Pharmaceutical Research

, Volume 34, Issue 7, pp 1505–1516 | Cite as

Improved Stability and Enhanced Oral Bioavailability of Atorvastatin Loaded Stearic Acid Modified Gelatin Nanoparticles

  • Deepanshu Shilpi
  • Varun Kushwah
  • Ashish Kumar Agrawal
  • Sanyog JainEmail author
Research Paper



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 words

atorvastatin Caco-2 gelatin nanoparticles oral delivery stearic acid 



Atorvastatin calcium


Area Under the Curve




Confocal Laser-Scanning Microscope


Maximum Concentration Observed




Differential Interference Contrast


Dulbecco’s modified Eagle’s culture medium


N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride


Nitric Oxide Synthase


Fetal Bovine Serum


Gastrointestinal Tract




High Density Lipoprotein


3-hydroxy-3-methylglutaryl coenzyme A


Low Density Lipoprotein


Modified Gelatin


Modified Gelatin Nanoparticles


Molecular Weight Cut-Off




Native Gelatin


Poly Acrylic Acid


Polydispersity Index


Stearic 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.

Supplementary material

11095_2017_2173_MOESM1_ESM.docx (420 kb)
ESM 1 (DOCX 419 kb)


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Deepanshu Shilpi
    • 1
  • Varun Kushwah
    • 1
  • Ashish Kumar Agrawal
    • 1
    • 2
  • Sanyog Jain
    • 1
    Email author
  1. 1.Centre for Pharmaceutical Nanotechnology, Department of PharmaceuticsNational Institute of Pharmaceutical Education and Research,SAS NagarIndia
  2. 2.James Graham Brown Cancer CenterUniversity of LouisvilleLouisvilleUSA

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