Back to Search
Start Over
A facile approach for crosslinker free nano self assembly of protein for anti-tumor drug delivery: factors' optimization, characterization and in vitro evaluation.
- Source :
-
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2014 Oct 15; Vol. 63, pp. 53-62. Date of Electronic Publication: 2014 Jul 06. - Publication Year :
- 2014
-
Abstract
- We report crosslinker free self assembly of bovine serum albumin (BSA) and a hydrophobic payload paclitaxel (PTX), into nanoparticles by harnessing the temperature driven unfolding of protein. To systematically study the effects of various factors responsible for the key attributes of the nanoparticles, a Resolution IV design was used. 20 formulations were made with pH, temperature, time of heating before and after addition of drug, stirring rate, protein concentration, and protein to drug ratio selected as independent variables. Particle size, encapsulation efficiency, yield and zeta potential were the response variables. Perturbation and Pareto charts were used to single out the important factors, while, mathematical equations and 3D surface charts have been used to describe the relationship between dependent and independent variables. Nanoparticles with size of 188-482 nm were observed with a highly negative zeta potential of -39.5 to -21.9. Nanoparticles obtained had decent encapsulation efficiency (72.5-87.9%) with effective yield (80.0-93.8%). Validation of the mathematical models with 4 runs indicated the good prognostic ability of Resolution IV design. Spectroscopic studies suggested the non-covalent complexation between BSA and PTX as the possible mechanism of self assembly due to irreversible conformational changes in protein. Transmission Electron Microscopy (TEM) revealed spherical nanoparticles with a porous network of PTX-BSA. X-ray Diffraction (XRD) showed amorphous nature of nanoparticles. PTX release from the nanoparticles was found to be controlled release and followed Peppas-Sahlin model. In vitro cytotoxicity of PTX-BSA nanoparticles was comparable to that of Taxol after 48 h treatment. These findings suggest heat driven BSA self assembly as a viable approach to formulate cytotoxic drug carrying nanoparticles which could be efficiently used in anti-cancer therapy.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents chemistry
Cattle
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Particle Size
Structure-Activity Relationship
Surface Properties
Antineoplastic Agents pharmacology
Cross-Linking Reagents chemistry
Drug Carriers chemistry
Nanoparticles chemistry
Serum Albumin, Bovine chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0720
- Volume :
- 63
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 25004412
- Full Text :
- https://doi.org/10.1016/j.ejps.2014.06.022