Delivery of paclitaxel across cellular barriers using a dendrimer-based nanocarrier.
Int J Pharm
; 441(1-2): 701-11, 2013 Jan 30.
Article
de En
| MEDLINE
| ID: mdl-23089576
ABSTRACT
The aim of this study was to investigate the ability of a third-generation (G3) polyamidoamine (PAMAM) dendrimer-based carrier to enhance the permeability of paclitaxel (pac) and to overcome cellular barriers. G3 dendrimers were surface modified with lauryl chains (L) and conjugated with paclitaxel (pac) via a glutaric anhydride (glu) linker, followed by labeling with FITC. Biological evaluation of the dendrimer and conjugates was conducted using the human colon adenocarcinoma cell line (Caco-2) and primary cultured porcine brain endothelial cells (PBECs). LDH assay was used to evaluate the cytotoxicity of the dendrimer and conjugates. Cytotoxicity studies showed that the conjugation of lauryl chains and paclitaxel on G3 dendrimer significantly (p<0.05) increased the cytotoxicity against both cell types. Permeability studies of dendrimer-drug conjugates demonstrated an increase in the apparent permeability coefficient (P(app)) in both apical to basolateral AâB and basolateral to apical BâA directions across both cell monolayers compared to unmodified G3 and free drug. The BâA P(app) of paclitaxel was significantly (p<0.05) higher than the AâB P(app), indicating active function of P-gp efflux transporter system in both cell models. L6-G3-glu-pac conjugate had approximately 12-fold greater permeability across both cell monolayers than that of paclitaxel alone.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Systèmes de délivrance de médicaments
/
Paclitaxel
/
Nanoparticules
/
Antinéoplasiques d'origine végétale
Aspects:
Implementation_research
Limites:
Animals
/
Humans
Langue:
En
Journal:
Int J Pharm
Année:
2013
Type de document:
Article
Pays d'affiliation:
Royaume-Uni