An Experimental Study On The Antitumor Effect Of RAd-p53PLGA Sustained Release Microsphere Combined Calcium Phosphate Cement

Objectives: The paper studies the antitumor properties of rAd-p53-PLGA–CPCand explores the possibility of making new biological carried antitumor bone packingmaterials.CPC is the bone filling restoration material for self curing. With finebiocompatibility and osteoconduction, it can assimilate and degrade in the body andbe replaced by regenerative bone. It is different from PMMA, which has high feverduring curable polymerization. Besides, it has pores between particles, so it is oftenused as good drug carrier for polypeptide and biological drugs. Loading antitumormedicine into CPC can both repair bone defects and kill the epibiotic tumor cells. Thedefects filling after bone tumor excision is one of the hot issues for bone packingmaterial.P53gene is one of the medically approved tumor suppressor genes, whosemutation is concerned with60%of the human tumor. rAd-p53is the medicine for tumortreatment carried by human p53adenovirus gene and is characterized by high securityand transfection efficiency, etc. It is a kind of broad-spectrum anti-cancer productswhich can obviously suppress the growth or specifically cause the apoptosis of tumorcell without hurting other normal cells. rAd-p53can efficiently stimuli organism togenerate the specific antitumor immune response. Local injection has a good applicationto tumor destruction cells so as to kill the tumor organizations.This research aims at discussing the method of combining bone filling materialwith antitumor activity, namely, recombinant Human Ad-p53—CPC antitumorcompound bone cement, so as to obtain some antitumor compound bone filling materialwith certain bearing capacity. Namely, this research discusses the sustained releasemicrosphere of rAd-p53PLGA, and the combination of Sustained-release Granules with CPC so as to study the in vitro release, activity and antitumor efficiency of the medicinein the combined antitumor composite artificial bone cement. Besides, it is the discussionof the tumor inhibition of antitumor composite artificial bone cement by animalexperiment and in vitro experiment.Methods: The experiment can be divided into3stages. First, make the sustainedrelease microsphere of Ad-p53PLGA by w/o/o, and observe its form with opticalmicroscope; second, compound the microsphere (8%quality percentage) with CPC,observe its form after compounding, and in vitro analysis the sustained release of thecompound medicine. Third, implant the compound into a tumor-burdened nude mousemodel and conduct the contrast experiment to specify the tumor-inhibition function ofthe compound.Results:1.The production process is simple with fine stability by w/o/o, PLGAas the medicine carrier material to make the rAd-p53PLGA sustained releasemicrosphere with regular shape, smooth surface, uniform distribution and no clearadhesion. The PLGA sustained release microsphere produced by this method releaselittle and fast at beginning, stable at the late period. It mainly slowly releases drugs,which can last for12more days.2. The slow-release medicine system carried by CPCcan make the local drugs high concentrated, stable, lasting and controllable during therelease progress. This system can slowly release Recombinant Human Ad-p53for12days with little Initial burst release possibility. Recombinant Human Ad-p53PLGAsustained release liquid, with great cancer inhibition, can efficiently suppress theproliferation of gastric cancer cells.3. rAd-p53PLGA sustained release microsphereCPC compound bone cement can suppress the growth of gastric carcinoma transplantedtumor in nude mice. It is expected to be part of comprehensive cancer therapy andHuman Ad-p53-CPC antitumor compound bone. Ad-p53-PLGA-CPC is a kind of newfunctional bone cement combined the function as drug therapy, bone repair filler and isexpected to be good bone filler after tumor resection.Conclusion: Carried by degradable polymer PLGA, Ad-p53can be made intosustained release microsphere with simple and practical craft and good stability. RAd-p53can be released from PLGA persistently and stably. RAd-p53-PLGA-CPCcan provide perfect sustained release effect and CPC sustained release liquid canefficiently suppress the proliferation of gastric cancer cells. RAd-p53-PLGA-CPC cansuppress the growth and invasion of gastric carcinoma transplanted tumor in nude mice.RAd-p53-PLGA-CPC in this experiment combines the function of antitumor and bonedefect repair and paves a new way for postoperative bone defects and strengtheningtreatment of vertebral metastatic vertebral tumor percutaneous minimally invasivevertebral. It is expected to become a bone packing material with antitumor function.The new ideas of the research: Ad-p53PLGA sustained release microsphereCPC compound bone cement not only plays the function of reconstruction after tumorsurgery, but also the antitumor function for a long time. It can be used both in the limbstumor and the reconstruction of spinal tumor surgery (such as PKP, PVP). It has broadclinical application prospects and paves the way for other later studies. It is expected toinject the mixture in the tumor bone and tumor centrums to effectively kill the tumorcell and induce the bone substitute as well. And last it comes to the reverse of bonetumor. It can reduce the possibility for amputation.