Construction And Performance Evaluation Of Alginate/pNIPAM Core-shell Microspheres Loaded With Andrographolide

Andrographolide?AND?,which is extracted from andrographis paniculata,has excellent effectivenes in the treatment of respiratory tract infections because of its antibacterial and anti-virus effects,but oral administration often results in poor patient compliance due to its bitterness.In response to the above problems,we intend to adopt the electrostatic dropled-coupled monomer polymerization process,using Alginate?Alg?as the matrix material,N-iso-propylacrylamide?NIPAM?as the monomer for shell polymerization and Andrographolid?AND?for drug model to prepare a kind of core-shell structure microspheres with stable drug loading and controlled release properties.The diversity in coordination mechanism between sodium alginate?Na-Alg?and different metal ions leads to significant differences in the structure and properties of the formed alginate gel.In this paper,the core-shell microspheres of Ca-Alg/pNIPAM and Ba-Alg/pNIPAM has been prepared using Ca²⁺and Ba²⁺as crosslinker respectively.The characteristics of microspheres were characterized by optical microscope,scanning electron microscopy?SEM?,flourier transformation infrared spectroscopy?FTIR?and thermogravimetic analysis?TGA?.The pH and temperature sensitivity of microspheres were investigated by swelling and drug release test in vitro.The biocompatibility of the composite thermosensitive hydrogel was evaluated by using the mouse fibroblast L929 as the model cell.The main conclusions are as follows:1.Preparation and Characterization of Ca-Alg/pNIPAM Core-Shell MicrospheresThe preparation process of Ca-Alg/pNIPAM core-shell microspheres was optimized by response surface design.The optimal process formula was:C_Na-Alg=17 g/L,C_Ca2+=22 g/L,C_NIPAM=120 g/L.The microspheres prepared under the optimal process have uniform particle size and excellent monodispersity,and the encapsulation efficiency is 82.57±0.15%.Compared with Ca-Alg microspheres,the core and shell structure of Ca-Alg/pNIPAM microspheres are clearly defined.The three-dimensional network structure of the microsphere matrix provides the basis for the large load of the drug,and the dense shell structure can effectively limit the drug diffusion rate.The taste mask experiment and compression test show that the introduction of the shell pNIPAM molecular chain can not only enhance the mask of the microsphere but also enhances the mechanical properties of the microspheres;2.Preparation and characterization of Ba-Alg/pNIPAM Core-Shell MicrospheresA kind of Ba-Alg/pNIPAM microspheres with core-shell structure were prepared with Ba²⁺as crosslinker.The section morphology of Ba-Alg microspheres presented square shaped dense network,while the introduction of pNIPAM results in obvious core-shell structure,and the shell becomes a dense strip network structure.The compressive modulus of elasticity of the microspheres increased from 0.703 Mpa to 1.305 MPa when the concentration of NIPAM changed in the range of 0-120 g/L,indicating that controlling the NIPAM concentration can adjust the length and number of pNIPAM chains in the microsphereshell,which has a significant effect on the mechanical strength of the microspheres.3.Drug release behavior and biocompatibility evaluation of drug-loaded microspheresThe swelling behavior of the microspheres in deionized water proved that pNIPAM in the shell structure imparts temperature-sensitive response characteristics to the core-shell microspheres.The cumulative drug release rate of drug-loaded core-shell microspheres in simulated gastric fluid was less than 10%within 2 hours,while it was rapidly released in simulated intestinal fluid and reached the release equilibrium within 10 hours.The release profiles of core-shell microspheres in simulated intestinal fluid were fitted by different drug release models.It was found that the release curves of Ca-Alg/pNIPAM and Ba-Alg/pNIPAM microspheres were consistent with Peppas mode in which the drug diffusion and matrix dissolution are coexisted.Using L929 cells as a model,the indirect contact and direct contact experiments showed that the microsphere carrier had good biocompatibility by MTT..Therefore,the core-shell microsphere carrier prepared herein has no obvious cytotoxicity and can be used in a drug controlled release system.