The Synthesis Of PLGA Non-spherical Particles And The Application For Local Drug Delivery In Oral Cavity

Background Oral cavity is easily stimulated by various internal and external factors inducing various oral tissue diseases,due to the complexity of its anatomical structure,the diversity of its functions and the particularity of its environment.In addition to hard dental tissues,traditional local administration of drugs for mucosal and periodontal diseases has low bioavailability,which is caused by the complicated oral environment.Therefore,various drug delivery systems are urgently needed to be developed for local administration in oral cavity.It is recognized that shape and surface topography of drug carriers have significant effect in drug release kinetics,interfacial behaviors and biological responses.Studies have shown that the shape and surface topography of the carrier can regulate phagocytosis,promote tissue adhesion,improve drug loading and drug release,and regulate the distribution of particles in vivo.Therefore,it is expected to improve the bioavailability of local drugs and improve the therapeutic effect by using the shape and surface topography of the carrier to load related drugs for oral diseases.In this study,we prepared PLGA non-spherical particles with coarse surface by double emulsion-solvent evaporation technique and loaded simvastatin for alveolar ridge preservation,which provided theoretical support for clinical application in the future.Besides,bFGF and tetracaine loaded PLGA non-spherical particles were fabricated for the treatment of oral mucosal trauma.MethodsPLGA non-spherical particles with coarse surface were fabricated by double emulsionsolvent evaporation technique and the morphology of the particles was controlled by the control variable method.Combining with the characterization results of scanning electron microscope(SEM),the formation mechanism of PLGA non-spherical particles was discussed.The osteogenic drug simvastatin was added to the oil phase to get the SIM loaded PLGA non-spherical particles.The physical and chemical properties of the particles were analyzed by SEM,FTIR,XRD,DSC and other characterization methods.In vitro release experiments were conducted to investigate the effects of the morphology of the carrier and the type of release medium on the drug release kinetics.Besides,combined loading of bFGF and tetracaine on PLGA non-spherical particles for the treatment of oral mucosal ulcers.In vitro and in vivo experiments were conducted to verify their ability to promote trauma healing.Results(1)Parameters such as type and concentration of porogen,volume ratio of internal water phase to oil phase,homogenization speed and mixing speed of external water phase all participate in the regulation of the morphology of non-spherical particles,among which ammonium bicarbonate plays a leading role.The corresponding formation mechanism was proposed based on porous hollow microspheres collapse in the emulsion system accompanying strong shear effect.(2)PLGA non-spherical particles can accelerate hemostasis.Drug loading and encapsulation of non-spherical particles were lower,and drug release rate was faster.In addition,different release media also affected the drug release kinetics.(3)The drug delivery system may be broken by high rate of tetracaine.The effect of tetracaine on carrier material can be reduced by increasing the proportion of PLGA.bFGF-tetracaine loaded non-spherical particles can promote the proliferation and migration of fibroblasts and promote the healing of rat oral ulcer.ConclusionPLGA non-spherical particles with coarse surface can be fabricated by double emulsion-solvent evaporation technique,and the corresponding formation mechanism was proposed based on porous hollow microspheres collapse by strong shear effect.PLGA non-spherical particles can accelerate hemostasis and load different drugs,which is expected to be used as a new carrier to prepare various drug delivery systems for the treatment of oral diseases through local administration.