Targeting delivery of simvastatin using ICAM-1 antibody-conjugated nanostructured lipid carriers for acute lung injury therapy.
Targeting delivery of simvastatin using ICAM-1 antibody-conjugated nanostructured lipid carriers for acute lung injury therapy.
复制标题
使用 ICAM-1 抗体缀合的纳米结构脂质载体靶向递送辛伐他汀用于急性肺损伤治疗
DOI：
10.1080/10717544.2016.1259369
复制
发表时间：
2017-11
期刊：
影响因子：
6
通讯作者：
Du YZ
中科院分区：
文献类型：
--
作者：
Li SJ;Wang XJ;Hu JB;Kang XQ;Chen L;Xu XL;Ying XY;Jiang SP;Du YZ
急性肺损伤（ALI）是一种目前尚无有效治疗手段的危重病。最近的研究表明他汀类药物对ALI的潜在疗效，而大剂量他汀类药物被认为对减轻体内炎症具有重要意义。因此，肺靶向给药系统（DDS）提供辛伐他汀（SV）的ALI治疗，试图改善与减少剂量的疾病，并尽量减少潜在的不良反应。初步制备了不同粒径的SV纳米结构脂质载体。随着粒径从143.7 nm增加到337.8 nm，SV/NLC的药物包封率从66.70%增加到91.04%。尽管较大的SV/NLC在体外被人血管内皮细胞系EAhy 926在初始阶段表现出较慢的细胞摄取，但体内分布显示较大的SV/NLC在肺中的蓄积较高。因此，将最大尺寸的SV/NLC（337.8 nm）与细胞间粘附分子1（ICAM-1）抗体（抗ICAM/SV/NLC）偶联，用于肺靶向研究。抗ICAM/SV/NLC在脂多糖诱导的ALI小鼠中具有理想的肺靶向性。体内静脉注射抗ICAM/SV/NLC后48 h比游离SV或非靶向SV/NLC更有效地减少TNF-α、IL-6和炎性细胞浸润。H&E染色进一步显示抗ICAM/SV/NLC的显著组织学改善。因此，ICAM-1抗体偶联的NLC可能是一种潜在的肺靶向DDS，有助于他汀类药物治疗ALI。
Abstract Acute lung injury (ALI) is a critical illness without effective therapeutic modalities currently. Recent studies indicated potential efficacy of statins for ALI, while high-dose statins was suggested to be significant for attenuating inflammation in vivo. Therefore, a lung-targeted drug delivery system (DDS) delivering simvastatin (SV) for ALI therapy was developed, attempting to improve the disease with a decreased dose and minimize potential adverse effects. SV-loaded nanostructured lipid carriers (SV/NLCs) with different size were prepared primarily. With particle size increasing from 143.7 nm to 337.8 nm, SV/NLCs showed increasing drug-encapsulated efficiency from 66.70% to 91.04%. Although larger SV/NLCs exhibited slower in vitro cellular uptake by human vascular endothelial cell line EAhy926 at initial stage, while in vivo distribution demonstrated higher pulmonary accumulation of the larger ones. Thus, the largest size SV/NLCs (337.8 nm) were conjugated with intercellular adhesion molecule 1 (ICAM-1) antibody (anti-ICAM/SV/NLCs) for lung-targeted study. The anti-ICAM/SV/NLCs exhibited ideal lung-targeted characteristic in lipopolysaccharide-induced ALI mice. In vivo i.v. administration of anti-ICAM/SV/NLCs attenuated TNF-α, IL-6 and inflammatory cells infiltration more effectively than free SV or non-targeted SV/NLCs after 48-h administration. Significant histological improvements by anti-ICAM/SV/NLCs were further revealed by H&E stain. Therefore, ICAM-1 antibody-conjugated NLCs may represent a potential lung-targeted DDS contributing to ALI therapy by statins.
登录
查看更多内容
影响因子：
17.1
作者：
Howard, Melissa;Zern, Blaine J.;Anselmo, Aaron C.;Shuvaev, Vladimir V.;Mitragotri, Samir;Muzykantov, Vladimir
通讯作者：
Muzykantov, Vladimir
DOI：
10.1186/cc9209
发表时间：
2010
期刊：
Critical care (London, England)
影响因子：
--
作者：
Müller HC;Hellwig K;Rosseau S;Tschernig T;Schmiedl A;Gutbier B;Schmeck B;Hippenstiel S;Peters H;Morawietz L;Suttorp N;Witzenrath M
通讯作者：
Witzenrath M
影响因子：
9.8
作者：
Bouis, Diane;Hospers, Geke A. P.;Mulder, Nanno H.
通讯作者：
Mulder, Nanno H.
DOI：
10.1016/j.jconrel.2010.10.025
发表时间：
2011-02-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Calderon AJ;Bhowmick T;Leferovich J;Burman B;Pichette B;Muzykantov V;Eckmann DM;Muro S
通讯作者：
Muro S
影响因子：
5.8
作者：
Cornier, Marc-Andre;Eckel, Robert H.
通讯作者：
Eckel, Robert H.