Vesicles Formation Induced By LDHs And The Composites Of (Drug-LDHs)@Vesicles

Layered double hydroxides (LDHs), also known as anionic clays or hydrotalcite-like compounds (HTlc), are a class of layered inorganic materials that consist of structurally positively charged layers and exchangeable anions in the interlayer gallery for charge balance. LDHs have widespread applications in many fields such as anion adsorbents, catalyst supports, catalysts and membranes. More recently, LDHs are attracting much more attention in drug delivery and gene therapy thanks to their biocompatibility, anion-exchange property and nontoxicity. The drugs can be intercalated into LDHs to obtained drug-LDHs nanohybrids. As the process of controlled-release of drugs is governed by the host-guest interaction involving electrostatic attraction, hydrogen bonding and the guest-guest interaction within the two-dimensional interlayer gallery, the nanohybrids could be used as a potential drug delivery system.Vesicles are one kind of organized aggregates of amphiphilic molecules, which have closed bilayer shells that encapsulate an aqueous interior. They exhibit a rich structural behavior and are of interest both fundamentally and practically. Vesicles are able to encapsulate active molecules and therefore can be used in drug delivery systems.So far by now, the methods of vesicle preparation have been widely studied, including mechanical force method and self-assembly method. In fact, the latter is becoming more and more popular. Hanczyc et al. reported that clay minerals can catalyze the formation of vesicles from fatty acids; in turn, the clay minerals and any other molecules on their surface often become trapped in these vesicles. We have reported a structurally positively charged synthetic clay, layered double hydroxides (LDHs) induced the vesicle formation in a mixture of a zwitterionic surfactant (dodecyl betaine) and a double chained anionic surfactant (Aerosol OT (AOT)). Moreover, parts of LDHs particles were encapsulated in vesicles to form composites. As far as we know, these studies on the LDHs-mediated vesicles formation have not been reported by any other researchers. No direct evidence has yet been put forward to clarify the concerned mechanism of the vesicles formation induced by LDHs, as well as the characteristics qualities of the composite of LDHs encapsulated in vesicles (named LDHs@vesicles). In order to test the generality of this phenomenon and to shed light on the mechanism of LDHs-induced vesicle formation, in this study we investigated the spontaneous formation of vesicles induced by LDHs in an aqueous catanionic surfactant solution composed of sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) and a zwitterionic/anionic surfactant solution composed of lauryl sulfonate betaine (LSB) and sodium dodecyl benzenesulfonate (SDBS). The mechanism of LDHs induced vesicle formation was explored.New drug delivery system was one of the important researches in drug dosage forms study. Since both vesicles and LDHs could be used in controlled drug molecules release, the composites of LDHs@vesicles are expected to be used as a new drug delivery system potentially. Therefore, in this paper we did preliminary investigation on the composites of LDHs@vesicles. First, with LDHs chosen as host material and anticancer drugs as guest species, Ifosfamide (IFO) and Camptothecin (CPT) have been successfully intercalated into LDHs to obtain IFO-LDHs and CPT-LDHs nanohybrids. In the last section, these two nanohybrids IFO-LDHs and CPT-LDHs were introduced into the forementioned two surfactant solutions in order to induce vesicles formation and finally get the composites of (IFO-LDHs)@vecicles and (CPT-LDHs)@vesicles. The properties of obtained composites, released behavior of composites were systematically studied. Contrast experiments were employed to study the difference between the drug-LDHs nanohybrids and the composites of nanohybrids@vesicles.The main contents of this paper are as follows:(1) Positively charged Mg3Al layered double hydroxides (LDHs) nanoparticles can induce the spontaneous formation of vesicles in a catanionic micelle solution of sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) and in a zwitterionic/anionic micelle solution composited of lauryl sulfonate betaine (LSB) and sodium dodecyl benzenesulfonate (SDBS). Composites of LDHs nanoparticles encapsulated in vesicles (LDHs@vesicles) were formed. The size of composites increased with the increase of concentration of Mg3Al-LDHs nanoparticles.(2) A possible mechanism of LDHs-induced vesicles formation was suggested. The positive charged LDHs surface attracts negatively charged micelles or free amphiphilic molecules, which facilitates their aggregation into bilayer patches. The bilayer patches connect to each other and finally close to form vesicles. If the patches curve toward the LDHs particles, the composites of LDHs@vesicles were formed. It was also found that adsorbed compound micelles layers on the LDHs surface played a key role in the vesicle formation.(3) With LDHs chosen as host material and anticancer drugs as guest species, Ifosfamide (IFO) and Camptothecin (CPT) have been successfully intercalated into LDHs using assemblage and coprecipitation methods to obtain IFO-LDHs and CPT-LDHs nanohybrids. The properties of obtained nanohybrids, released behavior of nanohybrids were systematically studied. The in vitro drug release from the nanohybrids is remarkably lower than that from the corresponding physical mixture at pH 7.5. The release mechanism of drug molecules from the nanohybrids obeyed Bhaskar model. The diffusion process of the drugs in the interstices and interlayers of nanohybrids is the rate-limiting step.(4) Drug-LDHs nanohybrids can induce vesicles formation both in SDS/DTAB and SDBS/LSB micelles solution and finally the composites of (drug-LDHs)@vesicles were formed.(5) The release behavior of CPT from the composites of (CPT-LDHs)@vesicles in buffer solution (pH 7.5) was investigated using dialysis bag method. Compared with CPT-LDHs nanohybrids, the in vitro drug release behavior was better than CPT-LDHs. The CPT molecules released through the membranes of vesicles after first releasing from the nanohybrid. The release kinetics of CPT from the nanohybrid obeyed Bhaskar model. The diffusion process of CPT in the interlayers of nanohybrid and vesicles was the rate-limiting step. The results show that the composites of (drug-LDHs)@vesicles are potential drug controlled release system.(6) The dispersibility of (drug-LDHs)@vesicles was obviously better than the nanohybrids. This may provide an important method to resolve the problem of the bad dispersibility of drug-LDHs nanohybrids.