Co-synthesis and drug delivery properties of mesoporous hydroxyapatite-silica composites.

In this work, mesoporous hydroxyapatite-silica (HA-silica) composite materials with four different Si:Ca:P ratios were sol-gel derived through self-assembly using triblock copolymer Pluronics P123 as template. The composition and mesoporous structure formed were characterized by X-ray diffraction and electron microscopy. The XRD patterns indicated that the intensity of the HA phase becomes stronger as the Ca/Si ratio of the composite increases. From nitrogen gas analysis at 77 K, type IV isotherm plots for typical mesoporous materials were observed for all of the samples. However, the mesoporous structure of HA-silica tends to becomes less ordered as the Ca/Si ratio increases. Promising consistency between the pore sizes from the Barrett, Joyner and Halenda (BJH) method, Transmission Electron Microscopy (TEM) and Small Angle X-ray diffraction (SAXRD) was also observed. The formation mechanism of mesoporous HA-silica composites was proposed, where the interaction between the crystallization of HA and the surfactant liquid crystal determines the regularity of the meso-structure. In vitro drug loading and release studies showed that drug loading capacity is dependent on the pore volume of the sample, and the mesoporosity of the samples were responsible for the sustained release of drugs. In vitro cell culture of the samples showed promising biocompatibility where osteosarcoma cells were observed to grow favourably on the synthesized composites.

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin.

The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as ß-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.

Biomedical applications of hydroxyapatite nanoparticles.

Nanotechnologies have the potential to improve current disease diagnosis due to their ability to circulate in the blood and distribute in the body to image tissues and cells or therapeutical applications to deliver a payload. Among nanoparticles with different materials composition, inorganic nanoparticles composed of calcium phosphate have numerous advantages including ease of synthesis, control of physico-chemical properties, strong interactions with their payload, and biocompatibility. In this review we discuss the different routes of synthesis of calcium phosphate nanoparticles, novel systems, strategies to load agents, biostability and cytotoxicity, biodistribution and pharmacokinetics, bio-imaging and therapeutical applications.

In situ SAXRD study of sol-gel induced well-ordered mesoporous bioglasses for drug delivery.

In this work, two systems of mesoporous bioglasses (MBGs) were sol-gel derived using block copolymer pluronic F127 and P123, respectively, as templates. A two-dimensional hexagonal (P6mm) mesoporous structure was obtained for the two systems, with d-spacing in (100) reflection of 8.49 nm for P123-templated MBG (P123-MBG) and 10.26 nm for F127-templated MBG (F127-MBG). The phase transformation behavior for the systems was elucidated using an in situ synchrotron small angle X-ray diffraction approach, with the corresponding mechanisms proposed. It was indicated that both systems go through a complicated phase transformation, from a disordered to a finely ordered hexagonal structure during the self-evaporation process. The surfactants not only acted as templates for the ordered structure, but also enhanced the rigidity of Si-O network, which prevented disruption to the ordered Si-O arrangement by the Ca(2+) and P-O group. In vitro bioactivity study showed similar bioactivity for both the P123-MBG and F127-MBG systems. Drug loading and release studies using a model metoclopramide drug showed that both MBGs presented better loading and release compared to normal bioglass (BG). The significantly higher loading and better sustained release for P123-MBG, compared to F127-MBG, is attributed to its higher pore volume and surface area.