Preparation Of Polylactic Acid And Its Copolymer Microspheres And Its Application In The Field Of Biomedicine

The microspheres prepared by polylactic acid and its copolymers have good biocompatibility and biodegradability,and have broad application prospects in biomedical fields such as tissue engineering and embolization therapy.However,pure microspheres have their drawbacks,such as hydrophobicity,low biological activity,and fewer cell binding sites.In recent years,the surface of microspheres has been modified to increase its hydrophilic properties and biological activity.It has become a research focus in polylactic acid materials applications.With the development of biology and medical science,the use of microspheres as carriers to encapsulate drugs,proteins and nanoparticles has become a new trend in microspheres' application,which also gives polylactic acid microspheres vitality.In this thesis,we have carried out three aspects of research.Firstly,polylactic acid-glycolic acid(PLGA)copolymer was used as raw material to prepare PLGA microspheres,which are combined with chitosan/sodium alginate nanoparticles to form a micro-nano composite structure for bone regeneration treatment;secondly,Racemic polylactic acid(PDLLA 50:50)is used as a raw material to prepare porous microspheres,and the surface of the microspheres is modified by hydrolysis,thereby improving the cell compatibility of the microspheres surface;finally,the racemic polylactic acid(PDLLA50:50)was used as raw material to prepare microspheres with different morphologies,which been used as drugcarrier for hydrochloride-doxorubicin.(1)PLGA solid microspheres were prepared by the emulsion solvent volatilization method.During the preparation of the microspheres,the particle size of the microspheres can be controlled by changing the stirring method,stirring speed,and water-oil ratio.The particle size of the microspheres we obtained was in the range of 50-100?m.We used polyethyleneimine(PEI)to surface treatment of the microspheres.At this time,the surface of the microspheres has a large amount of positive amino charges,and then micro-nano composite with the chitosan/sodium alginate nanoparticles was formed due to the strong electrostatic interactions.We have made corresponding characterizations for microspheres,nanoparticles and micro-nano composite microspheres.We can clearly observe that the nanoparticles have firmly adhered to the surface of the microspheres via SEM images.Due to the strong side effects of PEI,we have done cytotoxicity tests on the microspheres under several conditions.The cells used are bone cells MC3T3.The results show that the PEI used at this concentration and in this case is cytotoxic to MC3T3.The results showed that micro-nano composite microspheres have shown a promoting effect.As a result PLGA the micro-nano structure of microspheres combined with chitosan /alginate nanoparticles is expected to be applied to bone tissue repair.(2)The porous polylactic acid microspheres were immersed in sodium hydroxide aqueous solution and the soaking time and concentration were optimized.The final optimization conditions were as follows: concentration 0.1 M sodium hydroxide,immersion time 30 min,under this condition,the porous microspheres were not damaged and hydroxyl groups were introduced on the surface.Compared with the original microspheres,the roughness of PLA porous microspheres increased,the contact angle decreased and the porosity increased,so it also showed stronger hydrophilicity,and the cells grow faster on the hydrolyzed microspheres.This work provides convenience for improving the good application of porous PLA microspheres in biomedical field.(3)Using racemic polylactic acid PDLLA as the raw material,we prepared four microspheres with different morphologies and explored their encapsulation capacity for doxorubicin drugs.We first prepared solid microspheres and porous microspheres with dichloromethane as solvent;secondly,we prepared hollow and hollow porous microspheres with ethyl acetate as solvent;finally,the effect of polymer solution concentration on the morphology and structure of microspheres was studied.The results showed that when dichloromethane was used as solvent,polymer concentration had no significant effect on the morphology of microspheres.When ethyl acetate was used as solvent,polymer concentration had obvious effect on the morphology and structure of microspheres.For dented microspheres,we determined the optimal ratio of 250 mg PDLLA /4 mL ethyl acetate.On this basis,three methods of preparing drug-loaded microspheres were explored : The first method is to use the microspheres to encapsulate the doxorubicin by shrink under the existence of high temperature and ethanol.However,the encapsulation efficiency is much lower than we expect;secondly,through charge adsorption,sodium polystyrene sulfonate and doxorubicin were used to deliver the drug,but the drug loading was still too low;lastly,Third,using four kinds of microspheres with different morphology and structure,doxorubicin was added to prepare the drug loaded microspheres directly,which was better than the first two methods.The results of ultraviolet spectroscopy and optical microscopy showed that the encapsulation efficiency and drug loading of the hollow drug-loaded microspheres were the highest among the four structural microspheres,followed by the hollow porous drug-loaded microspheres.This part provides a variety of options for the application of microspheres in transcatheter arterial embolization.