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Preparation Of Controlled-release PLA/MSM Microspheres For The Therapy Of Osteoarthritis

Posted on:2014-01-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:X Z WangFull Text:PDF
GTID:1224330395496831Subject:Surgery
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In recent decades, the progress of the release microspheres to promote the developmentof cartilage tissue engineering. Preparation of microspheres materials for natural materialsand synthetic polymer materials, including PLA, PLGA has good biocompatibility,degradation and absorption characteristics, is recognized as an excellent biodegradablepolymer materials, environmental protection, tissue engineering, fracture fixation andcontrolled drug release and other fields are widely used[4-7]. Further, methyl sulfonylmethane (MSM) is an organic sulfide, and the necessary material for synthetic humancollagen. Meanwhile, as a common health drugs, mainly used for the repair treatment of theskin, hair, bone, cartilage, and the like. Mainly used in the clinical treatment of osteoarthritis[8-10]. Therefore, the preparation of PLA/MSM drug-loaded microspheres has good releaseproperties and biological activity, as long-acting release formulation of the MSM is used inthe treatment of osteoarthritis and bone and cartilage tissue engineering research.The prepared bioactive release microspheres, on the one hand, this study differentpolylactic acid content of blank microspheres prepared by membrane emulsification, andwere characterized by scanning electron microscopy, and to explore the different surfactantthe impact of the concentration on the structure of the microspheres, and stirring speed onthe size of the microspheres. The present study also prepared sustained-release microspheres,cheap and easy to obtain a small molecule compounds having biological activity isintroduced, dimethyl sulfone. To explore the effects of different membrane pore size anddimethyl sulfone content on microsphere size, morphology, drug loading, encapsulationefficiency and release behavior and cell proliferation. In addition, in recent years, localsustained release drug delivery system caused due to the unique properties of the scholars ofconsiderable concern, this study will also release microspheres prepared for rabbitosteoarthritis treatment, to evaluate the biological effects. PLA/MSM release microspheresprovide experimental evidence for the clinical application and development of bioactivecheap cartilage tissue engineering scaffolds.The first part of the film emulsion prepared blank polylactic acid microspheres.Preliminary work in this experiment, completely independent exploration of variousexperimental parameters. Membrane emulsification were prepared by varying the content of the polylactic acid blank microspheres, polylactic acid content of1wt%,3wt%,5wt%,respectively. The surface morphology and particle size of the microspheres using scanningelectron microscopy. Different continuous phase flow rate, pressure and concentration ofsurfactant on the morphology and size of the microspheres. Continuous phase velocityrespectively300,500,700,900rpm, and the surfactant concentration respectively of0.5,1,2,4,6g/l. The results show that: the smooth surface morphology of microspheres ofuniform size distribution better. When the polylactic acid content of3wt.%, Shows a bettermorphology and distribution, the size of the microspheres with the continuous phase velocityincreases and decreases, the pressure and the size of the aperture of the film, the greater themembrane pore pressure increases required large.The second part of the polylactic acid (PLA) microspheres carryingMethylsulfonylmethane(MSM) were prepared by membrane emulsification in thispaper.The effects of membrane pore size, stirring speed and MSM concentration onmicrospheres morphology,size,drug loading and in vitro release,as well as cell biologicalactivity were studied using ESEM,ICP-AES,in vitro culture of MC3T3-E1cell and MTTmethod。The study will provide references for the study of the long-acting release agent ofMSM.The results showed that the drug-loaded microspheres prepared with membraneemulsification were typical spherical with smooth surface and the internal porousstructure.The size and morphology of the microspheres could be affected by membrane poresize, stirring speed and MSM concentration.The drug-loaded microspheres prepared withthe membrane pore size of5.1μm and a stirring speed of500rpm were more uniform in sizethan others.When the concentration of MSM solution was8.6wt.%, the drug loading ofmicrospheres could be up to77.43%.The in vitro release rate of MSM could be sped upwhen the membrane pore size was reduced and the MSM concentration was increased, butthe initial burst release for all samples was not obvious, and it reached up to89.2%after10d.Cell experiments showed that cell proliferation of MC3T3-E1was improved at7d cellculture using MSM-loaded microspheres of5.1μm and8.6wt.%.The research indicate thatthe PLA/MSM drug-loaded microspheres has good controlled release characteristics andbiological activity, which can be used as a long-acting release formulation of MSM for thetreatment of osteoarthritis and application in bone and cartilage tissue engineering.The third part of the PLA/MSM release microspheres in rabbit osteoarthritis. Preliminary work to prepare the PLA/MSM release microspheres of this study was toinvestigate the impact of different the MSM content on cartilage repair. First, theestablishment of rabbit knee osteoarthritis models to establish model4w MRI observation ofarticular cartilage changes confirm the success of the model, and then the local MSM contentloaded microspheres injected into the rabbit knee joint cavity week to drugs. Air embolismnine weeks after the administration of the animals were sacrificed, the general assessment ofcartilage defects and repair capacity of local anatomical knee, using the Makin ratings andInk scores assessed, collected synovial fluid for Giemsa staining and ELISA kit hyaluronicacid, interleukin-1, tumor necrosis factor-α detection, and synovial tissue and cartilage tissueHE staining. The results show that: the MSM content is0.9wt.%better repair capacity, caneffectively promote cartilage repair.
Keywords/Search Tags:MSM, PLA, sustained-release microspheres, membrane emulsification, osteoarthritis, cartilage defects, repair
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