Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting

被引：98

作者：

Chu, Liuxiang ^{[1
]}

Wang, Aiping ^{[1
,2
]}

Ni, Ling ^{[2
]}

Yan, Xiuju ^{[1
]}

Song, Yina ^{[1
]}

Zhao, Mingyu ^{[1
]}

Sun, Kaoxiang ^{[1
,2
]}

Mu, Hongjie ^{[1
]}

Liu, Sha ^{[1
]}

Wu, Zimei ^{[1
]}

Zhang, Chunyan ^{[1
]}

机构：

[1] Yantai Univ, Univ Shandong, Collaborat Innovat Ctr Adv Drug Delivery Syst & B, Sch Pharm, Yantai 264005, Peoples R China

[2] Shandong Luye Pharmaceut Co Ltd, State Key Lab Long Acting & Targeting Drug Delive, Yantai, Peoples R China

来源：

DRUG DELIVERY | 2018年 / 25卷 / 01期

关键词：

Glioblastoma; EPHA3; antibody; temozolomide butyl ester; nose-to-brain delivery; nanoparticles; NANOSTRUCTURED LIPID CARRIERS; DRUG-DELIVERY; INTRANASAL DELIVERY; CHITOSAN; EPHA3; GLIOMA; NASAL; MULTIFORME; PROGRESS; INSULIN;

D O I：

10.1080/10717544.2018.1494226

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Glioblastoma is the most common malignant brain tumor. Efficient delivery of drugs targeting glioblastomas remains a challenge. Ephrin type-A receptor 3 (EPHA3) tyrosine kinase antibody-modified polylactide-co-glycolide (PLGA) nanoparticles (NPs) were developed to target glioblastoma via nose-to-brain delivery. Anti-EPHA3-modified, TBE-loaded NPs were prepared using an emulsion-solvent evaporation method, showed a sustained in vitro release profile up to 48 h and a mean particle size of 145.9 +/- 8.7 nm. The cellular uptake of anti-EPHA3-modified NPs by C6 cells was significantly enhanced compared to that of nontargeting NPs (p < .01). In vivo imaging and distribution studies on the glioma-bearing rats showed that anti-EPHA3-modified NPs exhibited high fluorescence intensity in the brain and effectively accumulated to glioma tissues, indicating the targeting effect of anti-EPHA3. Glioma-bearing rats treated with anti-EPHA3-modified NPs resulted in significantly higher tumor cell apoptosis (p < .01) than that observed with other formulations and prolonged the median survival time of glioma-bearing rats to 26 days, which was 1.37-fold longer than that of PLGA NPs. The above results indicated that anti-EPHA3-modified NPs may potentially serve as a nose-to-brain drug carrier for the treatment of glioblastoma.

引用

页码：1634 / 1641

页数：8

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