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-展示頁(yè)
2024-08-01 16:00本頁(yè)面
【正文】 。 Biodegradable nanoparticle。 Blood–brain barrier (BBB)。結(jié)論 LfNP能顯著增加藥物的腦內(nèi)遞送且具有較好的生物相容性，有望作為一種新型的腦內(nèi)遞送系統(tǒng)輸送蛋白多肽和基因等大分子藥物入腦。靜脈注射載香豆素6的納米粒后，LfNP組小鼠腦內(nèi)香豆素6的量約為NP組的3倍。免疫電鏡技術(shù)，X射線光電子能譜分析及酶聯(lián)免疫吸附試驗(yàn)證實(shí)了LfNP表面共價(jià)連接有Lf，且每個(gè)LfNP表面的Lf數(shù)約為55。利用熒光顯微技術(shù)和冷凍切片技術(shù)觀察小鼠尾靜脈注射載香豆素6的LfNP后的腦內(nèi)分布情況并進(jìn)行了藥動(dòng)學(xué)研究。采用透射電鏡技術(shù)，免疫電鏡技術(shù)，動(dòng)態(tài)光散射分析，X射線光電子能譜分析及酶聯(lián)免疫吸附試驗(yàn)對(duì)LfNP的形態(tài),粒徑和表面Lf的連接進(jìn)行鑒定和表征。乳鐵蛋白結(jié)合聚乙二醇聚乳酸納米粒腦內(nèi)遞藥特性的體內(nèi)外研究胡凱莉，李靖煒，沈燁虹, 陸偉，高小玲, 蔣新國(guó)基金項(xiàng)目：國(guó)家973項(xiàng)目“導(dǎo)向性納米載藥系統(tǒng)及其腦部疾病治療與診斷中的應(yīng)用基礎(chǔ)研究”作者簡(jiǎn)介：胡凱莉，女，博士研究生 通訊作者：蔣新國(guó)，男，研究員，博士生導(dǎo)師 Tel: (021)54237381 Email: xgjiang （復(fù)旦大學(xué)藥學(xué)院藥劑教研室，上海 200032）摘要：目的 構(gòu)建一種新型可生物降解腦內(nèi)遞藥系統(tǒng)乳鐵蛋白結(jié)合聚乙二醇聚乳酸納米粒（LfNP），并對(duì)其腦內(nèi)遞藥特性進(jìn)行體內(nèi)外評(píng)價(jià)。 方法 采用馬來酰亞胺基聚乙二醇聚乳酸和甲氧基聚乙二醇聚乳酸通過復(fù)乳溶劑揮發(fā)法制備納米粒（NP）,將其與巰基化的乳鐵蛋白（Lf）共價(jià)連接制得LfNP。采用CCK8評(píng)價(jià)了LfNP對(duì)細(xì)胞活力的影響。 結(jié)果 制得的LfNP形態(tài)圓整，粒徑在110 nm左右。℃，不同濃度和不同孵育時(shí)間條件下均顯著高于未結(jié)合納米粒（NP）。3 mg/。關(guān)鍵詞：乳鐵蛋白；血腦屏障；香豆素6；生物可降解納米粒；腦內(nèi)遞送中圖分類號(hào)：R9 Lactoferrinconjugated PEG–PLA nanoparticles with improved brain delivery: in vitro and in vivo evaluationsHU Kaili, LI Jingwei, SHEN Yehong, LU Wei, GAO Xiaoling, Jiang Xinguo (Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032)ABSTRACT：OBJECTIVE To construct the lactoferrin (Lf) conjugated poly (ethyleneglycol) –poly (lactide) (PEG–PLA) nanoparticle (Lf–NP) as a novel biodegradable brain drug delivery system and evaluate its in vitro and in vivo delivery properties. METHODS Lf was thiolated and conjugated to the distal maleimide functions surrounding on the pegylated nanoparticles prepared by double emulsion and solvent evaporation procedure to form the Lf–NP. Dynamic light scattering analysis, transmission electron micrograph (TEM), Xray photoelectron spectrometry analysis and ELISA were used to characterize the LfNP. A fluorescent probe, coumarin6 was incorporated into Lf–NP and its uptake by a mouse brain capillary endothelial cell line, were pared to that of unconjugated nanoparticle (NP). The brain distribution of LfNP following an intravenous administration was evaluated quantitatively by pharmacokinetic studies and qualitatively by fluorescent microscopy. The influence of LfNP on cell viability was also evaluated. RESULTS Dynamic light scattering analysis and transmission electron micrograph (TEM) showed that the Lf–NP had a round and regular shape with an average diameter of around 110 nm. The existence of Lf on the surface of Lf–NP was verified by TEM observation and Xray photoelectron spectrometry analysis. The Lf ELISA results confirmed the biorecognitive activity of Lf after the covalent coupling procedure and suggested the average number of Lf conjugated on each nanoparticle was around 55. The uptake of Lf–NP by was shown significantly higher than that of NP at 37 ℃, at different concentrations and incubation times. Following an intravenous administration of a dose of 60mg/kg in mice caudal vein, a near 3 folds of coumarin6 were found in the mice brain carried by Lf–NP pared to that carried by NP. Cell viability experiment results confirmed good safety of the biodegradable Lf–NP. CONCLUSION The significant in vitro and in vivo results suggested that Lf–NP is a promising brain drug delivery s
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