Compositions and methods for controlled delivery of inhibitory ribonucleic acids

摘要

Polymeric nanoparticles encapsulating inhibitory ribonucleic acids (RNAs) and methods of their manufacture and use are provided. Advantageous properties of the nanoparticles include: 1) high encapsulation efficiency of inhibitory RNAs into the nanoparticles, 2) small size of the nanoparticles that increases cell internalization, and 3) sustained release of encapsulated inhibitory RNAs by the nanoparticles that allows for administration of an effective amount of inhibitory RNAs to cells or tissues over extended periods of time. Encapsulation efficiency of inhibitory RNAs into the nanoparticles is greatly increased by complexing the inhibitory RNAs to polycations prior to encapsulation. Methods of using the polymeric nanoparticles for treating or inhibiting diseases or disorders are provided.

主权项

1. A composition for intracellular delivery of inhibitory polynucleotides consisting essentially of
polymeric nanoparticles, and inhibitory polynucleotides complexed to a polyamine polycation in a molar ratio of the polycation nitrogen (“N”) to the polynucleotide phosphate (“P”) of between approximately 8:1 and 15:1, wherein the nanoparticles are prepared by first forming the polynucleotide-polycation complex in the absence of the polymer of the nanoparticle and subsequently contacting the polynucleotide-polycation complex with the polymer to form nanoparticles encapsulating the polynucleotide-polycation complex, wherein the polynucleotide-polycation complex encapsulated nanoparticles are formed by a double-emulsion technique comprising (i) adding an aqueous solution comprising the polynucleotide-polycation complexes to a polymer solution comprising the polymer dissolved in an organic solvent to form a first emulsion; (ii) adding the first emulsion to a first surfactant solution followed by mixing to form a second emulsion; (iii) adding the second emulsion to a second surfactant solution; and (iv) removing the organic solvent to yield polynucleotide-polycation complex encapsulated nanoparticles.