| To address the limitations and disadvantages of traditional systemic drug delivery,drug-releasing implants(DRI)based on the generation of nanoengineered surfaces on existing medical implants have attracted great attention.TNTs prepared by anodizing metallic titanium(Ti)in an electrolyte are recognized as one of the most outstanding drug-releasing implants in drug delivery systems because of their excellent properties with controllable nanotuben diameters,highly ordered hollow nano-structures,tailorable surface chemistry.However,titania nanotube arrays present limitations in the drug release characteristics with a rapid drug release at the initial stage of release which may have a negative effect on the bone environment.As an orthopedic implants drug delivery system,long-term sustained release can significantly reduce the noxious side-effects and improve the therapeutic effect of the drug loaded on TNTs.Bone infections are the most common clinical complications associated with bone implants.This is a serious adverse condition in orthopedics,which requires release of drugs on-demand.In this study,through a electrochemical anodization method,TiO2 nanotube arrays on the titanium surface were built as drug carriers.Then,modify the surface chemistry of the nanotubes by using several different surface modification methods to achieve an extended drug release from TNTs.Firstly,a novel implantable local drug delivery system was successfully fabricated by decorating TNTs with mesoporous silica nanoparticles(MSN)and loaded with alendronate sodium(ALD)as a model of a water-soluble drug to explore the drug load,release and release kinetics of the carriers.MSN decorated on TiO2 nanotube by the hydrothermal treatment led to improve the loading effect of drug and prolonged drug release.Furthermore,the surface modification of TNTs with MSN was found to increase the biocompatibility and the TNTs-MSN composites hold good stability.Secondly,to further enhance the interaction between the surface of TNTs-MSN composites and the drugs.APTES(3-Aminopropyltriethoxysilane)was grafted on the surface of TiO2 nanotube arrays and TNTs-MSN composites before loading alendronate sodium.The APTES grafting on the sampes improve the bind between the sampes surface and the drug by electrostatic attraction with alendronate sodium,which can enhance the drug adsorption capacity of the sampes and improve extend drug release.The interactions between the sampes surface and APTES was that the silane groups react with Si-OH presented on the sampes surface to form a silanized surface and free terminal-NH2 groups,which away from the sampes surface.Thirdly,to ameliorate nonspecific toxicities and enhance the therapeutic efficacy,MSN was decorated on TNTs through the hydrothermal.Then by vacuum drying method,ibuprofen were loaded into the TNTs-MSN composites,by a simple immersion method,chitosan coating was deposited on the surface of titania nanotube arrays.The pH-responsive drug delivery system that can release drugs under pH of the inflammatory and tumor cells(pH 6.8)more easily than pH of normal tissues(pH 7.4).It can provide a promising control-release manner to achieve a good therapeutic effect for localized drug delivery.At last,decorating TNTs with mesoporous hydroxyapatite nanoparticles(m-HAp)and loaded with alendronate sodium to further enhance the interaction between the surface of TNTs-HAP composites and the drug and explore the drug load,release and release kinetics of the carriers.M-HAP decorated on TiO2 nanotube by the hydrothermal treatment led to improve the loading effect of drug and extend drug release,increase the biocompatibility. |
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