Trastuzumab decorated TPGS-g-chitosan nanoparticles for targeted breast cancer therapy.
Colloids Surf B Biointerfaces
; 173: 366-377, 2019 Jan 01.
Article
in En
| MEDLINE
| ID: mdl-30316083
ABSTRACT
Breast cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) has led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted as well as targeted nanoparticles were in the range of 126-186 nm and 74-78% respectively. In-vitro studies on SK-BR-3 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional formulation i.e., Docel™. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than Docel™. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than Docel™. Further, after i.v administration, non-targeted and targeted nanoparticles achieved 3.48 and 5.94 times prolonged half-life in comparison to Docel™. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles when compared to Docel™. The histopathology studies of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney when compared to Docel™.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vitamin E
/
Breast Neoplasms
/
Glycoconjugates
/
Adenocarcinoma
/
Trastuzumab
/
Docetaxel
/
Antineoplastic Agents
Type of study:
Prognostic_studies
Language:
En
Journal:
Colloids Surf B Biointerfaces
Journal subject:
QUIMICA
Year:
2019
Document type:
Article
Affiliation country: