Preparation And Property Of Surface Modified Drug-LDH Nanohybrids

Layered double hydroxides (LDHs) are a class of layered inorganic materials. More recently, LDHs are attracting much more attention thanks to potential application in drug delivery. The drugs can be intercalated into LDHs to obtained drug-LDH nanohybrids. Because of the host-guest interaction and the guest-guest interaction within the two-dimensional interlayer gallery, drug-LDH nanohybrids could controll-release drugs as potential drug delivery and controlled-release system. The LDHs have many advantages, such as good biocompatibility, nontoxicity and biodegradability. However, there are still some problems. The drug-LDH nanohybrids lack in disguising and targeting abilities and exhibit weak water re-dispersibility. These problems should be resolved before clinical trials and applications. Surface modification of drug-LDH nanohybrids is an effective method to solve them. Polyethylene glycol (PEG) and Folic acid (FA) have been widely used in the modification of drugs and drug carriers. The former endows system with disguise function and good water redispersibility; the latter endows system with targeted function. Liposomes have attracted much attention for their potential application in drug delivery. Liposomes are formed in water by the self-assembly of lipid molecules, which yields a lipid bilayer shell surrounding an aqueous core. We think that using liposomes wrap the drug-LDH nanohybrids up to obtain (drug-LDH)@liposome composites. The composite can improve water re-dispersibility and drug-release efficiency of drug-LDH nanohybrids. Liposomes have good biocompatibility and targeted function, so (drug-LDH)@liposome composites have potential application in drug delivery and controlled-release system. The preparation and drug-release efficiency of drug-LDH nanohybrids has been widely investigated, but there is less report on the study of modification of drug-LDH nanohybrids.In this paper, drug-LDH nanohybrids are modified by chemical bonding and liposome encapsulating methods using diclofenac sodium (DICS) as model drug and using PEG, FA and egg yolk lecithin as model modifiers. The properties, such as water re-dispersibility and drug released behavior were systematically studied. It can provide basic data to the research of drug delivery and controlled-release system.The main contents of this paper are as follows:(1) Using (3-aminopropyl) trimethoxy silane (APTMS) as linker agent, the Mg3Al-NO3LDH particles were surface modified by PEG with disguise function and FA with targeted function. The surface modified LDH particles exhibit good water re-dispersibility which is mainly attributed to the space steric effect of the modified layers. Surface modification of LDH particles can be controlled by the variation of the amount of PEG and FA used in raw materials.(2) DIC-LDH nanohybrids were prepared by coprecipitation method and then surface modified by PEG and FA. The results show that surface modified DIC-LDH particles exhibit good dispersibility, water re-dispersibility and drug-release efficiency. The DIC molecules released through the modified layer after first releasing from the nanohybrid.(3) DIC-LDH nanohybrids were prepared by delamination-restacking method and then praperaion of (DIC-LDH)@liposome by the reverse-phase evaporation method. The (DIC-LDH)@liposome has good stability and re-dispersibility. It can not only resolve the problem of liposome’s instability, but also overcome the shortcoming of DIC-LDH. The in vitro drug release behavior of surface modified DIC-LDH was better than DIC-LDH nanohybrids.