Abstract:

Significance Because of their unique size effect, drug-loaded nanoparticles can protect drugs from being cleared by the liver and spleen, break through the physiological barrier of the human body, act directly on cells and tissues, provide local tissues with continuous high blood concentrations, enhance cell infiltration and reduce the toxicity risk of patients' normal cells. Silk fibroin (SF) has attracted much attention as a nanodrug delivery carrier material because of its excellent biocompatibility, biodegradability, low immunogenicity, high binding ability to various drugs and mild preparation conditions. In particular, SF has different functional groups, which can be chemically modified or surface modified in a variety of ways to improve the drug loading rate, trigger biological reactions to cells through covalent binding with targeted ligands, achieve targeted drug release, and improve the therapeutic efficiency. Therefore, SF is a very prospective protein as a drug-loaded base material. This paper analyzed the pelletizing principles of SF as a drug carrier material and various ways of preparing them and highlighted the mechanism of the sustained and controlled drug release of SF nanoparticles, especially introducing the smart drug release responses of SF nanoparticles to pH changes or magnetic fields, which provided a useful reference for the preparation and application of SF in drug carrier materials.

Progress SF as a drug carrier is mainly achieved by inducing or modifying the Silk Ⅰ structure to the SilkⅡ structure. The current research mainly focuses on three aspects. The first is to explore the role and mechanism of the physical and chemical properties of SF in drug-loaded nanoparticles. SF has two different secondary structures, SilkⅠ and Silk Ⅱ. By solvent treatment, such as ethanol, or under the action of high heat and high shear force, SilkⅠ transforms to Silk Ⅱ, leading to the self-assembly of SF, thus forming micro/nanospheres. The second is to study the preparation methods of SF drug-loaded nanoparticles to improve their release efficiency and morphology. At present, the main preparation methods of SF nanoparticles are precipitation, salting-out, microemulsion and desolvent methods. Nanoparticles prepared by different preparation methods also have different drug loading methods, resulting in different drug release effects. The release velocity of drug-loaded nanoparticles by encapsulation is lower than that of drug-loaded nanoparticles by adsorption. In addition, the encapsulation efficiency, release velocity and particle size were determined by the different drugs loaded. The third is to study the controlled and sustained release of SF nanoparticles. The controlled and sustained release includes two aspects: one is that the drug release curve and speed can be designed and regulated, and the other is that the drug release position can be regulated to achieve targeted release. Targeted release can significantly reduce the side effects in vivo, reduce the damage to normal cells, and improve drug utilization to obtain better efficacy. The targeted release of drugs mainly includes the pH response and magnetic response. Drugs can reach specific sites for targeted release through a magnetic field or pH change in the body to achieve controlled release of nanoparticles.

Conclusion and Prospect Through the analysis and review of the related studies on SF drug-loaded nanoparticles, the following conclusions can be obtained: ①SF is easy to extract with low cost. It has been widely used owing to its mild preparation conditions, self-assembly property, good biocompatibility and low toxicity. The prepared nanoparticles have good mechanical strength and stability, exhibiting high loading efficiency for low molecular weight drugs. ②The amphiphilic properties of SF make it possible to form nanoparticles by self-assembly, which avoids the use of cross-linking agents and other organic solvents and is expected to achieve higher utilization in vivo. ③The controlled release of SF can be achieved by adding magnetic nanoparticles or covalently binding drugs.

At present, research on SF as a drug carrier has become a hot spot, but research on the release effect and degradation rate of SF drug-loaded nanoparticles in vivo is limited. Achieving targeted release in vivo and the synergistic effect with pH in vivo and an external magnetic field may be a promising method explored in future studies. In particular, in the preparation process of SF drug-loaded nanoparticles, not only the particle morphology and drug loading rate should be considered but also the drug characteristics and release effects should be comprehensively considered so that multiple smart responses can be combined to achieve a smart nanoparticle delivery system, reduce the pain of patients, reduce the side effects of drugs, and achieve accurate medical treatment.

Key words: silk fibroin, nanoparticle, drug delivery, intelligent response, targeted drug release