Surface-functionalized layered double hydroxide nanocontainers as bile acid sequestrants for lowering hyperlipidemia.

The surface modification of two-dimensional (2D) nanocontainers with versatile chemical functionalities offers enormous advantages in medicine owing to their altered physicochemical properties. In this study, we demonstrate the fabrication of surface-functionalized layered double hydroxides (LDHs) towards their use as effective intestinal bile acid sequestrants. To demonstrate these aspects, the LDHs are initially modified with an amino silane, N1-(3-trimethoxysilylpropyl) diethylenetriamine (LDHs-N3),which, on the one hand, subsequently used for the fabrication of the dendrimer by repetitive immobilization of ethylene diamine using methyl acrylate as a spacer. On the other hand, these surface-functionalized LDHs are wrapped with an anionic enteric co-polymer to not only prevent the degradation but also increase the stability of these 2D nanoplates in an acidic environment of the stomach to explore the in vivo efficacy. In vitro cholic acid adsorption results showed that these surface-functionalized LDHs displayed tremendous adsorption ability of bile salt. Consequently, the bile salt adsorption results in vivo in mice confirmed that the enteric polymer-coated diethylenetriamine silane-modified LDHs, resulting in the reduced cholesterol by 8.2% in the high fat diet-fed mice compared to that of the oil treatment group with augmented 28% of cholesterol, which gained weight by 6.7% in 4 weeks. Notably, the relative organ (liver and kidney) weight analysis and the tissue section of histology results indicated that the modified LDHs showed high biocompatibility in vivo. Together, our findings validate that these surface-functionalized 2D nanoplates have great potential as effective intestinal bile acid sequestrants.

Comparison of segmental spinal movement control in adolescents with and without idiopathic scoliosis using modified pressure biofeedback unit.

BACKGROUND: Postural rehabilitation emphasizing on motor control training of segmental spinal movements has been proposed to effectively reduce the scoliotic spinal deformities in adolescent idiopathic scoliosis (AIS). However, information regarding the impairments of segmental spinal movement control involving segmental spinal stabilizers in adolescent idiopathic scoliosis remains limited. Examination of segmental spinal movement control may provide a window for investigating the features of impaired movement control specific to spinal segments that may assist in the development of physiotherapeutic management of AIS. OBJECTIVES: To compare segmental spinal movement control in adolescents with and without idiopathic scoliosis using modified pressure biofeedback unit. METHODS: Segmental spinal movement control was assessed in twenty adolescents with idiopathic scoliosis (AISG) and twenty healthy adolescents (CG) using a modified pressure biofeedback unit. Participants performed segmental spinal movements that primarily involved segmental spinal stabilizing muscles with graded and sustained muscle contraction against/off a pressure cuff from baseline to target pressures and then maintained for 1 min. Pressure data during the 1-minute maintenance phase were collected for further analysis. Pressure deviation were calculated and compared between groups. RESULTS: The AISG had significantly greater pressure deviations for all segmental spinal movements of cervical, thoracic, and lumbar spine than the CG. CONCLUSION: Pressure biofeedback unit was feasible for assessing segmental spinal movement control in AIS. AISG exhibited poorer ability to grade and sustain muscle activities for local movements of cervical, thoracic, and lumbar spine, suggesting motor control training of segmental spinal movements involving segmental spinal stabilizing muscles on frontal, sagittal, and transverse planes were required.

Encapsulation of 16-Hydroxycleroda-3,13-Dine-16,15-Olide in Mesoporous Silica Nanoparticles as a Natural Dipeptidyl Peptidase-4 Inhibitor Potentiated Hypoglycemia in Diabetic Mice.

Natural supplements comprise good efficacy with less adverse effects as against diabetic therapy, but their advancement as anti-diabetic agents is unsatisfactory with regard to the delivery system. Dipeptidyl peptidase-4 (DPP4)/CD26) can degrade glucagon-like pepetide-1 (GLP-1) which renders a decrease of blood glucose levels. 16-hydroxycleroda-3,13-dine-16,15-olide (HCD) extracted from Polyalthia longifolia, exhibits numerous medicinal potentials including hypoglycemic potential. On consideration of HCD application, the bioavailability is affected by low solubility. Extended experiments of anti-diabetic efficacy confirmed HCD biocompatible with mesoporous silica nanoparticles (MSNs) encapsulation resulted in a sustained release property in delivering HCD for the inhibition of DPP4 via the activity and protein levels of DPP4 analysis. In the enzymatic activity assay, MSN-HCD directly changed DPP4 activity. Moreover, MSN-HCD nanoparticles were treated with Caco-2 cells and the protein levels of DPP4 determined within the cells. The results revealed that MSN-HCD caused reduction of DPP4 activity in a time- and dose-dependent fashion. Orally administered MSN-HCD in diet-induced diabetic mice alleviated blood glucose via an oral glucose tolerance test. In addition, administration of MSN-HCD for five weeks revealed that the biochemical cues such as pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), triglycerides (TG), cholesterol (CHO), and glycated hemoglobin (HbA1c) in mice were commendable as further confirmation of MSN-HCD efficacy and less adverse effects in down-regulation of hyperglycemia. Furthermore, this formulation effectively controlled blood glucose and significantly decreased the body weight of mice, suggesting that MSN-HCD exerts natural DPP4 inhibitor as a potential clinical drug for the treatment of diabetes.

Phototherapeutic spectrum expansion through synergistic effect of mesoporous silica trio-nanohybrids against antibiotic-resistant gram-negative bacterium.

The extensive impact of antibiotic resistance has led to the exploration of new anti-bacterial modalities. We designed copper impregnated mesoporous silica nanoparticles (Cu-MSN) with immobilizing silver nanoparticles (SNPs) to apply photodynamic inactivation (PDI) of antibiotic-resistant E. coli. SNPs were decorated over the Cu-MSN surfaces by coordination of silver ions on diamine-functionalized Cu-MSN and further reduced to silver nanoparticles with formalin. We demonstrate that silver is capable of sensitizing the gram-negative bacteria E. coli to a gram-positive specific phototherapeutic agent in vitro; thereby expanding curcumin's phototherapeutic spectrum. The mesoporous structure of Cu-MSN remains intact after the exterior decoration with silver nanoparticles and subsequent curcumin loading through an enhanced effect from copper metal-curcumin affinity interaction. The synthesis, as well as successful assembly of the functional nanomaterials, was confirmed by various physical characterization techniques. Curcumin is capable of producing high amounts of reactive oxygen species (ROS) under light irradiation, which can further improve the silver ion release kinetics for antibacterial activity. In addition, the positive charged modified surfaces of Cu-MSN facilitate antimicrobial response through electrostatic attractions towards negatively charged bacterial cell membranes. The antibacterial action of the synthesized nanocomposites can be activated through a synergistic mechanism of energy transfer of the absorbed light from SNP to curcumin.

A focal adhesion kinase inhibitor 16-hydroxy-cleroda-3,13-dien-16,15-olide incorporated into enteric-coated nanoparticles for controlled anti-glioma drug delivery.

16-Hydroxy-cleroda-3,13-dien-16,15-olide (HCD) which is extracted from a medicinal plant, Polyalthia longifolia, was shown to exhibit anticancer activity through apoptosis and FAK inhibition in our previous study. To improve its solubility and efficacy, a novel HCD delivery system using copper-substituted mesoporous silica nanoparticles (MSNs) was designed as a delivery vehicle, and the outer surfaces of MSNs were further coated with enteric polymers to prevent the drug from leaching in the stomach acid. All the data regarding synthesis and physical characterization, including Zeta potential, FT-IR spectra, N2 adsorption-desorption isotherms (BET), drug loading, powder X-ray diffraction, Thermo gravimetric analysis (TGA), Transmission electron microscopy (TEM), and Scanning electron microscopy (SEM) were well characterized. The non-coated MSN-HCD exposed to acidic pH (1.2) showed a rapid degradation of the drug, whereas the enteric-coated samples presented a sustained release profile in the gastrointestinal pHs. Cell cytotoxicity was further confirmed by the MTT-C6 Glioma cell line, in vitro. When compared with the control and pure HCD, the MSN-HCD revealed a potential anti-proliferation effect via the synergistic effect of the drug and the MSN vehicle. Additionally, this MSN-HCD had the effect of increasing the reactive oxygen species (ROS) levels and altered the Mitochondria membrane potential (MMP) in C6 cell line. The in vivo anti-tumor efficacy of enteric-coated MSN-HCD was evaluated by C6 Glioma bearing xenograft nude mice, and enteric-coated MSN-HCD clearly exhibited the greatest anti-glioma activity, as compared to the pure HCD and the untreated control. In terms of the effective treatment of brain glioma, this study provides conclusive evidence of the successful development of the anti-cancer agent HCD conjugated with enteric-coated MSN as a delivery control mechanism with enhanced dissolution characteristics.

pH-Triggered Controllable Release of Silver-Indole-3 Acetic Acid Complexes from Mesoporous Silica Nanoparticles (IBN-4) for Effectively Killing Malignant Bacteria.

An efficient approach for the antimicrobial agent delivery specifically at acidic pH has been proposed. At the outset, functionalized mesoporous nanoparticles (NPs) were examined to verify the success of synthesis while considering the structural properties by various characterizations. The NPs were immobilized with silver-indole-3 acetic acid hydrazide (IAAH-Ag) complexes via a pH-sensitive hydrazone bond, which functioned as a model drug. When the transitional metal complexes with IBN-4-IAAH-Ag were exposed to acidic pH (near pH 5.0), the silver ions were preferentially released (70%) in a controlled manner up to 12 h by pH-sensitive denial of hydrazone bonds. In contrary, a low drug release (about 25%) was seen in physiological buffer (pH 7.4) demonstrating the pH sensitive release of this drug. Furthermore, the antibacterial efficacy of this unique structured sample was tested against the planktonic cells and biofilms of Gram-positive and Gram-negative bacteria with field emission scanning electron microscope in turn measuring the growth curves, formation of lethal reactive oxygen species, protein leakage, and DNA damage. The synthesized pH-sensitive IAAH-Ag complex was found to have high antimicrobial efficacy against multidrug resistant clinical isolates both in planktonic and biofilm states. Going forward, the synthesized nanoconjugates proved a good in vivo efficacy in treating the bacterial infection of mice. These new metal complex-conjugated NPs through a pH-sensitive hydrazone bond opened up a new avenue for the design and synthesis of the next generation antibacterial agents, which would act as an alternative to antibiotics.