Deepanshu Shilpi1, Varun Kushwah1, Ashish Kumar Agrawal1,2, Sanyog Jain3. 1. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research,, SAS Nagar, Punjab, 160062, India. 2. James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky, 40202, USA. 3. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research,, SAS Nagar, Punjab, 160062, India. sanyogjain@niper.ac.in.
Abstract
PURPOSE: The present study evaluates the effects of stearic acid conjugation with gelatin and, its pharmaceutical potential to formulate novel atorvastatin (AT) loaded nanoparticles. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: The present study evaluates the effects of stearic acid conjugation with gelatin and, its pharmaceutical potential to formulate novel atorvastatin (AT) loaded nanoparticles. METHOD: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Dimitrios I Zeugolis; Shih T Khew; Elijah S Y Yew; Andrew K Ekaputra; Yen W Tong; Lin-Yue L Yung; Dietmar W Hutmacher; Colin Sheppard; Michael Raghunath Journal: Biomaterials Date: 2008-03-03 Impact factor: 12.479
Authors: Sawsan Youssef; Olaf Stüve; Juan C Patarroyo; Pedro J Ruiz; Jennifer L Radosevich; Eun Mi Hur; Manuel Bravo; Dennis J Mitchell; Raymond A Sobel; Lawrence Steinman; Scott S Zamvil Journal: Nature Date: 2002-11-07 Impact factor: 49.962