Enhanced passive pulmonary targeting and retention of PEGylated rigid microparticles in rats.
Enhanced passive pulmonary targeting and retention of PEGylated rigid microparticles in rats.
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DOI：
10.1016/j.ijpharm.2010.09.020
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发表时间：
2010-12-15
影响因子：
5.8
通讯作者：
Sinko, Patrick J.
中科院分区：
文献类型：
--
作者：
Kutscher, Hilliard L.;Chao, Piyun;Deshmukh, Manjeet;Rajan, Sujata Sundara;Singh, Yashveer;Hu, Peidi;Joseph, Laurie B.;Stein, Stanley;Laskin, Debra L.;Sinko, Patrick J.
关键词：
本研究考察了6 μm聚苯乙烯（PS）微粒（MP）的被动肺靶向效力和滞留，所述PS微粒（MP）共价修饰有不同的表面基团[胺（A-）、羧基（C-）和硫酸根（S-）]或单层（PEG 1-）和双层（PEG 2-）的α，ω-二氨基聚（乙二醇）连接至C-MP。A-MP（-44.0 mV）、C-MP（-54.3 mV）和S-MP（-49.6 mV）在去离子水中的电位是相似的;然而PEG化增加了PEG 1-MP（-18.3 mV）和PEG 2-MP（11.5 mV）的电位。用荧光分光光度法测定静脉注射MPs对雄性Sprague道利大鼠的生物分布和滞留。与未修饰的A-MP相比，PEG 1-MP和PEG 2-MP在注射后48小时在大鼠中表现出增强的肺滞留（分别为给药剂量的59.6%、35.9%和17.0%）。虽然未修饰的MP没有显著改变肺滞留，但MP的PEG化通过修饰表面性质（包括电荷和疏水性，但不包括尺寸）出乎意料地改善了被动肺靶向和滞留。
The current study examines the passive pulmonary targeting efficacy and retention of 6 μm polystyrene (PS) microparticles (MPs) covalently modified with different surface groups [amine (A-), carboxyl (C-) and sulfate (S-)] or single (PEG1-) and double (PEG2-) layers of α,ω-diamino poly(ethylene glycol) attached to C-MPs. The ζ-potential of A-MPs (-44.0 mV), C-MPs (-54.3 mV) and S-MPs (-49.6 mV) in deionized water were similar; however PEGylation increased the ζ-potential for both PEG1-MPs (-18.3 mV) and PEG2-MPs (11.5 mV). The biodistribution and retention of intravenously administered MPs to male Sprague Dawley rats was determined in homogenized tissue by fluorescence spectrophotometry. PEG1-MPs and PEG2-MPs demonstrated enhanced pulmonary retention in rats at 48 h after injection when compared to unmodified A-MPs (59.6%, 35.9% and 17.0% of the administered dose, respectively). While unmodified MPs did not significantly change lung retention, PEGylation of MPs unexpectedly improved passive lung targeting and retention by modifying surface properties including charge and hydrophobicity but not size.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
14
作者：
HARPER, GR;DAVIES, MC;WATERS, JA
通讯作者：
WATERS, JA
影响因子：
10.8
作者：
Norris, DA;Puri, N;Sinko, PJ
通讯作者：
Sinko, PJ
影响因子：
10.8
作者：
Kutscher, Hilliard L.;Chao, Piyun;Deshmukh, Manjeet;Singh, Yashveer;Hu, Peidi;Joseph, Laurie B.;Reimer, David C.;Stein, Stanley;Laskin, Debra L.;Sinko, Patrick J.
通讯作者：
Sinko, Patrick J.
影响因子：
2.3
作者：
Chao P;Deshmukh M;Kutscher HL;Gao D;Rajan SS;Hu P;Laskin DL;Stein S;Sinko PJ
通讯作者：
Sinko PJ