Preparation Of PBAT Microspheres And Their Drug-carrying Application Researc

The stable release of anticancer drugs in vivo can effectively improve its therapeutic effect,and the stable release of drugs requires a carrier with stable release function,which does not affect its efficacy and can be effectively degraded in vivo.In this study,biodegradable Poly(butyleneadipate-co-terephthalate)(PBAT)hollow microspheres were prepared by electrostatic spray method,and polymer materials that promote the degradation of microspheres were added to modify them into biodegradable new micron-sized hollow microspheres.The anti-cancer drug treatment of lung cancer and its sustained release performance were detected in vitro and in vivo to improve the targeted treatment efficiency of lung cancer.The main research contents and results are as follows.Chapter 1: Firstly,the current research status and urgent needs of drug delivery systems are summarized.Then,the preparation materials,advantages,research and application in the field of medicine of biodegradable polymer microspheres were reviewed.Then the development process and principle of electrostatic spray technology and the influencing factors in the preparation of polymer microspheres are briefly introduced.Chapter 2: The optimum process of preparing PBAT microspheres by electrostatic spray method was explored by single factor experiment.The morphology and particle size distribution of the microspheres were investigated by scanning electron microscopy.The optimum preparation conditions were determined as follows:ethanol receiving,5 wt% PBAT dichloromethane solution,solution flow rate of 2.0m L/h,16 k V voltage,20 G needle and 20 cm receiving distance.The average particle size of PBAT microspheres prepared under these conditions was 12.19 ± 1.34 μm,and the relative standard deviation(RSD)value was 11.02%.Secondly,scanning electron microscope(SEM)images were taken by intercepting the cross section of PBAT microspheres,and it was found that the interior of the microspheres was a hollow porous structure.Chapter 3: Polyvinyl pyrrolidone(PVP)and polyvinyl butyral(PVB)were added to PBAT solution to prepare modified PBAT microspheres.When the amount of PVB and PVP added reached a mass ratio of one fifth,it did not significantly affect the uniformity of PBAT microspheres.After three weeks of in vitro degradation experiments,it was found that both modified microspheres had different degrees of degradation.The degradation rate of PBAT/PVP microspheres was 38.68%,the degradation rate of PBAT/PVB microspheres was 19.44%,and the degradation rate of pure PBAT microspheres was 15.18%,which indicated that the degradation performance of PBAT/PVP microspheres was more significant.The internal structure of PBAT,PBAT/PVP and PBAT/PVB microspheres was observed by SEM,and there was no significant change in the internal structure of the hollow multi-channel.Therefore,it was confirmed that the addition of PVP to PBAT solution could effectively promote the degradation of PBAT microspheres without affecting the internal structure of the hollow and porous channels.Erlotinib,a specific targeted drug for lung cancer,was loaded into the prepared PBAT,PBAT/PVP and PBAT/PVB microspheres by electrostatic spray method.The specific targeted drug Erlotinib for lung cancer was loaded into the prepared PBAT,PBAT/PVP and PBAT/PVB microspheres by electrostatic spray method.The loading performance and in vitro release effect of the three microspheres on Erlotinib were studied by inverted fluorescence microscope,UV-visible absorption spectroscopy,differential scanning calorimeter,thermogravimetric analysis and infrared spectroscopy.The results showed that Erlotinib was successfully loaded onto PBAT,PBAT/PVB and PBAT/PVP microspheres.The encapsulation efficiency was 92.13%,91.52% and91.8%,respectively.After three weeks of in vitro release,it was found that the cumulative release of Erlotinib in PBAT,PBAT/PVB and PBAT/PVP drug-loaded microspheres was 31.81%,46.42% and 78.55%,respectively,and the drug release of PBAT/PVP drug-loaded microspheres was more stable,indicating that the cumulative release of drug-loaded PBAT/PVP microspheres was significantly higher than that of the other two drug-loaded microspheres,and the release concentration was more stable.Chapter 4: The PBAT/PVP microspheres loaded with Erlotinib were subjected to anti-tumor experiments in vitro and in vivo.MTT assay showed that PBAT/PVP microspheres had no significant inhibitory activity on the growth of normal cells and cancer cells.After A549 cells were treated with Erlotinib-loaded PBAT and PBAT/PVP microspheres for 72 h and 96 h,the inhibitory activity of Erlotinib-loaded PBAT/PVP microspheres on the growth of cancer cells was significantly(greater than4 mg/m L,*p < 0.05).The mouse model of transplanted tumor was used to inject drug-loaded microspheres into the tumor of mice,and the changes of various physiological indexes of mice at different time after injection were detected.Three weeks later,the mice were dissected,and the main organs and tumor tissues were taken to detect the pathological changes of each organ and the expression of Ki67,the target protein of Erlotinib in tumor tissues.The results showed that the drug-loaded PBAT/PVP microsphere treatment group had a more significant effect than the drugloaded PBAT microsphere and Erlotinib treatment group(*p < 0.05).There was no significant difference in tissues and organs of mice in each group(#p > 0.05).The expression of Ki67 in tumor tissues showed that the protein expression of PBAT/PVP microspheres was significantly lower than that of other groups(***p < 0.001).This indicates that PBAT/PVP microspheres loaded with Erlotinib can effectively promote its targeting in the treatment of lung cancer and improve the therapeutic effect of lung cancer.Through the above research,we successfully prepared a hollow microsphere that can load Erlotinib,a targeted anti-cancer drug for lung cancer,and can degrade and promote its therapeutic effect.