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Physicochemical characterization of protamine-phosphorothioate nanoparticles
D Lochmann1, V Vogel, J Weyermann
1Institute for Pharmaceutical Technology, Johann Wolfgang Goethe-University, Marie-Curie-Strasse 9, 60439 Frankfurt am Main, Germany.
Journal of Microencapsulation
|March 15, 2005
Summary
Protamine-oligonucleotide nanoparticles effectively carry antisense phosphorothioate oligonucleotides (PTO). Optimized preparation yields stable nanoparticles, with polyethylenglycol enhancing their stability in cell media.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery
Background:
- Antisense phosphorothioate oligonucleotides (PTO) are promising therapeutic agents.
- Protamine-oligonucleotide nanoparticles serve as effective colloidal drug carriers for PTO.
- Optimization of nanoparticle preparation and characterization is crucial for drug delivery applications.
Purpose of the Study:
- To improve the preparation of protamine-oligonucleotide nanoparticles.
- To characterize the physicochemical properties of these nanoparticles.
- To investigate factors influencing particle formation, size, shape, and surface charge.
Main Methods:
- Dynamic light scattering (DLS) for assembly kinetics and particle size.
- Analytical ultracentrifuge (AUC) for sedimentation velocity analysis and stability.
- Scanning electron microscopy (SEM) and atomic force microscopy (AFM) for morphological verification.
Main Results:
- Nanoparticles (90-200nm) were formed using protamine free base (PFB) and PTO in water.
- High PTO incorporation (>90%) achieved with PTO/PFB ratio >= 1:2 (w/w).
- Zetapotential ranged from -19 to +32 mV; particles moderately stable in water, unstable in salt solutions.
- Polyethylenglycol 20000 (PEG) stabilized colloidal solutions in water and cell medium.
Conclusions:
- Optimized protamine-oligonucleotide nanoparticle preparation yields efficient drug carriers.
- Physicochemical properties, including size and charge, are tunable via component ratios.
- PEGylation enhances nanoparticle stability, crucial for in-cell applications.