Establishment And Performance Evaluation Of Vancomycin Sustained And Controlled Release Drug Delivery System

Research on the sustained-controlled-release drug delivery system was an important direction in the field of pharmacy.Compared with conventional preparations,drug delivery system could maintain the in vivo drug effective concentration a long time,decrease dose of drug,improve drug effectiveness and safety;deliver drug to specific target organs and improve the physical and chemical properties and pharmacological activity of drug in a way.In inflammatory disease,osteoarthritis(OA)is one of the common arthritis with high attack rate and long treatment cycles.Vancomycin(Van),one of the most effective drugs,has the ability to treat bone and soft tissue trauma infection.However,the application of antibiotic for bacteria infection cannot maintain long term effective antibacterial concentration because of fast metabolism.If reused,it may bring a lot of pain,drug resistance and improved cost to the patients.Therefore,the sustained-controlled-release preparation is better to heal OA and the study of bone and cartilage tissue engineering.Thus,developing a new sustained-controlled-release drug delivery system by the aid of special carriers with specific functions is very important.A good carrier can not only improve the targeting and utilization rate of Van with the decrease of dose of subcutaneous injection,but also improve the compliance of patients and protect the drug from destruction.In this study,Vancomycin was used as a model drug.Halloysite clay nanotubes(HNTs)and poly(lactic-co-glycolic acid)(PLGA)were used to prepare HNTs-Van powder,PLGA-Van MPs,and pH-responsive porous PLGA-Van MPs,respectively.Their in vitro release characteristics and the effectiveness of medicated drugs against bacteria through the Kirby-Bauer assay illustrated that HNTs and PLGA can be used as a new generation of drug carrier material.This work about the fabrication of delivery system could support the experimental basis for the sustained-controlled-release drug delivery system of other drugs.In detail,this thesis mainly included the following issues: 1?The study of halloysite clay nanotubes(HNTs)as nanocarriers of vancomycinLaser particle analyzer,transmission electron microscopy(TEM)and so on were applied to character the properties of halloysite.The biocompatibility of halloysite was tested by MTT method.The characterization results suggested that HNT was tubular clays with different length,open ends and negative surface ?-potential.In addition,HNT exhibited good biocompatibility.The result indicates that HNTs can be utilized as an effective component in drug delivery systems.The preparation methods were investigated and confirmed that combine of sonication and vacuum was the best method for preparing HNTs-Van.The loading efficiency of Van in HNTs,entrapsulation efficiency and the cumulative release percent of HNTs-Van were 14.98%,8.83% and over 70%,respectively.The analysis of FTIR and TG indicated that Van was entrapped into HNTs.The effectiveness of medicated HNTs against S.aureus and B.streptococcus was through the Kirby-Bauer assay,indicating that the HNTs-Van exerted an effective antibacterial activity in the released period.2?The study of PLGA-Van MPsIn this section,PLGA-Van MPs were prepared with W/O/W double emulsion-solvent evaporation method with PLGA as the material for MPs.Several preparation factors of MPs,including the concentration of PLGA,the concentration of PVA,different drug-loading,the volume of internal aqueous phase,the stirring speed,the ultrasonic time using in the preparation of W/O emulsion,NaCl concentration in external aqueous phase,the viscosity of internal aqueous phase and the viscosity and average molecular weight(MW)of PLGA were investigated to optimize the best condition for the preparing of MPs.The results indicated that the resultant MPs were smmoth and the particle size distribution was approximately normally distributed with the particle size of 23 ?m.The loading efficiency of medicated MPs and entrapsulation efficiency were 6.14% and 51.85%,respectively.The cumulative release percent of Van MPs was 95% at 35 d.The effectiveness of medicated MPs against bacteria was investigated through the Kirby–Bauer assay.And the results indicated that the PLGA-Van MPs exerted an effective antibacterial activity in the released period.3?The study of pH-responsive porous MPsBased on the second section work,we used the similar method to prepare pH-responsive porous MPs using sodium chloride,sodium carbonate,sodium bicarbonate and ammonium bicarbonate as the candidate porogens,respectively.The morphology of MPs and particle size were studied using optical microscope.Entrapsulation efficiencies of different porogens were evaluated and compared.The results showed that the sodium bicarbonate was the best porogen for the fabrication of pH-responsive porous MPs.We investigated the effect of the concentration of porogen in the inner water on the properties of porous MPs by scanning electron microscope(SEM)and in vitro release characteristics.The porous resultant MPs increase the pore size of MPs with the increase of porogen in the inner waterphase.The resultant MPs showed the property of pH sensitive response.The cumulative release percent of PLGA-Van MPs was 95.81% in pH 5.0 while 33.18% in pH 7.4 at 50 d by in vitro release characteristics.In addition,the effectiveness of medicated MPs against bacteria was investigated through the Kirby–Bauer assay.The results indicated that the PLGA-Van MPs exerted antibacterial activity more effectively in pH 5.0 than in pH 7.4.The PLGA-Van MPs that developed herein can act as a pH-responsive controlled-release system at more acidic pH,minimizing the risk of toxicity to the healthy tissues and promoting the efficacy of the drug.