Application of quality-by-design approach to optimize diallyl disulfide-loaded solid lipid nanoparticles.
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.
a Department of Pharmaceutics , JSS College of Pharmacy, JSS University , Udhagamandalam , Tamil Nadu , India.
Siddhartha Venkata
SV
Talluri
a Department of Pharmaceutics , JSS College of Pharmacy, JSS University , Udhagamandalam , Tamil Nadu , India.
Gowthamarajan
G
Kuppusamy
a Department of Pharmaceutics , JSS College of Pharmacy, JSS University , Udhagamandalam , Tamil Nadu , India.
Veera Venkata Satyanarayana Reddy
VV
Karri
b Department of Pharmaceutical Analysis , JSS College of Pharmacy, JSS University , Udhagamandalam , Tamil Nadu , India.
Karthik
K
Yamjala
c Department of Pharmaceutical Biotechnology , JSS College of Pharmacy, JSS University , Udhagamandalam , Tamil Nadu , India.
Ashish
A
Wadhwani
d Department of Biochemistry , JSS Medical College, JSS University , Mysore , Karnataka , India.
SubbaRao V
SV
Madhunapantula
e Department of Pharmacology , JSS College of Pharmacy, JSS University , Udhagamandalam , Tamil Nadu , India.
Saikiran S S
SS
Pindiprolu
D000498:Allyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D005163:Factor Analysis, Statistical; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D019308:Palmitic Acid / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry* / Q000378:metabolism
D000498:Allyl Compounds; D000970:Antineoplastic Agents; D004220:Disulfides; D004337:Drug Carriers; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D013501:Surface-Active Agents; D019308:Palmitic Acid; C028009:diallyl disulfide
Box–Behnken design; breast cancer; design of experiment; diallyl disulfide; solid lipid nanoparticles