Effects Of Processing Parameters On The Characteristics Of Vancomycin-loaded PLGA Microspheres Fabricated By A Shear Precipitation Procedure Using Ethanol As Polymer Antisolvent

Background:Bone infection is difficult to deal with in clinic.And anti-infection treatment is a critical component of the treatment of bone infection.However,long-term systemic antibiotics may cause serious side effects.Nowadays,topical antibiotics has attracted more and more attention.It is imperative to seek an advanced strategy to improve encapsulation of hydrophilic antibiotics in sustained release system as topical antibiotics.Aim:The aim of this study is to apply a reformative shear precipitation procedure using ethanol as polymer antisolvent in the preparation of PLGA microspheres for hydrophilic drug encapsulation.The influence of various processing parameters,including polymer concentration,volume ratio of ethanol to glycerol in the shear medium,volume of aqueous drug solution,initial drug loading,and injecting rate of the drug-polymer emulsion,on the encapsulation efficiency and characteristics of resulting microspheres were investigated.Release characteristics and biological evaluation were studied as well.Method:Scanning electron microscopy(SEM),solvent extraction technique procedure,in vitro elution method,in vitro antibacterial activity test and in vivo degradation test were carried out to to characterize the surface morphology,determine vancomycin hydrochloride loading of the vancomycin-loaded PLGA microspheres,evaluate the release behavior in vitro,describe the antimicrobial activities and represent the degradation behaviour of the vancomycin-loaded PLGA microspheres,respectively.Result:The maximum encapsulation efficiency for the resultant microspheres,who was spherical with pores on the surface as well as internal structure and has a distribution of mean diameter ranging from 11.15 to 27.51?m,is up to 89.97%.Iincreasing the polymer concentration resulted in higher encapsulation efficiency and larger mean diameter with lower drug load.Increasing initial drug loading contributed to higher encapsulation efficiency and drug load.Encapsulation efficiency and drug load decreased with increasing volume of aqueous drug solution accompanied by increased mean diameter.The microspheres size,encapsulation efficiency and drug load increased with the raising of the injecting rate of the emusion.In this work,for the incorporation of vancomycin hydrochloride into PLGA microspheres,the volume ratio of alcohol to glycerinum seem to be the key factor.In vitro antibacterial activity test,clear zones of inhibition could be seen around the samples of vancomycin-loaded PLGA microspheres.And the zones of inhibition lasted up to 7 days.Following implantation over 12 weeks,no remaining microspheres was observed from the HE staining samples,which indicated that microspheres had undergone complete degradation in the environment.Conclusion:Vancomycin-loaded PLGA microspheres were prepared by a reformative shear precipitation successfully,which was available for encapsulating hydrophilic drugs into polymer microspheres effectively.Microspheres characteristics of the microspheres could be modulated by adjusting the processing parameters.Vancomycin-loaded PLGA microspheres showed sustained release performance of vancomycin.Vancomycin can be safely encapsulated in PLGA microspheres without losing its antibacterial activity against S.aureus.Vancomycin-loaded PLGA microspheres could be degraded in the body with good biocompatibility.