| Mesoporous silica nanoparticle(MSNs) have shown great potential in controlled drug delivery system owing to their large surface areas and pore volumes, tunable pore size, unique mesoporous structure, convenient modification and good biocompatibilities. Bimodal mesoporous material(BMMs) as a new mesoporous material has been introduced, which consists of worm-like mesopores of 3 nm as well as large inter-particles pores around 10-30 nm. The unique structure of the carrier has a significant influence for drug-loading and controlled drug release performance. The human body is a complex environmental system, and exhibits variations in pH between the normal tissue and lesion site. However, BMMs are not sensitive to stimuli and show no controlled release performance, which limits their application in drug-delivery systems. Various studies concerning the application of pH-responsive polymer as novel drug delivery systems have been actively pursued due to their pH-sensitive performance by changing the pH in recent years. The polymer-coated silica hybrid nanocomposite can not only possess high drug loading content but release drugs at the site of action in response to external or internal stimuli efficiently. Based on the research background as above, the pH-responsive polymer PMAA were synthetized firstly then the polymer-inorganic nanocomposites were prepared based on mesoporous silica BMMs. Moreover, their characteristics such as assembly and release properties of ibuprofen(IBU) were investigated.The main contents of our work are summarized as follows:1. PMAA was incorporated when amino-modified NN-BMMs applied as carriers were loaded with ibuprofen(IBU). The resulting products were marked as P/I-NN-BMMs-x(x is 0, 0.1, 0.3, 0.5, 1.0), in which x is the mass ratio of PMAA and NN-BMMs. The drug-loading performance of the obtained products and the effect of the introduction of PMAA on the structure of the products were investigated in detail. Meanwhile, the phosphate buffer solutions with different pH values were chosen as the release medium to investigate the drug release performance of the relevant samples. The results demonstrated that the modification with NN groups, loading drug and the encapsulation of PMAA, all did not destroy the ordered mesoporous structure of BMMs. Meanwhile, the trend of the grafted-PMAA amount increased first and then decreased with the increasing mass ratio of PMAA. The grafted-PMAA amount of P/I-NN-BMMs-0.5 was more(about 6.2%);The loaded-ibuprofen showed higher release yield in a controlled acidic medium as compared to that in alkaline medium. P/I-NN-BMMs-0.5 showed the better sensibility.2. pH-dependent [poly(methacrylic acid)]-silica hybrid nanoparticles P/NN-BMMs-x(x is 0, 0.1, 0.3, 0.5), in which x is the mass ratio of PMAA and NN-BMMs were prepared by coating poly(methacrylic acid)(PMAA) onto amino-modified surface of BMMs via the “graft to” strategy. Meanwhile, the influences of the encapsulated amount of PMAA and synthesis parameters on the structural and textural properties of resultant hybrid materials were investigated. Ibuprofen(IBU) was selected as a model drug, and the drug-loading kinetics of the obtained composite nanoparticles were preliminary evaluated. The results demonstrated that the mesoporous structures could be maintained after the modification with NN groups and the addition of PMAA. The amount of the encapsulated PMAA was more due to more active site existed on NN-BMMs and the grafted-PMAA amount of P/NN-BMMs-0.5 was the most(about 21.8%). Moreover, loading rate constant(k) values for P/NN-BMMs-0.1, P/NN-BMMs-0.3 and P/NN-BMMs-0.5 are 0.58, 0.42 and 0.39, indicating that the drug-loading rate decreased remarkably with the increase of the amount of the PMAA grafted onto the surface of BMMs. particularly, their drug-loading kinetics fits Korsmeyer-Peppas model.3. Ibuprofen(IBU) was encapsulated into pH-sensitive hybrid nanocomposite using amine-modified bimodal mesopores silica as core and poly(methylacrylic acid) as shell. Meanwhile, the structure features of obtained IBU-loaded nanocomposites P/I-NN-BMMs were characterized indetail. On the other hand, the drug loading and release performance of the IBU-loaded nanocomposites was investigated. In addition, in order to elucidate their pH responsibility in various pH and ionic strength solution, measurement of its zeta potential at various pH values and ionic strength solution was pursued. The results showed that mesoporous structures of the nanocomposites could be maintained. What’s more, the nanocomposites possessed high drug loading capacity and the IBU loading capacities were 22.61% for P/NN-BMMs-0-I, 17.57 % for P/NN-BMMs-0.1-I, 13.60 % for P/NN-BMMs-0.3-I and 13.30 % for P/NN-BMMs-0.5-I, suggesting that the loading capacities decreased with the increasing graft amount of PMAA. Zeta potential profiles of prepared PMAA indicated that the increase of pH values in solution led to an increase amount of-COOexisted in PMAA chains and the NaCl with various ionic concentrations dissolved in ammonia solutions could screen the electrostatic charges of the PMAA molecules. So the polymer PMAA was responsive to various pH and ionic strength. The sensibility of the nanocomposites increased with the increasing graft amount of PMAA. In particularly, the burst behaviors in an initial releasing stage disappeared with a controllably sustained performance. Finally, the release profiles indicated a “diffusion-controlled” release mechanism in acidic medium. In alkaline medium, the release profiles were controlled by “diffusion-controlled” release mechanism at first and then concentration gradient.4. PMAA, mesoporous materials before and after modification and related drug loaded samples were characterized by means of X-ray diffraction(XRD), scanning electron microscopy(SEM), transmission electron microscopy(TEM), N2 adsorption-desorption, thermogravimetric analyses(TG), zeta potential analysis, elemental analysis, fourier transform-infrared spectroscopy(FT-IR), high performance liquid chromatography(HPLC) and UV-vis spectra. |
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