Preparation Of PH-responsive Polymers Coating Bimodal Mesoporous Materials And Its Application In Drug Delievery System

Since the discovery of M41s family in1992, the drug-sustained/controlleddelivery from mesoporous silica-based nanoparticles has received much attention dueto their interesting properties such as non-toxic nature, high surface area, large porevolume, tunable pore size and chemically modifiable surfaces. Recently, various typesof organic functional groups have been used as chemical switch to block moleculetransport from a silica-based mesopore and then to unlock the entrance for triggeredrelease under specific external stimuli. Therefore, in comparison with thesustained-release system, the stimuli-responsive drug delivery can improve thetherapeutic effectiveness and reduce the toxicity of drugs on normal tissue. Thus, it ishighly desirable to design a mesoporous silica-based composite material that canrelease the loaded drug in a specific environment by responding to external pH stimuli.However, taking into consideration of complex environmental system of human bodyand variations of pH in different parts, pH-sensitive drug delivery system becomesparticularly important.Bimodal mesoporous materials （BMMs） consist of worm-like mesopores of3nmas well as large inter-particles pores around10-30nm. Different from mesoporousmaterials with only monopore distribution, BMMs could realize the loading andsustained release of specific drug molecules through surface modification, especiallyfor the insoluble drugs, due to the unique characteristics such as the controllablestructure and particles size. In this thesis, the pH-responsible polymers （PMAA） weresynthesized by introducing the silane coupling agent. Meanwhile, the porouspolymer-inorganic nanocomposites based on BMMs and the prepared PMAA wereprepared. Furthermore, the properties of drug loading and release have beeninvestigated in detail. The main results of the research contents are summarized asfollows:1. The silanes-modified polymethylacrylic acid was prepared by free radicalpolymerization with different mass ratio of methacrylic acid （MAA） to vinytriethoxylsilane （VTES）. The swelling dynamics of the prepared polymers wereinvestigated in detail. The results showed that the swelling behaviors varied with thecontents of methacrylic acid （MAA） in the polymers, and the swelling ratio increasedwith the increase of pH value of the solution. The swelling properties of prepared polymers in NaC1and CaCl₂solutions with different pH values and concentrationswere also investigated. The demonstration showed that the influences of the ionicstrength and the charge of positive ions in the solution were obvious. When the pH ofthe solution was alternated between1.4and9.0, the polymers exhibited rapidreversible swelling-deswelling property and responsive rates.2. A facile grafting-onto strategy have been explored to prepare a smartpH-controlled drug delivery system （P-B） via surface-grafting of the preformedsilane-modified PMAA onto the mesoporous surface of BMMs in which the PMAAacted as the pH-sensitive component and the preformed silane provided an anchoringsites with the surface-OH group of BMMs. The results showed that the orderedmesoporous structures were not destroyed after introducing of polymer PMAA intothe surface of BMMs, but their specific surface and pore volume afterpolymerization decreased significantly. The effects of additive amount of theloaded-PMAA on the structure properties of nanocomposites was significant,however, when the content of polymer PMAA was about50%, the nanocompositesstill held a relatively large pore volume （1.23cm³/g） and high surface area （928.83m²/g）.3. Ibuprofen （IBU） was employed as a model drug and the phosphate buffersolution was chosen as the release medium to investigate the drug deliveryperformance. The results showed that after the loading of ibuprofen the specificsurface area, pore size and pore volume of the IBU-loaded nanocomposites weredecreased, suggesting the successful encapsulation of IBU. Meanwhile, the obtainednanocomposites showed a flexible control over drug release by adjusting the graftedamount of PMAA and the IBU-loaded amount decreased with the increasing ofPMAA content in composite materials. In a test of in vitro drug release, the drugrelease amount of the IBU-loaded nanocomposites was pH-dependent and increasedwith the increasing of pH value, implying that the drug loaded nanocomposites arepromising drug-carriers to construct pH-responsive controlled drug delivery systems.When the content of polymer PMAA was about50%, the pH sensitive performancewas the most significantly in the nanocomposites. These pH-sensitive mesoporousnanocomposites are expected to have potential applications of drug absorption andrelease delivery. 4. X-ray diffraction, scanning electron microscopy, transmission electronmicroscopy, N₂adsorption-desorption, thermogravimetric analyses, Fouriertransform-infrared spectroscopy and UV-vis spectra were employed to evaluatestructural characteristics and textural properties of mentioned-above materials. Therelated loading and pH-dependent release mechanism were proposed.