Synthesis And Characterization Of Silk Fibroin Coated Drug-loaded PLGA Microspheres

1.BackgroundThe resorption of hard and soft tissue of alveolar ridge following tooth extraction is a physiological process which will become great challenge for subsequent implant placement and restoration especially in the aesthetic zone,and the method to maintaining these tissues after tooth extraction is the extraction site preservation?or Alveolar Ridge Preservation?which is a limb of GTR or GBR.^[1,2]Biphasic calcium phosphate ceramics,tricalcium phosphate bone cement,borate bioglass,and synthetic polymer materials are commonly used as bone substitute materials in the extraction site preservation.Poly[lactic-co-?glycolic acid?]?PLGA?as one of polymer materials is widely used to prepare drug delivery system and cell scaffold for bone defect due to its biocompatibility and biodegradability.PLGA as a carrier to load bone-inducing active drugs,such as simvastatin,can promote bone remodeling and new bone formation.Nevertheless,for PLGA microspheres,besides the burst release of drugs from vehicles,the hydrophobic nature,absence of the corresponding biosignaling molecule in the osteogenic process and releasing of acidic degradable byproducts from matrix limit the widespread applications^[3,4].Therefore the method to improve the imperfections of PLGA has became a prevalent study in recently^[5,6].As a natural protein,silk fibroin has good biocompatibility degradability and hydrophilicity.Biomaterials prepared with silk fibroin,such as surgical suture,have been widely used in clinical practice and has achieved good results^[7].Studies have shown that PLGA scaffold with silk fibroin coating can not only improve the surface properties of PLGA scaffolds,but also enhance its mechanical properties,neutralize acidic degradation products,and reduce the incidence of aseptic inflammation..This study aimed to complex silk fibroin membranes on the surface of simvastatin-loaded PLGA microspheres in order to give the drug-loaded microspheres the ability to hydrophilism,inhibit their burst drug release,and prolong their degradation time.Therefore,better application effects can be obtained in the extraction site preservation.2.Material and methodsSIM loaded PLGA microspheres were fabricated by single emulsion-solvent evaporation technique,then,silk fibroin was chosen as coating material to deposit on the surface of as-prepared drug loaded microspheres with ethanol treated procedure?LbL and solvent evaporation technique?or glutaraldehyde cross-linking.The characterizations was confirmed by SEM,FTIR and XRD.SIM release profiles in vitro were investigated as well.3.Result and discussion1)PLGA blank microspheres prepared by the emulsifying solvent evaporation method.The surface of the microspheres is smooth and evenly distributed dimples are observed on the surface of some microspheres.The size of blank microspheres is between6.8²9.3?m.SIM is rod-like shape and the mean length and diameter of these particles are ca.13.2?m and 4.7?m.2)The drug loading ranged from 4.05%to 16.98%.Some simvastatin crystals were observed on the surface of the higher drug loading microspheres.3)No matter silk deposition directly using ethanol or desolvation,PLGA microspheres were fused together or crashed during stirring after ethanol treatment.Modified microspheres were obtained by glutaraldehyde cross-linking method with no crashed.The size of modified microspheres is between 5³6?m.4)From the FT-IR,bands of surface-modified SIM-loaded PLGA microspheres were found at 1630 and 1541 cm^-1.5)In vitro release experiments,the release rate of silk fibroin modified drug-loaded microspheres was the slowest and the cumulative release was 37%at 24 h,which clearly better than non-modified microspheres.6)With the releasing time prolongs,holes appear on the surface of the non-modified drug-loaded microspheres and inside gradually form a shell shape.While modified drug-loaded microspheres have wrinkles on the surface.4.ConclusionIn conclusion,in this study,SIM loaded PLGA microspheres were fabricated by single emulsion-solvent evaporation technique,then,silk fibroin was chosen as coating material to deposit on the surface of as-prepared drug loaded microspheres with glutaraldehyde cross-linking.As avoid using the high concentration organic solvents,we can get the final particles with out damage.Besides,the silk coated microspheres showed better release profiles.The burst release was obviously delayed and the release duration was extended.With excellent biocompatibility,biodegradability and unique mechanical properties of silk fibroin coated PLGA drug delivery,it will have huge potential values in local delivery of stomatology.