乳鐵蛋白結(jié)合聚乙二醇聚乳酸納米粒腦內(nèi)遞藥特性-預(yù)覽頁(yè)
【正文】 素6可以作為熒光探針示蹤納米粒。 D Lf–NP only stained with 10nm colloidal gold labeled rabbit antigoat IgG。C，呈溫度依賴性（圖2A）。兩種納米粒的攝取呈時(shí)間，溫度和濃度依賴性，為主動(dòng)內(nèi)吞過(guò)程。C，給予相同濃度的LfNP和NP后， 細(xì)胞內(nèi)的熒光強(qiáng)度隨著時(shí)間的推移而增強(qiáng)，在30min，1h和2h， LfNP組的熒光均顯著強(qiáng)于NP組。C和4 186。C and 4 186。 C 10 μg/ml NP, Lf–NP and Lf–NP with 10 mg/ml Lf at 37 186。mA/I h；D/L h；B/J NP孵育1 h；E/M LfNP孵育1 h；C/K NP孵育2 h；F/N LfNP孵育2 hFig. 3 Fluorescent microscopy photographs of cells exposed to 15 μg/ml Lf–NP and NP at 37 186。 . n=3. LfNP腦內(nèi)遞藥特性的體內(nèi)評(píng)價(jià)小鼠大腦冰凍切片的熒光顯微鏡觀察結(jié)果表明在第三腦室室周區(qū)，皮層和紋狀體（圖 5B, D 和F）LfNP的分布顯著高于NP (圖5A, C和E)。Lf的引入增加了納米粒在腦內(nèi)的濃集，這可能是連接在表面的Lf通過(guò)其在BBB上的主動(dòng)轉(zhuǎn)運(yùn)增加了納米粒入腦。m.A periventricular region of the third ventricle after NP administration。 E striatum region after NP administration F striatum region after LfNP administration圖6小鼠尾靜脈注射60 mg/kg納米粒后血和腦中的香豆素6的藥時(shí)曲線，n=3Fig. 6 Blood and brain concentrationtime profiles of coumarin6 following . injection of coumarin6 loaded Lf–NP and NP at a dose of 60 mg/kg in mice. n=3.4. 討論粒徑大小直接影響微粒系統(tǒng)被腦毛細(xì)血管內(nèi)皮細(xì)胞內(nèi)吞的能力，通常用于腦內(nèi)遞藥的納米粒和脂質(zhì)體的粒徑都在200nm以下。它生長(zhǎng)迅速，多次傳代后仍能夠保持血腦屏障的性質(zhì)，形成功能性屏障且易于進(jìn)行多種分子生物學(xué)干涉，適宜作為血腦屏障的模型[21]。Garr233。PLA是一種公認(rèn)的低毒，生物相容且可降解的聚合物，被廣泛用于植入劑[26, 27]。統(tǒng)計(jì)學(xué)分析的結(jié)果表明，給予NP，Lf和LfNP后，各組細(xì)胞活力無(wú)顯著差異，體外證實(shí)了LfNP良好的安全性。REFERENCES[1] PARDRIDGE W M. Blood–brain barrier delivery [J]. Drug Discov Today, 2007, 12(1/2):5461.[2] PARDRIDGE W M. Drug targeting to the brain [J]. Pharm Res, 2007, 24(9): 17331744.[3] GARCIAGARCIA E, ANDRIEUX K, GILB S, et al. Colloidal carriers and blood–brain barrier (BBB) translocation: a way to deliver drugs to the brain? [J]. Int J Pharm, 2005, 298: 274292.[4] DE BOER A G, GAILLARD P J. Strategies to improve drug delivery across the bloodbrain barrier [J]. Clin Pharmacokinet, 2007, 46(7):553576.[5] CALVO P, GOURITIN B, CHACUN H, et al. Longcirculating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery [J]. Pharm Res, 2001, 18:11571166.[6] HUWYLER J, WU D F, PARDRIDGE W M. Brain drug delivery of small molecules using immunoliposomes [J]. P Natl Acad Sci USA, 1996, 93(24):1416414169.[7] ZHANG Y, CALON F, ZHU C, et al. Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism [J]. Hum Gene Ther, 2003, 14(1):112.[8] SHARMA A, SHARMA U. Liposomes in drug delivery: progress and limitations [J] Int J Pharm, 1997, 154:123140.[9] MOOS T, Morgan E H. Restricted transport of antitransferrin receptor antibody (OX26) through the bloodbrain barrier in the rat [J]. J Neurochem, 2001, 79(1):119129.[10] GOSK S, VERMEHREN C, STORM G, et al. Targeting antitransferrin receptor antibody (OX26) and OX26conjugated liposomes to brain capillary endothelial cells using in situ perfusion [J]. Cerebr Blood F Met, 2004, 24(11):11931204. [11] NUIJENS J H, VAN BERKEL P H C, SCHANBACHER F L. Structure and biological actions of lactoferrin [J]. Mammar Gland Biol, 1996, 1(3):285295.[12] FILLEBEEN C, DESCAMPS L, DEHOUCK M P, et al. Receptormediated transcytosis of lactoferrin through the bloodbrain barrier [J]. J Biol Chem, 1999, 274(11):70117017.[13] SUZUKI Y A, LOPEZ V, L2
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