Composite Fiber Membrane Loaded With MBGNs@5-FU For Skin Malignant Melanoma Treatment Research

Skin malignant melanoma is one of the most common skin cancers.At present,the most common clinical treatment for melanoma is surgery.However,how to effectively inhibit tumor recurrence and promote tissue healing in the postoperative area after tumor resection is challenging.Therefore,the integration of skin wound repair and the inhibition of residual tumor growth after operation is the main research goal for this project.Multifunctional dressings loaded with antitumor drugs are a feasible strategy to achieve this goal.Electrospun fibrous membranes have a three-dimensional network structure with high specific surface area,which are similar to that of extracellular matrix.They are widely used in drug carriers and wound dressings.The fibrous membrane enabled the exchange of oxygen and nutrients,hence avoiding secondary damage to the wound surface.Furthermore,by adjusting the diameter,composition and other factors of fiber,the drug release properties could be easily adjusted.and control the drug release Therefore,this thesis carried out the study of using coaxial co-spun core-shell fibers to coat 5-fluorouracil(5-FU)in the treatment of melanoma and the promotion of skin wound healing.The specific work is as follows:1)MBGNs@5-FU was obtained by loading 5-FU with mesoporous bioactive glass(MBGNs).Subsequently,MBGNs@5-FU was dispersed into polyvinylpyrrolidone(PVP)solution to obtain the core layer,and biodegradable lactic acid-glycolic acid copolymer(PLGA)was used as the shell layer to construct multifunctional composites by coaxial electrospinning technology.The controlled release of 5-FU was achieved,which effectively improved the distribution of the drug in vivo,realized the continuous local administration of the drug at the tumor site,and finally enhances the efficacy of 5-FU.It was found that the release rate of calcium ions from MBGNs was faster than that of silica ions in acidic PBS(p H=5.0)buffer,and the cumulative release concentrations of calcium and silica were 21.822 ppm and 15.509 ppm in 9 days,respectively.The loading of MBGNs@5-FU into the core layer of core-shell fibers could achieve slow drug release,and 2% of MBGNs@5-FU fibrous membranes were able to achieve sustained release for at least 30 hours before plateauing.2)The fibrous membrane loaded with MBGNs@5-FU was covered on the skin wound to achieve the repair of skin wounds while inhibiting tumor recurrence.It was foundfound that the introduction of MBGNs facilitated migration of L929 cells.The x M@5-FU(x=2,5)group had a significant in vitro chemotherapeutic effect and could effectively inhibit the migration of B16 cells.For in vivo study,different fibrous membranes were placed on the wound defect in tumor site,and 2M@5-FU showed an excellent tumor inhibition effect.Furthermore,it also promoted postoperative wound repair.In summary,in this study,the anti-tumor chemotherapeutic drug 5-FU was loaded with MBGNs coaxial electrospinning technology,which not only prevents tumor recurrence after melanoma tumor surgery,but also promotes the rapid healing of skin wounds,confirming the feasibility and effectiveness of the multifunctional designed composite fiber membrane as a dressing for skin tumor treatment.