Integrity and Bioactivity of Insulin Loaded PLGA Nanoparticles Prepared by a Novel Aquesou Method and its Comparison to Emulsion Solvent Evaporation Method

Order of Publishing in Issue: 
1
Volume :5
Issue :2
Regular
April, 2011
Page No: 
1084-1097
Authors: 
Mahmoud M. Ibrahim, [1,2] Omaima A.Sammour,[3] Mohamed Hammad,[2] Nagia A. Megrab [2], Xiaoling Li1 and Bhaskara Jasti [1]*
Address: 
[1] Thomas J. Long School of Pharmacy and Health Sci, University of the Pacific, Stockton, CA, USA
Address: 
[2] Dept. of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
Address: 
[3] Dept. of Drug Technology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
Email-ID: 
bjasti@pacific.edu

Poly lactic-coglycolic acid polymer nanoparticles of insulin were prepared by a novel aqueous based mixed micelle (MM) method and traditional emulsion solvent evaporation method that use organic solvents. The particle size and entrapment efficiency and insulin release from the nanoparticles were determined. The integrity of the entrapped insulin, bioactivity and immunogenicity were investigated using MALDI MS, cell viability assay, and ELISA tests. The pharmacodynamic activity of the entrapped insulin in nanoparticles was compared with its subcutaneous administration in diabetic rats. The nanoparticles released 50% of insulin immediately at pH 7.4, followed by slow release of the remaining entrapped insulin. At pH 1.2, complete release of insulin occurred within 5 minutes. At a pH closer to PI of insulin, the burst release decreased to 8%. The molecular mass, cell viability and Elisa test showed that insulin retained its integrity and activity. The blood glucose levels in rats showed sustained reduction following the administration of insulin loaded nanoparticles suggesting that insulin activity in nanoparticles prepared by MM and ESE methods has remained intact.

Keywords: 
Bioactivity, Immunogenicity, Insulin integrity, Mixed micelle, Nanoparticles
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