Faculty Collaboration Database

Dendrimer-stabilized smart-nanoparticle (DSSN) platform for targeted delivery of hydrophobic antitumor therapeutics. Pharm Res 2015 Mar;32(3):910-28

Date

09/11/2014

Pubmed ID

25205461

DOI

10.1007/s11095-014-1506-0

Scopus ID

2-s2.0-84922998546 (requires institutional sign-in at Scopus site)   68 Citations

Abstract

PURPOSE: To formulate dendrimer-stabilized smart-nanoparticle (DSSN; pD-ANP-f) for the targeted delivery of the highly hydrophobic anticancer drug, Paclitaxel (PTXL).

METHOD: The developed nanoformulations were evaluated for particle size, surface-charge, loading efficiency, particle density, in-vitro drug release, SEM/TEM, cytotoxicity assay, fluorescence uptake, HPLC quantitative cell uptake assay, flow cytometry, tubulin polymerization, and stability assessments.

RESULTS: The developed pD-ANP-f nanoformulation (135.17 ± 7.39 nm; -2.05 ± 0.37 mV and 80.11 ± 4.39% entrapment) exhibited a pH-dependent drug release; remained stable in physiological pH, while rapid releasing PTXL under tumorous environment (pH 5.5). The cytotoxicity assay performed in cervical, breast, blood, and liver cancer cell lines showed pD-ANP-f to be strongly suppressing the growth of cancer cells. We investigated the fluorescence based intracellular trafficking and HPLC based cellular uptake of nanoformulated drug and the result indicates higher cellular uptake of pD-ANP-f compared to other formulations. pD-ANP-f prominently induced apoptosis (73.11 ± 3.84%) and higher polymerization of tubulins (59.73 ± 6.22%). DSSN nanoformulation was found to be extremely biocompatible (<1% hemolytic) compared to naked PTXL (19.22 ± 1.01%) as well as PTXL-dendrimer nanocomplex (8.29 ± 0.71%).

CONCLUSION: DSSN strategy is a novel and promising platform for biomedical applications that can be effectively engaged for the delivery of drug/gene/siRNA targeting.

Author List

Tekade RK, Tekade M, Kumar M, Chauhan AS

Author

Abhay Chauhan PhD Associate Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents, Phytogenic
Apoptosis
Cell Proliferation
Chemistry, Pharmaceutical
Dendrimers
Dose-Response Relationship, Drug
Drug Carriers
Drug Stability
Hemolysis
Hep G2 Cells
Humans
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Inhibitory Concentration 50
Jurkat Cells
Kinetics
MCF-7 Cells
Microtubules
Nanoparticles
Nanotechnology
Neoplasms
Paclitaxel
Particle Size
Solubility
Surface Properties
Technology, Pharmaceutical
Tubulin Modulators