In vivo distribution and antitumor activity of doxorubicin-loaded N-isopropylacrylamide-co-methacrylic acid coated mesoporous silica nanoparticles and safety evaluation

被引：52
作者：
Chen, Yanzuo [1 ]
Yang, Wuli [2 ]
Chang, Baisong [2 ]
Hu, Hangting [1 ]
Fang, Xiaoling [1 ]
Sha, Xianyi [1 ]
机构：
[1] Fudan Univ, Sch Pharm, Dept Pharmaceut, Key Lab Smart Drug Delivery,Minist Educ, Shanghai 201203, Peoples R China
[2] Dept Macromol Sci, State Key Lab Mol Engn Polymers, Shanghai, Peoples R China
来源：
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2013年 / 85卷 / 03期
基金：
中国国家自然科学基金;
关键词：
N-isopropylacrylamide-co-methacrylic acid; Mesoporous silica nanoparticles; Doxorubicin; Antitumor activity; Safety evaluation; Nanoparticles; DRUG-DELIVERY; INDUCED CARDIOTOXICITY; BIODISTRIBUTION; PHARMACOKINETICS; ADRIAMYCIN; LIPOSOMES; MICE; TOXICITY; SYSTEM; AGENTS;
D O I：
10.1016/j.ejpb.2013.06.015
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
The objective of this study was to develop and evaluate the antitumor activity and the safety of a delivery system containing mesoporous silica nanoparticles (MSN) coated with pH-responsive poly (N-isopropyl-acrylamide-co-methacrylic acid; P NIPAM-co-MAA) for doxorubicin (DOX) delivery (P-MSN-DOX) in vitro and in vivo. We reported that P-MSN-DOX nanoparticles (190 +/- 30 nm) offered a DOX-loading coefficient of more than 20%. DOX release from the P-MSN-DOX formulation was pH-dependent with enhanced antitumor effects in vitro compared with traditional MSN-DOX, which was weakly cytotoxic due to negligible drug release at tested pHs. P-MSN-DOX circulated longer, with less cardiac and renal accumulation as shown by pharmacokinetics and biodistribution studies in vivo. Also, the P-MSN-DOX delivery system had greater antitumor activity in mice bearing a murine sarcoma S-180 cell line. This finding was correlated with both in vitro and in vivo. Subacute toxicity tests revealed a low P-MSN-DOX toxicity in vivo, as well. Thus, P-MSN-DOX appears to be an efficacious and safe cancer treatment strategy. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码：406 / 412
页数：7
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