Chitosan Hydrogel Induced Synthesis Of Nanomagnetite And Fabrication Of Concentric Layered Magnetic Hydrogel

Magnetite nanoparticle (MNP) is an important member of nano material field. MNP shows remarkable functional performances, including superparamagnetic, magnetic responsibility, magnetic induced heating as well as possibility of transport through the vascular system. These properties make MNP widely used in the field of drug target delivery system, hyperthermia, magnetic resonance imaging and purification. However, the synthesis of MNP and multifunctional MNP (such as water-soluble, high biocompatible and fluorescent) usually contains complex process and rigorous reaction conditions (such as high temperature, high pressure, inert atmosphere, organic solvent and organic surfactant). Hydrogel induced inorganic synthesis provides a new candidate for MNP, and hydrogel induced synthesis makes it possible for fabrication of organic-inorganic nano-composite with ordered structure. It is attractive to investigate the mechanism of chitosan hydrogel induced synthesis of MNP. Moreover, the studies of reaction-diffusion process in chitosan hydrogel would enrich the hydrogel induced synthesis theory.To address the above challenges, we proposed a facile way for synthesis of MNP using chitosan-iron ions complex (CS-Fe(II,III)) as precursor and chitosan hydrogel as reaction media. Concentric layered magnetic chitosan hydrogel (CL-MCS) has been fabricated based on reaction-diffusion process. XRD, SEM, ESEM, TEM, Raman spectrum, XPS and ICP were used to characterize the morphology of MNP and CL-MCS, and the mechanism has been discussed. The possibility of CS-MNP label MG-63 cells has been investigated, and magnetic controlled drug release from CL-MCS has been discussed.MNP have been synthesized induced by chitosan hydrogel via ion-assembly process and in-situ process at room temperature and normal atmosphere. Moreover, no organic solvent and surfactant was involved during synthesis. The chitosan in-situ-coated MNP (CS-MNP) with diameter of 10~30nm are superparamagnetic and have a 30wt.% chitosan coating. pH is an extremely important parameter during synthesis. Low pH induced CS-MNP with high crystallization and high saturated magnetization (Ms). The Ms of CS-MNP synthesis via ion-assembly process and in-situ process at pH=1.0 were 51.6emu/g and 55.5emu/g, which were 56% and 60% that of bulk magnetite. Moreover, CS-MNP with different morphologies, such as sphere, foursquare and rhombus, were obtained by varying pH during synthesis.The mechanism of chitosan induced synthesis of CS-MNP was proposed via the investigation of CS-Fe(II,III) formation and conversion, which enriched the hydrogel induced synthesis theory. Fe(III) and Fe(II) were chelated by amino and hydroxyl groups of chitosan hydrogel and CS-Fe(II,III) was formed. The Fe(III) and Fe(II) adsorption onto chitosan hydrogel was controlled by intraparticle diffusion process which followed Langmuir model of sorption. The sorbate concentration in equilibrium of Fe(III) and Fe(II) onto chitosan hydrogel were 68.6mg/g and 58.3mg/g, respectively. During CS-Fe(II,III) conversion to CS-MNP, chitosan hydrogel acted as reaction media and its amino and hydroxyl groups were in-situ coated on MNP, which induced CS-MNP with different morphology.Based on reaction-diffusion process in chitosan hydrogel, concenric layered chitosan hydrogel (CL-CS) and concentric layered magnetic chitosan hydrogel (CL-MCS) were manufactured via alternate alkali treatment. The layer number of CL-CS and CL-MCS N and alkali treatment time T followed rules below: N = 76. 8T0.71 and N = 79. 7T0.73. The quantitive rules of concentric layer position X n and the square root of reaction time t 1/2 and the position of the consecutive concentric layer coincide with the time law and space law of the classical Liesegang ring phenomena, respectively. However, the mechanism of CL-CS and CL-MCS fabrication was different from Liesegang ring phenomena. External electrolyte OH- reacted with inner electrolyte CS-NH3+ and CS-NH2 was obtained. CS-NH2 acts as a intermediate. Alternate alkali treatment resulted in periodical dispersion of COH- in chitosan hydrogel, which provided ordered variety for chitosan precipitation and formed CL-CS and CL-MCS.The cytotoxicity of CS-MNP, FITC-CS-MNP and AA-CS-MNP were investigated. No acute adverse effect was observed at doses up to 200mg/L and cell viabilities over 80% were obtained. Macropinocytosis is the main endocytic mechanism of MG-63 cells internalize nanoparticles, which might avoid lysosomal degradation of the nanoparticles. The nanoparticles were present in the form of agglomerates in MG-63 cells and distributed in cytosol, lysosome, vacuole and endoplasmic reticulum. The MCS and CL-MCS were loaded with Adriamycin (ADM) and Rafampicin (RFP), and magnetic controlled release of MCS and LC-MCS were investigated. A sustained-release effect had been expressed for both ADM and RFP, and the release profiles obeyed the diffusion-dissolution model. Magnetic stimulation can significantly enhance drug release from MCS, and the fraction release percentages of ADM and RFP have been improved by 31.9% and 39.3%, respectively. The concentric layered structure of CL-MCS improved the interface area between release medium and CL-MCS, which promoted drug release.