In vitro and in vivo evaluation of functionalized chitosan-Pluronic micelles loaded with myricetin on glioblastoma cancer

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• 作者：Gang Wang ; PhD^a ; ^b ; ^{wangan139@163.com" class="auth_mail" title="E-mail the corresponding author} ; Jun-Jie Wang ; BS^a ; Xiang-Jun Tang ; MS^b ; Li Du ; MS^a ; Fei Li ; MS^a
• 关键词：ATCC ; American Type Culture Collection ; BBB ; blood&ndash ; brain barrier ; CMC ; critical micelle concentration ; CMC-Na ; sodium carboxymethyl cellulose ; DAB ; diaminobenzidine ; DDS ; drug delivery system ; DL ; drug loading ; EE ; encapsulation efficiency ; GBM ; glioblastoma multiforme ; IACUC ; Institutional Animal Care and Use Committee ; ID ; intragastrically administered dose ; MWCO ; molecular weight cutoff ; MYR ; myricetin ; MYR-MCs ; myricetin-loaded micelles ; PDI ; polydispersity index ; PMA ; phorbol 12-myris
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：12
• 期：5
• 页码：1263-1278
• 全文大小：2677 K

文摘

This study aimed to develop a novel polymeric carrier based on chitosan-functionalized Pluronic P123/F68 micelles loaded with myricetin (MYR) to improve the therapeutic index of chemotherapy for glioblastoma cancer. Following characterization and assessment of the cellular uptake and antitumor effects of MYR-loaded micelles (MYR-MCs) in vitro, the acute toxicity, blood–brain barrier (BBB) translocation, brain uptake and biodistribution in vivo were assessed. The results demonstrated that MYR-MCs exhibited improved cellular uptake and antitumor activity compared to free MYR in vitro, with a significantly enhanced anticancer effect in vivo following efficient transport across the BBB. However, MYR-MCs did not affect the brain endothelial, barrier function, the liver, heart or kidneys. Furthermore, MYR-MCs altered the expression of apoptotic proteins, such as Bcl-2, BAD and BAX, in mice. In conclusion, MYR-MCs may be considered an effective and promising drug delivery system for glioblastoma treatment.