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Tailor-made core-shell nanospheres for antisense oligonucleotide delivery: IV. Adsorption/release behaviour
L Tondelli1, E Canto, A Pistagna
1CNR I Co CEA, Bologna, Italy. tondelli@area.bo.cnr.it
Journal of Biomaterials Science. Polymer Edition
|April 2, 2002
Summary
Oligodeoxynucleotides (ODNs) adsorb onto charged nanospheres via ion pairing, preventing degradation. Nanoparticle-bound ODNs show minimal release in media but gradual release in serum, with no observed cytotoxicity.
Area of Science:
- Materials Science
- Nanotechnology
- Biotechnology
Background:
- Oligodeoxynucleotides (ODNs) are crucial for antisense therapies but susceptible to serum degradation.
- Developing effective delivery systems for ODNs is essential to protect them from degradation and ensure therapeutic efficacy.
- Core-shell polymethylmethacrylate nanospheres offer a potential platform for ODN delivery due to their tunable surface properties.
Purpose of the Study:
- To investigate the adsorption and release behavior of oligodeoxynucleotides (ODNs) on functionalized core-shell nanospheres.
- To elucidate the interaction mechanism between ODNs and nanosphere surface charges.
- To assess the stability and cytotoxicity of ODN-loaded nanospheres.
Main Methods:
- Synthesis of double functional core-shell polymethylmethacrylate nanospheres with quaternary ammonium groups.
- Adsorption studies of ODNs onto nanospheres at varying concentrations and surface charge densities.
- Investigation of ODN release kinetics in culture medium and serum.
- Cytotoxicity assays using PBMC and CEM cells.
Main Results:
- ODN adsorption is driven by ion pair formation between negatively charged ODN phosphates and positively charged nanosphere surfaces.
- Adsorption capacity is dependent on ODN concentration and nanosphere surface charge density.
- An adsorption-induced swelling mechanism enhances ODN binding site accessibility.
- ODNs adsorbed on nanospheres are protected from serum degradation, with negligible release in culture medium but gradual release in serum.
- Nanoparticles showed no significant cytotoxicity at therapeutic ODN concentrations.
Conclusions:
- Functionalized core-shell nanospheres effectively adsorb and protect ODNs from degradation.
- The nanosphere surface charge and ODN concentration are key factors in adsorption efficiency.
- The developed nanocarrier system demonstrates potential for safe and effective ODN delivery, with tunable release characteristics.