Paclitaxel-loaded Nanolipidic Carriers with Improved Oral Bioavailability and Anticancer Activity against Human Liver Carcinoma.
AAPS PharmSciTech
; 20(2): 87, 2019 Jan 23.
Article
em En
| MEDLINE
| ID: mdl-30675689
ABSTRACT
The poorly water-soluble chemotherapeutic agents, paclitaxel (PTX), exhibit serious clinical side effects upon oral administration due to poor aqueous solubility and a high degree of toxic effects due to non-specific distribution to healthy tissues. In our efforts, we formulated biocompatible dietary lipid-based nanostructured lipidic carriers (NLCs) to enhance the oral bioavailability of PTX for treatment of the liver cancer. A three-factor, three-level Box-Behnken design was employed for formulation and optimization of PTX-loaded NLC formulations. PTX-loaded NLC formulation prepared by melt-emulsification in which glyceryl monostearate (GMS) was used as solid lipid and soybean oil as liquid lipid, while poloxamer 188 and Tween 80 (11) incorporated as a surfactant. In vitro drug release investigation was executed by dialysis bag approach, which indicated initial burst effect with > 60% drug release within a 4-h time period. Moreover, PTX-NLCs indicated high entrapment (86.48%) and drug loading efficiency (16.54%). In vitro cytotoxicity study of PTX-NLCs performed on HepG2 cell line by MTT assay indicated that PTX-NLCs exhibited comparatively higher cytotoxicity than commercial formulation (Intaxel®). IC50 values of PTX-NLCs and Intaxel® after 24-h exposure were found to be 4.19 µM and 11.2 µM. In vivo pharmacokinetic study in Wistar rats also indicated nearly 6.8-fold improvement in AUC and Cmax of the drug from the PTX-NLCs over the PTX suspension. In a nutshell, the observed results construed significant enhancement in the biopharmaceutical attributes of PTX-NLCs as a potential therapy for the management of human liver carcinoma.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Paclitaxel
/
Lipídeos
/
Neoplasias Hepáticas
/
Antineoplásicos Fitogênicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
AAPS PharmSciTech
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Índia