New Inorganic-Based Drug Delivery System of Indole-3-Acetic Acid-Layered Metal Hydroxide Nanohybrids with Controlled Release Rate

Abstract

We have developed new inorganic-based drug delivery systems through the hybridization of indole-3-acetic acid (IAA) and layered metal hydroxide such as zinc basic hydroxide salt (ZBS) and zinc aluminum layered double hydroxide (ZALDH). A coprecipitation method as well as an ion-exchange route is found to be commonly effective in synthesizing both IAA-ZBS and IAA-ZALDH nanohybrids, in which the tilted bilayers of IAA are stabilized in the interlayer space of layered metal hydroxide lattice. According to the FT-IR spectroscopic analyses, IAA molecules interact more strongly with the ZBS lattice than the ZALDH one, which is due to the formation of coordination bonds between carboxyl groups of the guest species and coordinatively unsaturated Zn(OH) 3 units of the host ZBS lattice. Such an interaction gives rise to a slower release of the IAA molecules from the ZBS-based nanohybrid than from the ZALDHbased one. The present results underscore that the layered hydroxydouble salt like ZBS makes it possible to design and develop new efficient drug-delivery systems with the suspended release of guest molecules. IntroductionRecently, intense research interests have paid on layered inorganic solids because of their ability to encapsulate and immobilize various bio-and organic molecules in the interlayer space. 1-5 In particular, layered double hydroxide (LDH) with brucite-type lattice can act as a gene reservoir and/or a drug-delivery system (DDS). 3,4,6-11 The positive surface charge of LDH layer caused by the partial substitution of divalent cations with trivalent ones makes it possible to intercalate negatively charged drug-or biomolecules like DNA. For the practical use of LDH as a drug delivery vector, it is very important to control the release rate of drug molecules, 11 because it determines the retention time of drug molecules in vivo. Such a regulation of the disintercalation kinetics of intercalated organic molecules can be achieved by tuning the chemical interaction between host and guest. It has been well-known that metal vacancy in the brucitelike layer leads to the phase transformation into hydroxydouble salt (HDS) such as Zn 5 OH 8 (NO 3 ) 2 ‚2H 2 O, in which coordinatively unsaturated Zn(OH) 3 units are formed up and down side of vacant octahedral sites of brucite-like layers, and exposed to the interlayer space of the HDS lattice. Like the LDH phase, there are exchangeable interlayer anionic species in the HDS lattice to neutralize the positive charge of host layer and hence this material has an ability to form the intercalation complexes with negatively charged organic molecules. [12][13][14][15] The presence of the coordinatively unsaturated Zn(OH) 3 units directed to interlayer space allows the HDS phase to strongly interact with guest molecules. In this regard, it is highly feasible that the intercalation of drug molecules into the HDS phase would produce new inorganicbased DDS with slow release kinetics of guest drug molecules. Moreover, the HDS phase has an additional advantage over the LDH phase such ...

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