| Controlled drug-delivery system is a kind of drug-delivery procedure whichcould release drug slowly in a specific medium, because of its advantages such asreducing administration, improving patients compliance, reducing drug side effects onthe gastrointestinal tract, keeping stable and effective plasma concentration and so on,it has received more and more attention and importance. However, taking intoconsideration the complex environmental system of human body, there existsdifference between both the temperature and pH value of the normal tissue and lesionsite. So the intelligent drug release system being temperature and pH sensitive iswidely used in the study of drug carriers. Due to the obvious shortcomings of organicnano-materials such as poor chemical stability, low mechanical strength, imperfectcompatibility and low drug loadings, recently, with the development ofnano-technology, lots of inorganic nano-materials have become one of the mostimportant carrier materials having superior performance. Bimodal mesoporousmaterial (BMMs) as a new mesoporous material has been introduced, which consistsof worm-like mesopores of3nm as well as large inter-particles pores around10-30nm with the unique characteristics such as the controllable structure and particles size.BMMs with rich silicon hydroxyl can be carried out in surface modification throughphysical or chemical means to introduce the functional object and form mesoporousnanocomposites having environmental sensitivity.In this study, we synthetized the pH-responsible polymer Dex-PAA firstly, thenprepared the porous polymer-inorganic nanocomposites based on mesoporous BMMsand pH-sensitive polymer Dex-PAA. In addition the temperature sensitivenanocomposite NIPAAm-BMMs has been synthetized by one-step process. Finally,the pH and temperature responsive P (NIPAAm-AA) nanoparticle have been preparedvia copolymerizing of isopropyl acrylamide (NIPAAm) with acrylic (AA). Moreover,their characteristics such as assembly and release properties of drug areinvestigated．The main contents of our work are summarized as follows：1. The smart Dextran-Poly (acrylic acid) copolymers (D-A) have been preparedvia copolymerizing of acrylic acid (AA) with dextran. The effects of the molar ratio ofAA and dextran on pH-sensitivity of the obtained copolymers were investigated indetail. Meanwhile, ibuprofen (IBU) was applied as a model drug and the phosphatebuffer solution was chosen as the release medium to investigate the drug releaseperformance. The results showed that the sensibility of copolymer increases with theincreasing molar ratio of AA and dextran and loaded-ibuprofen could be rapidly and completely released in a controlled acidic medium as compared to that in alkalinemedium.2. The pH-sensitive poly (Dex-PAA) grafted to mesoporous surface ofamine-modified BMMs using two-step method, meanwhile, its structural features andperformances in a controlled drug delivery were systematically investigated withibuprofen as a model drug. The results demonstrated that the modification with NNgroups, loading drug and the addition of polymer D-A, all did not destroy the orderedmesoporous structure of BMMs. Moreover, by adjusting the grafted amount of D-A,the obtained composites (D-A/BMMs) were of a flexible control over drug loadingand release. The cumulative release yield of ibuprofen obtained from D-A/BMMs wasmuch higher at pH7.4than that at pH2.0, which suggested that the D-A/BMMsnanocomposite has an excellent performance of pH-responsive drug delivery.3. A facile grafting-onto strategy has been exploited to prepare a smarttemperature-controlled drug delivery system (NIPAAm-BMMs) via grafting isopropylacrylamide (NIPAAm) into BMMs. Furthermore, the temperature-responsivedrug-controlled delivery was systematically investigated by using ibuprofen as amodel drug. The studies have shown that the mesoporous ordered degree of BMMsand the drug loading capacity of NIPAAm-BMMs both were decreased with theincreasing amout of NIPAAm. Moreover, the cumulative release yield of ibuprofenfrom NIPAAm-BMMs were found much higher when the temperature was kept37℃,and among them all the sensibility was the best one, when mass ratio of NIPAAm andBMMs was1:1.4. The pH/temperature responsive nanoparticle P(NIPAAm-co-AA) was preparedby free radical precipitation polymerization method using NIPAAm and AA aspolymerization monomer. The results showed that the nanoparticle possessesnanosized spherical morphology and the particle size would be changed with thechanges in temperature and pH. The release properties of ibuprofen as a model drugwith P(NIPAAm-co-AA) were studied in detail, the results indicated that thecumulative release yield of ibuprofen was much higher in weak alkaline solution(93.3%) as compared to acidic solution (45.0%) when the temperature was kept same,furthermore, the cumulative release yield of ibuprofen was much higher at37℃(93.3%) than25℃(25.6%) under the same pH conditions, which further proved thatP(NIPAAm-co-AA) being sensitive to pH and temperature was expected to besuccessfully applied in drug controlled release.5. All the copolymers, mesoporous materials before and after modification, andrelated drug loaded samples were characterized by means of X-ray diffraction(XRD), scanning electron microscopy (SEM), transmission electron microscopy(TEM), N2adsorption-desorption, thermogravimetric analyses (TG), Particles/Zeta potential analysis,1H-NMR, Elemental analysis, Fourier transform-infraredspectroscopy (FT-IR), High performance liquid chromatography (HPLC) and UV-visspectra. |
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