Temperature-sensitive pH-sensitive drug-carrying microspheres and preparation method and application thereof

Abstract

The invention discloses temperature-sensitive pH-sensitive drug-carrying microspheres and a preparation method and application thereof. According to the preparation method herein, chitosan and a crosslinker are subjected to chemical bond connection through chemical crosslinking to form microspheres; the preparation method has mild conditions, and is simple to perform and feasible; chemical bond immobilization enables mechanical strength of the microspheres to be improved, and encapsulation rate is higher; the microspheres herein are suitable for carrying proteins, polypeptides and amino acid drugs; the microspheres have no need for special, complex purification steps and have good slow-release effect.

Description

technical field [0001] The invention belongs to the field of preparation of drug slow-release carriers, and in particular relates to temperature-sensitive and pH-sensitive drug-loaded microspheres and a preparation method and application thereof. Background technique [0002] The drug sustained-release system is to use physical or chemical methods to combine drugs and carrier materials, and release them into the human body environment at a certain rate within a certain period of time or transport them to specific target tissues, so that the drugs can play a role in the health of the body. Slow therapeutic effect, the drug is adsorbed to the surface of the carrier or embedded in the carrier through coating, chemical or physical connection, and the drug can be released through drug diffusion, medium penetration and degradation of the carrier itself, so compared with the traditional drug delivery system , The drug controlled release system has remarkable excellent characteristi...

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Problems solved by technology

[0004] Existing methods for preparing chitosan microspheres include emulsification cross-linking, chemical cross-linking, ion gel, spray drying, coagulation, etc. Emulsion cross-linking is a traditional method for preparing microspheres. This method uses aldehyde compounds to react with amino groups on chitosan molecules in the oil / water phase to form chemical bond-cured microspheres, but the particle size of the prepared microspheres is relatively large, and the oil phase on the surface of the microspheres is difficult to remove; The ion gel method is a method of forming microspheres through the electrostatic interaction force between polyanions and polycations. The amino groups in chitosan molecules are protonated and combined with polyanions (such as sodium tripolyphosphate, tetrapolyphosphate , octapolyphosphate, etc.) are cross-linked to form microspheres under electrostatic action. The preparation conditions of this method are mild, but the obtained microspheres have poor mechanical strength and low encapsulation efficiency

[0005] Existing methods for preparing chemically cross-linked chitosan microspheres, such as the Zhejiang University master thesis published in 2014, "Cross-linking of genipin, glutaraldehyde or EDC / NHS on the construction of collagen / chitosan dermal scaffolds role", the method disclosed in this paper is to use glutaraldehyde as a cross-linking agent to prepare a collagen / chitosan scaffold by chemical cross-linking. The disadvantage of this method is that it has strong cytotoxicity and will cause harm to the human body.

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