Synthesis And Properties Of Anti-cancer/LDHs Nanohybrid

As we all know, most of anti-cancer drugs are toxic and have side effects. Theywill kill the cancer cells as while as helthy cells. So it is very important to develop anew kind of drug delivery system which is advantaged in bioavailability, biostability,reduced toxicity and high drug loading.Nowdays, layered double hydroxides (LDHs) have been reported as a newdelivery system. LDHs are a family of layered solids with structurally positivelycharged layers and interlayer balancing anions which can be replaces by the desiredanions. The drugs can be intercalated into LDHs to obtain drug/LDHs nanohybrids.The process of controlled release of drugs in governed both the electrostaticacctraction、hydrogen bonding and the stereo-hindrance effect, and this indicates thatthe nanohybrid can be used as a potential drug delivery system. In former researchswe found that it is more effective for anionic drugs than neutral or hydrophobic drugmoleculars to be intercalated into LDHs.In this paper, emodin has been successfully intercalated into Mg-Al-LDHs andMg-Zn-Al-LDHs with the method of re-assemble method. And we chose5-FU as theguest and Mg-Zn-Al-LDHs as the host material to synthesize5-FU/Mg-Zn-Al-LDHsnanocompounda via method of reconstruction. Powder X-ray diffraction SEM,FT-IR,TG and DTA were used to characterize the achieved products. Release mechanismand kenetics of emodin and5-FU from nanohybrids were investidated as well.The main contents of this paper are as follows:(1) Synthesis of emodin/LDHs with co-precipitation methodThe emodin/LDHs was prepared by coprecipitation method from mixed solutionof emodin, Magnesium and Aluminum chloride hexahydrates. The effect of differentratio of mixed solution, temperature and aging time were investigated. The resultsshow that the largest amount of drug loading is7%.(2) Synthesis and charaterisation of emodin/Mg-Al-SDS-LDHs①Emodin/Mg-Al-SDS-LDHs was synthesized by re-assemble method, and theeffect of temperature, aging time and the ratio of mixed solution wereinvestigated.The most effective uptake of emodin occurred in mixed solution(VC2H5OH：VH2O=1：2.5) media by Mg-Al-SDS-LDHs.The optimal conditions ofemodin/Mg-Al-SDS-LDHs were obtained:T=60℃, t=48h, pH=9.3, mass ratio40%. The maximum Ainvalue reached about22.48%under these conditions.②The XRD and FT-IR analysis indicated that the emodins were intercalatedinto the gallery of Mg-Al-SDS-LDHs. The determination results of the drug releaseindicated that the drug release rate from the emodin/LDHs nanohybrids was muchslower than that from the corresponding physical mixture at either pH=4.8or pH=7.5.The release mechanism was discussed：for the pH=7.5release, the mechanism isprimarily through ion-exchange with the ions in the buffer solution; while for thepH=4.8release, that is primarily through the dissolution of LDHs.The synthesis and characterization of emodin/Mg-Zn-Al-SDS-LDHs is same tothe emodin/Mg-Al-SDS-LDHs.(3) Synthesis and charaterisation of5-FU/Mg-Zn-Al-LDHs①The intercalation of5-FU into the interlayer of LDHs has been carried outusing reconstruction method to obtain5-FU/Mg-Zn-Al-LDHs nanohybrid.The effectof calcination time, calcination temperature were investigated. The results show thatThe maximum Ainvalue reached about30%(w/w)when calcination temperature ofprecursor is500℃for4hour, and the second step needs48h reconstruction under65℃.②The XRD and FT-IR analysis indicated that the5-FU was intercalated intothe gallery of Mg-Zn-Al-LDHs. The determination results of the drug releaseindicated that the drug release rate from the5-FU/Mg-Zn-Al-LDHs nanohybrids wasmuch slower than that from the corresponding physical mixture at either pH=4.8orpH=7.5. The release mechanism was discussed: for the pH=7.5release, themechanism is primarily through ion-exchange with the ions in the buffer solution;while for the pH=4.8release, that is primarily through the dissolution of LDHs.