Folate-Targeted Cholesterol-Grafted Lipo-Polymeric Nanoparticles for Chemotherapeutic Agent Delivery.
AAPS PharmSciTech
; 21(7): 280, 2020 Oct 09.
Article
em En
| MEDLINE
| ID: mdl-33037506
ABSTRACT
Docetaxel (DTX), an FDA approved chemotherapeutic agent, is used as a first-line treatment for triple-negative breast cancer (TNBC). Its poor aqueous solubility, rapid metabolism, short half-life, and effective targeting to the cancer cells limits its optimal therapeutic use. Herein, we report folate targeted amphiphilic lipopolymer grafted with cholesterol conjugated carbonate and DL-lactide prepared by microwave assisted ring opening polymerization, for the efficient actively targeted delivery of DTX. The DTX-loaded folate-targeted lipopolymeric nanoparticles (F-DTX-LPNs) prepared by the emulsion solvent evaporation method exhibited a smaller size of â¼115.17 nm with a PDI of 0.205 and encapsulation efficiency of >80%. Further, these lipopolymeric nanoparticles (F-DTX-LPNs) showed a good on-bench stability and sustained DTX release for 7 days. Cell-based assays in MDA-MB-231 cells revealed a significant enhancement in the intracellular uptake of folate-targeted lipopolymeric nanoparticles compared to non-targeted nanoparticles. Further, methyl beta-cyclodextrin (Mß-CD) completely inhibited the uptake of these nanoparticles in the cells, indicating a lipid raft-mediated uptake mechanism. The developed F-DTX-LPNs showed improved cytotoxicity, apoptosis, and significant fold-change in expression levels of Bcl-2, BAX and Ki-67 as compared to non-targeted DTX-LPNs and free DTX. Further, F-DTX-LPNs showed an improved in vivo pharmacokinetic profile in Sprague Dawley rats as compared to the free DTX. The bio-imaging of ex vivo tissues demonstrated that the DiR loaded folate targeted LPNs exhibited intense signals after 24 h because of slow release of DiR dye from the nanoparticles.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Portadores de Fármacos
/
Colesterol
/
Ácido Fólico
/
Docetaxel
/
Antineoplásicos Fitogênicos
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article