Fabrication Of Drug (Ibuprofen And Folic Acid)-LDH Hybrids Via A Delamination-Reassembling Method

Layered double hydroxides (LDHs) are a class of layered inorganic materials. Recently, LDHs are attracting much more attention as a new drug delivery system, and widely research has been made to the preparation and property of drug-LDH nanohybrids. Conventional methods to synthesize IBU-LDH nanohybrids including: ion exchange, co-precipitation, reconstruction and hydro thermal methods. However, these conventional methods have the following drawbacks:complex processes, time-consuming, low drug loading amount and high reaction temperature, expecially water-insoluble drug molecules and large size molecules could not intercalated effectively. It is a challenge to overcome the drawbacks of conventional methods and prepare drug-LDHs nanohybrids with high drug loading.Rencently, delamination/reassembling process became a comparatively new focus of study for LDHs. Under certain conditions, LDHs nanoparticles can be delaminatated into nano sheets, and it could assemble with organic to systhesis organic-LDH nanohybrids. Delamination/reassembling process had been successful applied to systhesis organic-LDH untrathin film and macromolecule-LDH nanohybrids.To date, to the best of our knowledge, the synthesis of drug-LDH nanohybrids by the delamination/reassembling process has not been reported. Exploring the feasibility and characteristics of delamination/reassembling process to prepare drug-LDH nanohybrids has great importance for the targeted drug delivery-controlled release formulation.Main contents and conclusions:(1) We chose non-steroidal anti-inflammatory drug ibuprofen as the guest molecule and Mg3A1LDH as the host material to synthesize IBU-LDH nanohybrid via delamination/reassembling process. The achieved products were characterized. The impact of prepare condition for drug loading were researched., and the release mechanism and kinetics of drug from nanohybrids were investigated as well. The IBU molecules arrange as a slightly tilted bilayer with the long axis perpendicular to the brucite-like layer. Compared with the conventional methods, the delamination/reassembling process exhibits excellent characteristics, such as simple procedure, short reaction time, mild condition and high drug loading. The drug loading of nanohybrids could be controlled by the change of mass ratio of IBU/LDH nanosheets. The release rate of IBU from the nanohybrid was lower than that from the physical mixture. It was found that the pseudo-second-order model and Bhaskar equation were better satisfactory for describing the release kinetic process of IBU from the IBU-LDH nanohybrid. The diffusion through the particle was the rate limiting step.(2) We chose folic acid as the guest molecule and Mg3A1LDH as the host material to synthesize FA-LDH nanohybrid via delamination/reassembling process, and the achieved products were characterized. The impact of preparation condition for the drug loading is investigated. The possible orientation of FA molecules in the LDH gallery is proposed. The results show that, compared with the conventional methods, the delamination/reassembling process exhibits excellent advantages. The drug loading of nanohybrids could be controlled by the change of mass ratio of IBU/LDH nanosheets. According to the gallery height of FA-LDH nanohybrid and the size of FA molecules, the folic acid molecules were arranged in tilted monolayer with tilting angles of about60℃. These results offered references for the targeted delivery system based on LDH.(3) In order to study the application of drug-LDH nanohybrids in oral drug delivery systems, we chose IBU-LDH nanohybrid as matrix, SAA and CS as coated means, Ca2+as crosslinking media. Thus we prepared three different kinds of beads which were named (IBU-LDH)@CaAA、(IBU-LDH)@(CaAA+CS) and (IBU-LDH)@CaAA@CS. The swelling and the release behavior of the beads were investigated in pH2.1and7.4. The results indicated that, the swelling ratio of the beads in pH2.1PBS was minimal and thus the drug release was also minimal. However, the beads swollen obviously in pH7.4PBS, and the release rate was increased significately. It was found the swelling and the releasing of IBU was affected by the pH. The results suggested that the alginate beads would be a good candidate for the oral drug delivery system.