Hybrid Nanoparticle Design Based on Cationized Gelatin and the Polyanions Dextran Sulfate and Chondroitin Sulfate for Ocular Gene Therapy

• Published in: Macromolecular bioscience 2011-07, Vol.11 (7), p.905-913
• Main Authors: Zorzi, Giovanni Konat, Párraga, Jenny Evelin, Seijo, Begoña, Sánchez, Alejandro
• Format: Article
• Language: English
• Subjects: Anions; Applied sciences; Biological and medical sciences; Cations; Cations - chemistry; Cells, Cultured; Chondroitin Sulfates - chemistry; Cornea - chemistry; Cornea - metabolism; Deoxyribonuclease I; Dextran Sulfate - chemistry; DNA - metabolism; drug delivery systems; Exact sciences and technology; Gelatin - chemistry; Gelatins; gelation; Gene therapy; General pharmacology; Genetic Therapy; Humans; Medical sciences; Microscopy, Electron, Transmission; Nanocomposites; Nanomaterials; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Nanostructure; nanotechnology; Natural polymers; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Plasmids - genetics; Polymers - chemistry; Starch and polysaccharides; Sulfates; Transfection
• ISSN: 1616-5187; 1616-5195; 1616-5195
• DOI: 10.1002/mabi.201100005

We describe the development of hybrid nanoparticles composed of cationized gelatin and the polyanions CS and DS for gene therapy in the ocular surface. The physicochemical properties of the nanoparticles that impact their bioperformance, such as average size and zeta potential, can be conveniently modulated by changing the ratio of polymers and the crosslinker. These systems associate plasmid DNA and are able to protect it from DNase I degradation. We corroborate that the introduction of CS or DS in the formulation decreases the in vitro toxicity of the nanoparticles to human corneal cells without compromising the transfection efficiency. These nanoparticles are potential candidates for the development of safer and more effective nanomedicines for ocular therapy. New hybrid nanoparticles composed of cationized gelatin and natural polyanions are developed and characterized. The incorporation of chondroitin sulfate or dextran sulfate in cationized gelatin nanoparticles decreases their toxicity while preserving their transfection efficiency in human corneal cells. These nanoparticles are potential candidates for the development of safer and more effective nanomedicines for ocular therapy.