1. Application of quality-by-design approach to optimize diallyl disulfide-loaded solid lipid nanoparticles.
- Author
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Talluri SV, Kuppusamy G, Karri VV, Yamjala K, Wadhwani A, Madhunapantula SV, and Pindiprolu SS
- Subjects
- Allyl Compounds chemistry, Antineoplastic Agents chemistry, Apoptosis drug effects, Biological Transport, Cell Survival drug effects, Disulfides chemistry, Dose-Response Relationship, Drug, Drug Compounding, Drug Liberation, Factor Analysis, Statistical, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Hydrogen-Ion Concentration, Kinetics, MCF-7 Cells, Nanoparticles ultrastructure, Neoplasm Proteins genetics, Neoplasm Proteins metabolism, Palmitic Acid metabolism, Particle Size, Reactive Oxygen Species agonists, Reactive Oxygen Species metabolism, Surface-Active Agents metabolism, Allyl Compounds pharmacology, Antineoplastic Agents pharmacology, Disulfides pharmacology, Drug Carriers, Nanoparticles chemistry, Palmitic Acid chemistry, Surface-Active Agents chemistry
- Abstract
The current work was carried out by the principles of quality-by-design approach to develop an optimized solid lipid nanoparticles (SLNs) formulation of diallyl disulfide (DADS) through systematic statistical study. And its antitumor activity of DADS was also evaluated on breast cancer cell lines. To understand the effect of formulation variables (critical parameters) on the responses (critical quality attributes) of SLN, a 3-factor, 3-level Box-Behnken design, was explored to predict the responses such as particle size (Y1) and % entrapment efficiency (EE) (Y2) when concentration of surfactant (X1), amount of lipid (X2), and volume of solvent (X3) were selected as independent variables. Particle size analysis revealed that all the batches were within the nanometer range. DADS was released from the SLN much more rapidly at pH 4.5 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. The cytotoxicity, reactive oxygen species (ROS), determination revealed that the antitumor activity of DADS is enhanced with SLN compared to DADS-free drug, and apoptosis is the mechanism underlying the cytotoxicity. The present study indicated the remarkable potential of DADS-SLN in enhancing the anticancer effect of DADS in breast cancer cells in vitro.
- Published
- 2017
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