乳鐵蛋白結(jié)合聚乙二醇聚乳酸納米粒腦內(nèi)遞藥特性doc(參考版)
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【正文】 NEIL R G. Tight junction protein expression and barrier properties of immortalized mouse brain microvessel endothelial cells [J]. Brain Res, 2007, 1130:1730.[22] DESAI M P, LABHASETWAR V, WALTER E, et al. The mechanism of uptake of biodegradable microparticles in Caco2 cells is size dependent [J]. Pharm Res, 1997, 14:15681573.[23] GRAU A J, WILLG V, FOGEL W, et al. Assessment of Plasma Lactoferrin in Parkinson’s Disease [J]. Movement Disord, 2001, 16(1):131134.[24] FAUCHEUX B A, NILLESSE N, DAMIER P, et al. Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease [J]. Proc Natl Acad Sci USA Neurobiology, 1995, 92:96039607. [25] KAWAMATA T, TOOYAMA I, YAMADA T, et al. Lactotransferrin immunocytochemistry in Alzheimer and normal human brain [J] Am J Pathol, 1993, 142(5):15741585.[26] PLARD J P, BAZILE D. Comparison of the safety profiles of PLA50 and –PLA50 nanoparticles after single dose intravenous administration to rats [J]. Colloid Surface B, 1999, 16:173183.[27] MATSUSUE Y, HANAFUSA S, YAMANURO T, et al. Tissue reaction of bioabsorbable ultra high strength poly (l–lactide) rod. A longterm study in rabbits [J]. Clin Orthop, 1995, 317:246253.[28] ZAMBAUX M F, BONNEAUX F, GREF R, et al. Protein Cloaded monomethoxypoly (ethylene oxide) –poly(lactic acid) nanoparticles [J]. Int J Pharm, 2001, 212:19.[29] THOTATHIL Z, JAMESON M B. Early experience with novel immunomodulators for cancer treatment [J]. Expert Opin Inv Drug, 2007, 16(9):13911403.[30] TOMITA M, WAKABAYASHI H, YAMAUCHI K, et al. Bovine lactoferrin and lactoferricin derived from milk: production and applications [J]. Biochem Cell Biol, 2002, 80(1) :109112.16 / 16。NNERDAL B. Mammalian lactoferrin receptors: structure and function [J]. Cell Mol Life Sci, 2005, (62):25602575.[14] HUANG R Q, KE W L, QU Y H, et al. Characterization of lactoferrin receptor in brain endothelial capillary cells and mouse brain [J]. J Biomed Sci, 2007, 14:121128.[15] JI B, MAEDA J, HIGUCHI M. Pharmacokinetics and brain uptake of lactoferrin in rats [J]. Life Sci, 2006, 78:851855.[16] OLIVIER J C. Drug transport to brain with targeted nanoparticles [J]. NeuroRx174。感謝復(fù)旦大學(xué)的趙慧玲老師和戴維林老師指導(dǎo)進(jìn)行了TEM和XPS的分析。然而，其體內(nèi)毒性和長期毒性還有待進(jìn)一步考察。臨床研究證實(shí)了Lf的安全性[29, 30]。此外，PEG的毒性也很低[28]。有文獻(xiàn)報(bào)道在某些病理?xiàng)l件下（如帕金森病和Alzheimer’s?。㎜f受體在腦內(nèi)的表達(dá)量會(huì)增加[2325]，雖然這種現(xiàn)象的機(jī)理還沒有明確，我們卻可以借助Lf的這種性質(zhì)利用LfNP更好的治療這些疾病在進(jìn)行新型藥物傳遞系統(tǒng)開發(fā)過程中，一個(gè)非常重要的方面就評(píng)價(jià)其生物相容性和對于靶細(xì)胞的毒性，對于腦內(nèi)遞藥系統(tǒng)更是如此。的研究表明被K562髓性白血病細(xì)胞攝取后的Lf可以進(jìn)入細(xì)胞核并與DNA結(jié)合，Nuijens等人的研究也表明Lf可能具有調(diào)節(jié)基因表達(dá)的功能，這與我們觀察到LfNP在細(xì)胞核中的分布相一致。因此，我們認(rèn)為測得細(xì)胞中的香豆素6主要反應(yīng)了包載其的納米粒的分布情況。因此。,它具有多種內(nèi)皮細(xì)胞的性質(zhì):表達(dá)von Willebrand因子,具有血管內(nèi)皮生長因子受體并可以內(nèi)吞乙?；牡兔芏戎鞍椎萚20]。本文采用Lf構(gòu)建的新型生物可降解腦內(nèi)遞藥系統(tǒng)LfNP粒徑在150nm以下，適宜用于腦內(nèi)遞藥。 D cortex after LfNP administration。 B periventricular region of the third ventricle after LfNP administration。mA給予NP后的第三腦室室周區(qū)；B 給予LfNP后的第三腦室室周區(qū)；C 給予NP后的大腦皮質(zhì)；D給予LfNP后的大腦皮質(zhì)；E 給予NP后的紋狀體區(qū)域；F給予LfNP后的紋狀體區(qū)域Fig. 5 Distribution of NP and Lf–NP in mouse brain after . 60 mg/kg nanoparticles in mouse caudal vein, visualized using the FITC filter 1h. The magnification bar is 50 181。給予LfNP和NP后，血中的香豆素6濃度沒有顯著差異，說明少量Lf連接在納米粒表面并不影響PEG的長循環(huán)功能。
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