Synthesis Of Large-Sized Drug-LDH Nanohybrids And Their In Vitro Release And Thermal Decomposition Properties

Recently, layered double hydroxides (LDH), as a kind of anion clays, have exhibited extensive research interest in the area of drug controlled/sustained release system, due to their low cytotoxicity and high biocompatibility. In our study, a series of large-sized drug-LDH nanohybrids with different particle size were synthesized by hydrothermal treatment. Their crystal structures, compositions, morphology, in vitro release behavior and mechanism and thermal properties were detailed studied by using XRD, FT-IR, ICP, TG-DTA, SEM, TEM/HRTEM, UV-Vis, in situ XRD and in situ FT-IR analyses.A series of large-sized drug-LDH nanohybrids have been prepared by using hydrothermal method without any organic solvent. (1) Hydrothermal treatment has significant positive effects on the improvement of particle size and crystalline, comparing to traditional corprecipitation treatment. (2) Large-sized ibuprofen (IBU) intercalated MgAl-LDH (MA-IBU-LDH) between the range of 150-700 nm are synthesized by varying aging temperature and aging time. The particle sizes of MA-IBU-LDH are improved gradually with the increasing of aging time and the best hydrothermal temperature for their crystalline is 150℃. (3) Large-sized IBU intercalated ZnAl-LDH (ZA-IBU-LDH) (320-430 nm) and naproxen (NAP) intercalated MgAl-LDH (MA-NAP-LDH) (190-330 nm) are obtained by varying aging time at 150℃and 130℃, respectively. The best aging time for the crystalline of ZA-IBU-LDH is 36 h.The in vitro release test of MA-IBU-LDH and ZA-IBU-LDH with different particle size in pH=7.45 PBS are systematically studied, respectively. (1) It can be found that the particle size plays an important role on release rate. (2) The kinetic simulation to the release profiles suggests that the release processes of the larger MA-IBU-LDH nanohybrids (>400 nm) are mainly controlled by intraparticle diffusion, but surface diffusion and heterogenous particle diffusion upon ion-exchange process to larger ZA-IBU-LDH nanohybrids (>300 nm), due to their difference of the aggregation and adhesion states and the morphology changes during the release process. (3) By quasi-in-time monitoring the morphology and structure changes of the large-sized MA-IBU-LDH during the release process, one can find that the main reason leading to margin-curving LDH particles is the hydrophobic aggregation mechanism of the interlayer exchanged hydrophobic IBU anions, and the large-sized margin-curved phosphate-intercalated LDH particles (>300 nm) are obtained for the first time. Based on the analyses of the samples recovered at different release time, a release mechanism model of the as-prepared IBU-LDH nanohybrids is tentatively proposed along with their morphology changes during the whole release process.The thermal decomposition properties of large-sized drug-LDH are determined systematically. (1) The thermal stabilities of drug molecules are obviously improved after intercalated into LDH interlayers, compared to pure ones. (2) The thermal decomposition process of large-sized MA-IBU-LDH nanohybrids is divided into five steps, including the loss of interlayer water, dehydroxylation of the LDH layer, and the decomposition of carboxyl, carbon chains and phenyl ring of IBU molecule. Based on the analyses of in situ XRD, in situ FT-IR and TG-MS, a thermal decomposition model of large-sized MA-IBU-LDH is tentatively proposed with the structure transformation at different temperature stages.