Novel Aqueous solvent based method for protein based nanoparticles

Order of Publishing in Issue: 
Volume :2
Issue :4
October, 2008
Page No: 
575 -584
M. M. Ibrahim1,2, O. A. Sammour3, M. A. Hammad2, N. A. Megrab2, X. Li1 and B. Jasti1*
1Thomas J. Long school of Pharmacy, University of the Pacific, Stockton, CA; 2Dept. of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt; 3Dept. of Drug Technology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

The objective of the present study is to develop a novel method for the preparation ofpoly(D,L-lactide-co-glycolide)(PLGA) nanoparticles for protein/peptide delivery, and compare this method with traditional solvent evaporation methods for nanoparticle particlesize and entrapment efficiency. The nanoparticles were prepared by three different methods namely:w/o/w emulsification-solvent evaporation method (ESE), nanoprecipitation method, andnovel aqueous mixed micelle (MM) method. The prepared nanoparticles were evaluated as drugcarrier systems using bovine serum albumin (BSA) as a model peptide. The physicochemicalcharacteristics of the nanoparticles; morphology, particle size, zeta potential, and the effect ofdifferent parameters (method of preparation, time of stirring, drug concentration, and polymerconcentration) on particle size and protein encapsulation efficiency percent (EE%) werestudied. Severe aggregation of nanoparticles was noticed after freeze drying, especially for MMmethod. To reduce or completely prevent nanoparticle aggregation during freeze drying,three sugar cryoprotectants (glucose, trehalose,and mannitol) were evaluated. Results showedthat all the preparation methods yielded greater than 90% EE of BSA into nanoparticles.Increasing the time of stirring during preparation decreased the particle size and was of a littleeffect on EE% in case of ESE and nanoprecipitation methods. On the other hand,the time of stirring has no effect on the particlesize and EE% in case of MM method. Increasing the drug concentration and PLGA concentration was found to increase both particle size and EE%.Both glucose and trehalose protected nanoparticles from aggregation during freezedrying while mannitol had increased their aggregation. In conclusion, this study suggestedthe potential of preparing PLGA nanoparticles using aqueous solvent that can be used for loadingpeptide drugs.

Emulsification, Nanoprecipitation, Mixed micelle, Nanoparticles, PLGA
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