| At present,bio based materials are in a flourishing stage of development and are widely used in the food industry,agriculture,and biopharmaceutical fields.Among them,polylactic acid(PLA),as the most commonly studied bio based polyester polymer material,has excellent advantages such as biodegradability,biocompatibility,and ease of processing.It has attracted attention in biomedical fields such as drug sustained-release and tissue engineering materials.However,it has defects such as high hydrophobicity of the material surface and difficulty in controlling the degradation cycle,which greatly limits the application of PLA in the biological field.Therefore,this study conducted a series of modifications to PLA in order to better apply it as a drug sustained-release carrier.The specific research work is as follows:(1)This article uses PLA as the substrate and prepares PLA microspheres with controllable particle size through emulsification solvent evaporation method combined with an external constant flow dripping device.The optimal preparation process conditions were optimized and determined through orthogonal experiments using particle size as the evaluation index.The oil phase constant droplet acceleration was 60 m L/h,stirring speed was 1000 r/min,PVA concentration was 1.25%,PLA concentration was 7.5%,and water oil phase volume ratio was 8:1.The microspheres were observed to have good sphericity and no adhesion under a microscope.(2)Based on the opposite charge properties of sulfated carboxymethyl cellulose sodium(SCMC)and chitosan(CS),as well as their good hydrophilicity and biocompatibility,a large number of amino groups on ethylenediamine were utilized to produce an aminolysis reaction with ester bonds in the PLA molecular chain,successfully introducing amino groups to the surface of PLA.Subsequently,by combining electrostatic layer by layer assembly technology,SCMC and CS were alternately deposited on the surface of PLA microspheres to prepare a PLA/SCMC/CS composite microspheres,which improved the hydrophilicity of PLA microspheres.The successful introduction of amino groups was demonstrated through infrared absorption spectroscopy and determination of amino group content;Through the contact angle test and the UV absorbance test of the fluorescent labeled chitosan layer,it proved the formation of the PLA/SCMC/CS composite microspheres multilayer structure,explored the influence of polyelectrolyte selfassembly time,concentration and charge content on the multilayer composite structure,and realized the successful preparation of multilayer polyelectrolyte composite structure;By measuring the contact angle,weight loss,and water absorption of the microspheres,as well as the lactic acid content in the degradation solution,it was proved that the hydrophilic and degradation properties of PLA/SCMC/CS composite microspheres were superior to PLA microspheres,and the hydrophilic modification was successful.(3)The successfully modified PLA/SCMC/CS composite microspheres were applied to drug sustained-release studies.PLA microspheres were used as the control group to investigate the drug loading and encapsulation efficiency of the two microspheres.The study showed that the drug loading capacity and encapsulation efficiency of the composite microspheres(10.64 ± 0.24)% and(70.63 ± 1.71)% were higher than those of PLA microspheres(3.82 ± 0.21)% and(23.02 ± 1.43)%,respectively.At the same time,the sustained release performance and drug release mechanism of PLA/SCMC/CS composite microspheres were investigated.Due to the presence of amino hydrophilic groups and a multi-layer composite membrane structure on the surface of PLA/SCMC/CS composite microspheres,and the smaller specific surface area,their sustained release performance for hydrophilic drugs is superior to that of PLA microspheres.The results of in vitro drug release studies indicate that the in vitro release models of the two microspheres are most in line with the Ritger-Peppas kinetic equation,and the composite microspheres mainly release drugs through the Fick diffusion mechanism.The above series of studies indicate that PLA microspheres with more controllable particle size can be obtained by improving preparation methods and performance.Based on this,PLA/SCMC/CS composite microspheres prepared exhibit better hydrophilicity and more stable degradation performance,demonstrating great potential for application in the field of hydrophilic drug sustained-release. |