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-閱讀頁
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【正文】 的藥時曲線，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。作為受體介導(dǎo)的腦內(nèi)遞藥系統(tǒng)，靶向頭基的成功連接是保證系統(tǒng)腦靶向性能的關(guān)鍵，因此我們通過多種方法證實了Lf在LfNP表面的成功連接。它生長迅速，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]。文獻(xiàn)報道載香豆素6的PLGA納米粒與細(xì)胞孵育2h后，游離香豆素6僅占細(xì)胞攝取香豆素6總量的3%[22]，我們進(jìn)行的體外泄露試驗也證實了24h內(nèi)香豆素6主要位于納米粒內(nèi)部。Garr233。Lf的這種進(jìn)入細(xì)胞核的能力可能會利于基因藥物的遞送。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]。因此，NP可以作為安全的對照組。統(tǒng)計學(xué)分析的結(jié)果表明，給予NP，Lf和LfNP后，各組細(xì)胞活力無顯著差異，體外證實了LfNP良好的安全性。致謝：。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, L214。, 2005, 2:108119.[17] LANGER R. Tissue engineering: a new field and its challenges [J]. Pharm Res, 1997, 14 (7):840–841.[18] ADAMS M L, LAVASANIFAR A, KWON G S. Amphiphilic block copolymers for drug delivery [J]. J Pharm Sci, 2003, 92(7):13431355.[19] LU W, ZHANG Y, TAN Y Z, et al. Cationic albuminconjugated pegylated nanoparticles as novel drug carrier for brain delivery [J]. J Control Release, 2005, 107:428448.[20] PEPPER M S, TACCHINICOTTIER F, SABAPATHY T K, MONTESANO R, WAGNER E F. Tumour Angiogenesis [M]. Oxford, UK: Oxford University Press, 1997:309331.[21] BROWN R C, MORRIS A P, O
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