Improved Stability and Enhanced Oral Bioavailability of Atorvastatin Loaded Stearic Acid Modified Gelatin Nanoparticles
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The present study evaluates the effects of stearic acid conjugation with gelatin and, its pharmaceutical potential to formulate novel atorvastatin (AT) loaded nanoparticles.
AT loaded stearic acid modified gelatin nanoparticles (AT-MG NPs) were prepared via two-step desolvation method with extensive optimization of different process variables. Further, the developed nanoparticles where evaluated against in vitro Caco-2 cell model and in vivo bioavailability.
Extensive optimization of nanoformulation resulted into the formation of AT-MG NPs with particle size 247.7 ± 10.9 nm, PDI 0.219 ± 0.07, and entrapment efficiency 58.7 ± 5.3%. Freeze dried nanoparticles were found to have spherical shape as determined by SEM and demonstrated excellent stability in simulated gastrointestinal conditions and during storage. Developed nanoparticles exhibited sustained release up to 24 h and remarkably higher Caco-2 cell uptake. Mechanistic studies further revealed the clathrin and caveolae mediated endocytosis as principle mechanism. In line with Caco-2 cell uptake observations, AT-MG NPs showed ∼4.84-fold increase in the AUC0-∞ values of AT in comparison with free AT following oral administration.
Overall, the stearic acid conjugated gelatin NPs demonstrates a promising potential in improving the drug payload of BCS class II drugs and enhancing oral bioavailability.
Key wordsatorvastatin Caco-2 gelatin nanoparticles oral delivery stearic acid
Area Under the Curve
Confocal Laser-Scanning Microscope
Maximum Concentration Observed
Differential Interference Contrast
Dulbecco’s modified Eagle’s culture medium
Nitric Oxide Synthase
Fetal Bovine Serum
High Density Lipoprotein
3-hydroxy-3-methylglutaryl coenzyme A
Low Density Lipoprotein
Modified Gelatin Nanoparticles
Molecular Weight Cut-Off
Poly Acrylic Acid
Scanning Electron Microscopy
Simulated Gastrointestinal Fluids
Simulated Intestinal Fluid
Sodium Lauryl Sulfate
Acknowledgments and Disclosures
The authors report no financial interest that might pose a potential, perceived, or real conflict of interest. The authors are thankful to the Director, NIPER for providing the necessary infrastructure and facilities. Varun Kushwah and Ashish Kumar Agrawal are grateful to Council of Scientific and Industrial Research (CSIR), GOI, New Delhi, for providing research fellowships.
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