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Nose-to-brain delivery of disulfiram nanoemulsion in situ gel formulation for glioblastoma targeting therapy.

Abstract：

:Glioblastoma (GBM) is a difficult-to-treat cancer, likely attributed to the blood brain barrier and drug resistance. Nose-to-brain drug delivery is a direct and non-invasive pathway for brain targeting with low systemic toxicity. Disulfiram (DSF) has shown its effectiveness against GBM, especially with copper ion (Cu). In this work, we designed a DSF loaded ion-sensitive nanoemulsion in situ gel (DSF-INEG) that was delivered intranasally along with Cu to the rat brains for the GBM treatment. The developed DSF-INEG nanomedicine showed a suitable particle size of 63.4 ± 1.1 nm and zeta potential of -23.5 ± 0.2 mV with a favorable gelling ability and prolonged DSF release. The results in vitro indicate DSF-INEG/Cu effectively inhibited the proliferation of both C6 and U87 cells. Besides, the excellent brain-targeting efficacy via nose-to-brain delivery was proved by the highest fluorescence signal of Cy5.5-INEG in the rat brains. Moreover, GFP imaging showed enhanced tumor growth inhibition of the rats by the DSF-INEG/Cu treatment, and their median survival time was 1.6 and 1.2 folds than those of the rats in the control and DSF/Cu treated groups, respectively, with no obvious histopathological damage to normal tissues. Overall, DSF-INEG/Cu could be a promising intranasal nanomedicine for effective GBM treatment.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Qu Y,Li A,Ma L,Iqbal S,Sun X,Ma W,Li C,Zheng D,Xu Z,Zhao Z,Ma D

doi

10.1016/j.ijpharm.2021.120250

subject

Has Abstract

pub_date

2021-01-21 00:00:00

pages

120250

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(21)00054-5

pub_type

杂志文章

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