Preparation Of Polylactic Acid Drug-loaded Microspheres By Foam Transfer Metho

Polylactic acid microspheres are biodegradable functional polymer materials,which can be used as drug carriers to achieve controlled release of drugs,increase drug targeting,reduce toxic side effects and improve therapeutic effect.At present,the main preparation methods of polylactic acid microspheres include emulsified solvent evaporation,phase separation,spray drying,melting and microfluidic technology.In our previous work,the research group invented a simple and efficient new technology for preparing functional polymer microspheres by foam-transfer on the basis of the traditional solvent evaporation method,and successfully applied the technology to prepare polylactic acid microspheres loaded with oil soluble drugs.Based on the above research,this paper intended to further apply the preparation method to the preparation of water-soluble drugs and water-soluble drug polylactic acid microspheres.Firstly,aspirin as a representative slightly water-soluble drug,polylactic acid-aspirin microspheres were prepared by this preparation method,and compared with traditional solvent evaporation method under the same experimental conditions,to analyze the advantages and disadvantages of foam-transfer method.Then,bovine serum albumin as the representative of water-soluble drugs,polylactic acid-bovine serum albumin microspheres were prepared by two methods.The effects of surfactants,oil/water ratio,polymer concentration and other conditions on drug-loaded microspheres were systematically studied and compared.Finally,the release and degradation properties of drug-loaded microspheres were studied systematically.The results show that:(1)Apirin as a representative water-soluble drug,PLA-as microspheres could be prepared successfully by solvent evaporation method and foam-transfer method,and the yield and encapsulation efficiency of microspheres were affected by stirring rate,polymer concentration,dosage,concentration of protective colloid,oil/water ratio and other factors.However,compared with the traditional solvent evaporation method,the foam-transfer method had less influence on the microsphere morphology and drug loading performance in terms of stirring rate,polymer concentration and dosage.In addition,under the same experimental conditions,the encapsulation efficiency of PLA-as microspheres prepared by foam-transport method was about 30% higher than that by traditional solvent evaporation method.This was mainly because the foam-transfer method,the contact time of oil-water phase was shorter than that of solvent evaporation method,which reduced the dissolution of aspirin in water and thus led to the improvement of encapsulation efficiency.When the stirring rate = 600 r/min,the concentration of PVA = 1 wt%,the polymer concentration =1:20 and the ratio of oil to water = 1:2.5,the yield of PLA-as microspheres prepared via foam-transfer method was 82.83 wt % and the encapsulation efficiency was 44.09%.(2)Bovine serum albumin as the representative water-soluble drug,PLA-BSA microspheres could be prepared successfully by solvent evaporation method and foam transport-method,and the yield and encapsulation efficiency of microspheres were affected by the dosage,surfactant,polymer concentration,oil/water ratio and other factors.However,compared with the traditional solvent evaporation method,under the same experimental conditions,the encapsulation efficiency of PLA-BSA microspheres prepared by the foam-transport method was about 3 times higher than that by the traditional solvent evaporation method.When the mass of polyethylene glycol 1000 = 0.1 g,the ratio of drug to polymer = 1:1,the content of internal water phase = 8 g,the ratio of oil to water = 1:3,and the polymer concentration = 1:25,the encapsulation efficiency of PLA-BSA microspheres prepared via foam-transport method was 40.53%,and the drug loading was26.44%.(3)The sustained release performance of PLA-as microspheres showed that the microspheres could effectively improve the cumulative release rate of drug-loaded microspheres in the sustained release medium under alkaline conditions,and the sustained release environment at too high or too low temperature was not conducive to improving the cumulative release rate of drug-loaded microspheres.The slow-release properties of PLA-BSA microspheres showed that the microspheres prepared by the foam-transport method and the traditional solvent evaporation method could be released in PBS buffer,and the cumulative release rate of the microspheres prepared by the foam-transport method was higher.The mechanical properties of the two different microspheres showed that the degradation behavior of the two different microspheres occurred during the process of soaking in the slow-release medium for 2 months.