The Use Of Cisplatin-loaded Mucoadhesive Nanofibers For Local Chemotherapy Of U14 Cervical Cancers In Mice

Objective: Local controlled release drug delivery system based on polymer materials has become a hot research topic, which has the advantages of enhancing efficacy and reducing side effects compared with conventional chemotherapy. In all kinds of local controlled release drug delivery system, the fiber mat made by electrospinning technology has the advantages of high specific surface area, high porosity, high drug loading and good biological adhesion. So it is widely used in the controlling release of drug. In order to evaluate the efficacy and safety of the drug, the fiber felt as drug carrier, which was used in the animal tumor model of cervical cancer, was used in this study. In order to explore a new drug carrier which is suitable for the vaginal route, to find a new way to treat cervical cancer.Method: We desigine three parts in our experimental study. First part :preparing electrostatic spinning nano fiber material containing platinum, and testing the general properties. Application of polylactic acid and polyoxyethylene through electrospinning has been synthesized hydrophilic, containing cisplatin or fluorescein sodium nanofiber mats. Construction of the in vitro vaginal mucosa system model to determine adhesion and release properties of the nanofiber mats. In the second part of the experiment, the mouse cervical cancer model was established by injecting U14 cells, and the fluorescence signal was detected by fluorescence detection. In the experiment of biological distribution, the tumor bearing mice were dissected, the tumor foci and the organs were fluorescence imaging, and the distribution of fluorescence signal was analyzed. In the third part of the experiment, based on the successful establishment of animal model we study the effect of nano fiber on the local chemical treatment of cervical cancer. The animals were grouped, the inhibition rate of tumor were analyzed to study the effect of different doses of drugs for the treatment of cervical lesions.Results: in the first part of the experiment, the cisplatin was loaded into the fiber mat, and the fiber was smooth and without crystallization. The measured results showed that the fiber felt is hydrophilic after the drug loading. And can quickly release the drug into organization. In the second part of the experiment: compared with the gel preparation, the fiber felt can ensure the high efficiency of the drug to stay in the vagina, in order to achieve effective drug concentration within the vagina to avoid the omission and waste of drugs. It provides the necessary premise for the drug to play a therapeutic role. In the experimental animal model, the cervical cancer model in situ was inoculated into mice. After 7 days, all the mice were inoculated with the mass on the cervical part of the body. Stablished success rate was 100%. In the subsequent in vivo release distribution experiments, the fluorescent signal of nano fiber was placed in the vagina, and the mice were sacrificed at different time points after implantation. The fluorescence intensity was detected in the tissues of mice. Until 24 hours later, the fluorescence signal in the vagina is weakened, other organs still can not detect the signal. To 48 h, the entire reproductive tract within the fluorescence signal metabolic clearance, only a trace of residual. In the third part of the experiment, the mice were treated with cisplatin. After the treatment, the weight of mice was measured and weighed, and the results were obtained. The results showed that under the dose of 5mg.kg-1, the tumor inhibition rate could reach 52.7%, and the average weight loss of mice in the treatment group was 2.82%, which reflects the better efficacy and safety.Conclusion: the electrostatic nano drug delivery system is proved to be a good vaginal delivery system. The excellent adhesion property of the vagina can make it stay in the vagina enough time to release drug and function in the lesion. It can realize the enrichment of the drug in the vagina, reduce the distribution of other organs, so as to reduce the toxic and side effects of chemical drugs. The drug delivery system in the vaginal delivery system has achieved a good balance in the treatment of local and systemic toxicity, and provides a feasible new way for the treatment of cervical and vaginal cancer.