Composite nano-carrier capable of loading nucleic acid drugs efficiently and preparation method of composite nano-carrier

Abstract

The invention relates to a composite nano-carrier capable of loading nucleic acid drugs efficiently and a preparation method of the composite nano-carrier. The composite nano-carrier is composed of a degradable organic material and polyamine with different molecular weights, wherein the mass ratio of the polyamine with different molecular weights to the degradable organic material is (0.005: 100)-(3:7), the composite nano-carrier is spherical, the particle size of the composite nano-carrier ranges from 80 nm to 950 nm, and the nucleic acid drugs are distributed in the composite nano-carrier uniformly. The preparation method of the composite nano-carrier includes steps of firstly, dissolving the nucleic acid drugs into water to obtain internal water phase, dissolving the degradable organic material and the polyamine with different molecular weights into organic solvent to obtain organic phase, taking polyving alcohol aqueous solution as external water phase; secondly, emulsifying the internal water phase into the organic phase under ultrasonic action of a probe so as to form water-in-oil colostrum, emulsifying the water-in-oil colostrum into the external water phase under ultrasonic action of the probe so as to obtain oil-in-water multiple emulsion, stirring the multiple emulsion by magnetic force at room temperature so as to remove the organic solvent in the organic phase by volatilizing, performing centrifugal separation after nano-particles are solidified, washing the nano-particles with double distilled water so as to obtain the composite nano-carrier capable of loading nucleic acid drugs.

Description

technical field [0001] The invention relates to a composite nanocarrier capable of efficiently loading nucleic acid drugs and a preparation method thereof. Background technique [0002] Gene therapy by expressing biologically active substances, inhibiting dysfunctional genes that lead to genetic disorders or uncontrolled cell proliferation is a powerful method for the prevention and treatment of many major diseases such as genetic defect diseases, infections, tumors and cardiovascular diseases. At present, the lack of safe and effective gene carriers is the main bottleneck limiting the wide application of gene therapy in clinic. Although viral vectors, such as adenoviruses, retroviruses, and lentiviruses, have high transfection efficiencies, their potential immunogenicity, production control, and cost hinder their application. Compared with viral vectors, non-viral vectors have many advantages, such as low immunogenicity and toxicity, easy synthesis and mass production, low...

AI Technical Summary

Problems solved by technology

Cationic polymer carrier, because it complexes with nucleic acid drugs mainly through electrostatic interaction, the final complex is easily decomplexed by the polyanions that exist in large quantities in blood and extracellular fluid, so that it cannot reach the target site to achieve ideal transfection

In addition, for low-molecular-weight nucleic acid drugs (such as antisense nucleotides, siRNA and microRNA), their rigid structure and low charge density often lead to incomplete aggregation

Although these problems can be partly solved by using high charge density and polymeric carriers, it will lead to a significant increase in cytotoxicity, tissue damage and thrombus formation.

On the other hand, for nucleotides such as antisense nucleotides, siRNA and microRNA, their good water solubility and low surface charge limit the effective encapsulation, so the loading efficiency of polymers or other organic nanoparticles for such nucleic acid drugs is relatively low. Low

Images