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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

Drug delivery - 25(2018), 1 vom: 04. Nov., Seite 1634-1641

Sprache:

Englisch

Beteiligte Personen:

Chu, Liuxiang [VerfasserIn]
Wang, Aiping [VerfasserIn]
Ni, Ling [VerfasserIn]
Yan, Xiuju [VerfasserIn]
Song, Yina [VerfasserIn]
Zhao, Mingyu [VerfasserIn]
Sun, Kaoxiang [VerfasserIn]
Mu, Hongjie [VerfasserIn]
Liu, Sha [VerfasserIn]
Wu, Zimei [VerfasserIn]
Zhang, Chunyan [VerfasserIn]

Links:

Volltext

Themen:

34346-01-5
Antibodies, Monoclonal
Antineoplastic Agents
Drug Carriers
EC 2.7.10.1
EPHA3 antibody
EPHA3 protein, human
Glioblastoma
Journal Article
Nanoparticles
Nose-to-brain delivery
Polyglactin 910
Receptor, EphA3
Receptor Protein-Tyrosine Kinases
Temozolomide
Temozolomide butyl ester
YF1K15M17Y

Anmerkungen:

Date Completed 14.08.2019

Date Revised 09.12.2020

published: Print

Citation Status MEDLINE

doi:

10.1080/10717544.2018.1494226

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM288144368