC), respectively. Blood were collected at different time points.The remaining 102 SD rats were randomly divided into 17 groups, 5 groups received subcutaneous injection of rotenone solution, 12 groups were given subcutaneous injection of RNLC(6 groups) and PEGRNLC(6 groups), respectively. Tissues of interests were harvested at different time points. HPLC was used to determine and the distribution of rotenone in blood and tissues of different groups were evaluated. Results:The AUC of rotenone solution in tissues from high to low in order was kidneys, liver, brain, spleen, heart and lung. Tmax of rotenone solution was 4 h in blood, while it was 8 h of RNLC and PEGRNLC. The AUC of RNLC and PEGRNLC was 35.99 and 42.03 times higher than rotenone solution respectively. The AUC of RNLC in tissues from high to low in order was brain, liver, kidneys, heart spleen, and lung. The contention of PEGRNLC in tissues was significantly increased in brain (substantia nigra and striatum) and decreased in the peripheral issues. Conclusion:PEGRNLC could increase the contention of rotenone in the striatum and substantia nigra, which further enhanced brain targeting of RNLC.
|
Received: 20 April 2016
|
|
|
|
[1]毛全高. 鱼藤酮PLGA纳米粒的制备及诱导大鼠帕金森病模型的实验研究\[J\]. 江苏大学学报:医学版,2016,26(1):82-87.[2]潘峰,孙玮,张晓庆,等. 高效液相色谱检测大鼠血浆鱼藤酮的含量\[J\]. 解放军预防医学杂志,2008,26(3):190-191.[3]杨媛,娄琨,梅兴国,等. 受体介导的脑靶向药物递送系统研究进展\[J\]. 中国药学杂志,2009,44(23):1761-1764.[4]田新华,魏峰,林晓宁. Tat聚乙二醇修饰明胶硅氧烷纳米粒跨血脑屏障研究\[J\]. 生物医学工程学杂志,2012,29(3):486-490,500.[5]Maaβen S, Schwarz C, Mehnert W, et al. Comparison of cytotoxicity between polyester nanoparticles and solid lipid nanoparticle(SLN)\[J\]. Proe Hit Symp Control Release Bioaxt Mater, 1993, 20(3): 490-491.[6]施斌,方超,游美羡,等. 聚乙二醇修饰对羟喜树碱隐形纳米囊泡的肿瘤靶向和抑瘤作用的影响\[J\]. 中国临床药学杂志,2006,15(1):46-49.[7]胡永祥,牛津梁,张文博,等. 聚乙二醇修饰药物技术的研究进展\[J\]. 中国生化药物杂志,2004,25(6):369-373.[8]施险峰,詹家荣,廖本仁. 聚乙二醇修饰技术研究进展\[J\].上海化工,2007,32(12):30-32.[9]黄萍,崔纯莹,王玉记,等. 聚乙二醇包裹表阿霉素脂质体的制备及评价\[J\]. 首都医科大学学报,2015,36(2):166-171.[10]王蕾蕾. 黄体酮脂质纳米粒的制备及其生物利用度研究\[D\]. 杭州:浙江大学,2007.[11]张馨欣,甘勇,杨星钢,等. 聚乙二醇修饰的羟基喜树碱纳米脂质载体的制备及其小鼠组织分布\[J\]. 药学学报,2008,43(1):91-96.[12]耿良,杨彩玲,田同德,等. 人参皂苷Rg3和PEGPLGARg3纳米微粒对人血管内皮细胞侵袭和微管形成能力的影响\[J\]. 北京中医药大学学报,2014,37(9):611-615.[13]Mosqueira VC, Legrand P, Gref R, et al. Interactions between a macrophage cell line(J774A1) and surfacemodified poly(D,Llactide) nanocapsules bearing poly(ethylene glycol)\[J\]. J Drug Target, 1999, 7(1): 65-78.[14]金英华. 纳米粒的靶向修饰研究进展\[J\]. 医药导报,2007,26(12):1473-1476.[15]Kaur IP, Bhandari R, Bhandari S, et al. Potential of solid lipid nanoparticles in brain targeting\[J\]. J Controlled Release, 2008, 127(2): 97-109.[16]Zara GP,Cavalli R,Bargoni A,et al. Intravenous administration to rabbits of nonstealth and stealth doxorubicinloaded solid lipid nanoparticles at increasing concentrations of stealth agent: pharmacokinetics and distribution of doxorubicin in brain and other tissues\[J\]. J Drug Target, 2002, 10(4): 327-335.[17]Calvo P, Gouritin B, Brigger I , et al. PEGylated polycyanoacrylate nanoparticles as vector for drug delivery in prion diseases\[J\]. J Neurosci Methods, 2001, 111(2): 151-155.[18]刘梅,王莉,胡凯莉,等. 人参皂苷Rg1经PEG修饰前后的组织分布研究\[J\]. 中国中药杂志,2012,37(12):1747-1750. |
|
|
|