Preparation method of photo-crosslinked chitosan-methacrylic acid nanoparticles

Abstract

The invention discloses a preparation method of photo-crosslinked chitosan-methacrylic acid nanoparticles, which comprises the following steps: S1, adding 2-methacrylic anhydride into a chitosan solution for reaction to obtain chitosan-methacrylic acid; S2, preparing a chitosan-methacrylic acid solution with a certain concentration, and adding a photoinitiator; S3, adding the solution prepared inthe S2 into a mixed oil phase of cyclohexane and n-hexanol, and adding a surfactant triton X-100 to prepare a W/O microemulsion; and S4, irradiating the microemulsion prepared in the S3 with ultraviolet light, and carrying out centrifugal separation to obtain the nanoparticles. The method is used for preparing the nanoparticles which can be encapsulate biomacromolecules such as protein and polypeptide and maintain the biological activity of the biomacromolecules.

Description

technical field [0001] The invention relates to a method for preparing nanoparticles, in particular to a method for preparing photocrosslinked chitosan-methacrylic acid nanoparticles. Background technique [0002] Chitosan is obtained by deacetylation of chitin, has a large number of free amino groups, is the site of many chemical reactions, has a positive charge on the surface, is insoluble in water and organic solvents, and is soluble in dilute acids such as acetic acid, nitric acid, and hydrochloric acid. In the field of drug delivery, chitosan has excellent properties, such as good biocompatibility, biodegradability, mucoadhesion, and non-toxicity, and can reversibly open tight junctions to facilitate paracellular transport of macromolecules. [0003] At present, many biomacromolecules, such as polypeptides, proteins and nucleic acids, are used for disease treatment, but the oral delivery of protein drugs still faces many problems. Proteins are easily destroyed by strong...

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Problems solved by technology

[0003] At present, many biomacromolecules, such as polypeptides, proteins and nucleic acids, are used for disease treatment, but the oral delivery of protein drugs still faces many problems. Proteins are easily destroyed by strong acids and digestive enzymes in the gastrointestinal tract. They have large molecular weight and are hydrophilic. strong, poor permeability in the intestinal epithelium, and the nanoparticle delivery system has been widely studied as a protein delivery system, which can protect the drug from gastrointestinal degradation, enhance mucosal adhesion, prolong the residence time of the gastrointestinal tract, and promote drug passage. intestinal mucosal absorption

[0004] Chitosan nanoparticles are usually obtained by physical cross-linking or chemical cross-linking. Physical cross-linking is based on the ion gel method, which is formed under the electrostatic interaction of chitosan and polyanionic electrolytes (such as sodium tripolyphosphate, sodium citrate, etc.) Nanoparticles, but only remain stable within a certain pH range, and the nanoparticles will be destroyed if the pH is too high or too low; chemical crosslinking usually adopts W / O emulsion method to prepare chitosan nanoparticles, adding chemical crosslinking agents such as glutaraldehyde , Genipere, etc. for chemical cross-linking. Although the nanoparticles prepared by this method generally have good sphericity and small particle size, chemical cross-linking agents generally have cytotoxicity, such as glutaraldehyde, glyoxal, etc., so they are not suitable for Encapsulation of biologically active macromolecules, and genipin is also expensive

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