Anisotropic diffusion of water molecules in hydroxyapatite nanopores

Funded by EPSRC Grant EP/K000128/1

Putative Nanobacteria Represent Physiological Remnants and Culture By-Products of Normal Calcium Homeostasis

Putative living entities called nanobacteria (NB) are unusual for their small sizes (50–500 nm), pleomorphic nature, and accumulation of hydroxyapatite (HAP), and have been implicated in numerous diseases involving extraskeletal calcification. By adding precipitating ions to cell culture medium containing serum, mineral nanoparticles are generated that are morphologically and chemically identical to the so-called NB. These nanoparticles are shown here to be formed of amorphous mineral complexes containing calcium as well as other ions like carbonate, which then rapidly acquire phosphate, forming HAP. The main constituent proteins of serum-derived NB are albumin, fetuin-A, and apolipoprotein A1, but their involvement appears circumstantial since so-called NB from different body fluids harbor other proteins. Accordingly, by passage through various culture media, the protein composition of these particles can be modulated. Immunoblotting experiments reveal that antibodies deemed specific for NB react in fact with either albumin, fetuin-A, or both, indicating that previous studies using these reagents may have detected these serum proteins from the same as well as different species, with human tissue nanoparticles presumably absorbing bovine serum antigens from the culture medium. Both fetal bovine serum and human serum, used earlier by other investigators as sources of NB, paradoxically inhibit the formation of these entities, and this inhibition is trypsin-sensitive, indicating a role for proteins in this inhibitory process. Fetuin-A, and to a lesser degree albumin, inhibit nanoparticle formation, an inhibition that is overcome with time, ending with formation of the so-called NB. Together, these data demonstrate that NB are most likely formed by calcium or apatite crystallization inhibitors that are somehow overwhelmed by excess calcium or calcium phosphate found in culture medium or in body fluids, thereby becoming seeds for calcification. The structures described earlier as NB may thus represent remnants and by-products of physiological mechanisms used for calcium homeostasis, a concept which explains the vast body of NB literature as well as explains the true origin of NB as lifeless protein-mineralo entities with questionable role in pathogenesis

Implications and emerging control strategies for ventilator-associated infections

© 2015 Informa UK, Ltd Ventilator-associated pneumonia (VAP) remains a major burden to the healthcare system and intubated patients in intensive care units. In fact, VAP is responsible for at least 50% of prescribed antibiotics to patients who need mechanical ventilation. One of the factors contributing to VAP pathogenesis is believed to be rapid colonization of biofilm-forming pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus on the surface of inserted endotracheal tubes. These biofilms serve as a protective environment for bacterial colonies and provide enhanced resistance towards many antibiotics. This review presents and discusses an overview of current strategies to inhibit the colonization and formation of biofilm on endotracheal tubes, including antibiotic treatment, surface modification and antimicrobial agent incorporation onto endotracheal tube materials

Superhydrophobic, nanotextured polyvinyl chloride films for delaying Pseudomonas aeruginosa attachment to intubation tubes and medical plastics

Bacterial attachment onto the surface of polymers in medical devices such as polyvinyl chloride (PVC) is influenced by the physicochemical properties of the polymer, including its surface hydrophobicity and roughness. In this study, to prevent biofilm formation onto PVC devices, the PVC surface was modified using a combination of solvent (tetrahydrofuran) and non-solvents (i.e. ethanol and methanol). The surface of unmodified PVC was smooth and relatively hydrophobic (water contact angle (CA) = 80°). Ethanol-treated PVCs revealed the presence of micron-sized particulates and porous structures as the concentration of ethanol was increased. Surface hydrophobicity (measured in terms of CA) increased from 73° to 150° as the ethanol concentration increased from 15% to 35% (v/v). In general, methanol-treated PVCs were more hydrophilic compared to those treated with ethanol. The colonization of Pseudomonas aeruginosa PAO1 onto unmodified PVC surface was rapid, and individual bacterial cells could be seen after 6 h incubation. On the surface of treated PVC, the secretion of extracellular matrix layers was evident at 18 h and P. aeruginosa PAO1 start to form microcolonies at 24 h of incubation. The initial attachment of P. aeruginosa PAO1 was delayed to 18 and 24 h, respectively in the PVCs treated with 25% (v/v) and 35% (v/v) ethanol. It can be concluded that the treatment used in this study to prepare superhydrophobic PVC surface prevented the colonization of bacteria up to 24 h after culture. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved

Fabrication of curcumin micellar nanoparticles with enhanced anti-cancer activity

Copyright © 2015 American Scientific Publishers. All rights reserved. Although curcumin is effective in killing cancer cells, its low water solubility and inadequate bioavailability remain major limitations to its therapeutic application. Formulating curcumin micellar nanoparticles (Cur-NPs) encapsulated with a biodegradable polymer can significantly improve curcumin's solubility, stability, and bioavailability in vitro. In this study, differently sized Cur-NPs coated with polyvinyl alcohol (PVA) were engineered. The particle size, encapsulation efficiency, in vitro release, stability, cytotoxicity, and cellular uptake of these Cur-NPs were characterized in several cancer cell lines. The results showed that, relative to solubilized curcumin, Cur-NPs demonstrated higher cytotoxicity against cancer cells. To our knowledge, this study is the first to demonstrate that the extent of the anti-cancer potency and cellular uptake of Cur-NPs is directly correlated to particle size, where Cur-NPs with the smallest size (28 nm) were the most potent. Confocal microscopy revealed the subcellular localization of the smaller Cur-NPs (28 nm) to be in both the nucleus and cytoplasm, while the larger particles (200 nm) were only localized in the cytoplasm

Silver nanoparticles enhance Pseudomonas aeruginosa PAO1 biofilm detachment

Objectives: Silver nanoparticles (AgNPs) with a size ranging from 7 to 70 nm were synthesized using the ascorbic acid-citrate seed-mediated growth approach at room temperature. Methods: The 8 nm silver particles were prepared using gallic acid in alkaline conditions and used as seed to prepare AgNPs. Results: The presence of ascorbic acid and citrate allows the regulation of size and size distribution of the nanoparticles. The increase in free silver ion-to-seed ratio (Ag+/Ag0) resulted in changes of particle shape from spherical to pseudo-spherical and minor cylindrical shape. Further, a repetitive seeding approach resulted in the formation of pseudo-spherical particles with higher polydispersity index and minor distributions of tetrahedral particles. Citrate-capped AgNPs were stable and did not agglomerate upon centrifugation. The effect of AgNPs on biofilm reduction was evaluated using static culture on 96-well microtiter plates. Results showed that AgNPs with the smallest average diameter were most effective in the reduction of Pseudomonas aeruginosa biofilm colonies, which accounted for 90% of removal. Conclusion: The biofilm removal activities of the nanoparticles were found to be concentration-independent particularly for the concentration within the range of 80-200 μg/mL. © 2014 Informa Healthcare USA, Inc

Synthesis of stabilized hydroxyapatite nanosuspensions for enamel caries remineralization

© 2018 Australian Dental Association Background: The aim of this study was to develop and evaluate a method for synthesizing a stable suspension of hydroxyapatite nanoparticles and to test its efficacy for remineralizing carious enamel lesions. Methods: Hydroxyapatite (HA) particles were synthesized using wet chemistry. Synthesized particles were introduced into a high-pressure homogenizer (5–10 homogenization passes at 15 000 psi) in the presence of different stabilizers. Size and distribution of the resultant particles were determined using dynamic light scattering (DLS). The morphology and composition of the nanoparticles were determined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). Subsequently, artificial lesions were treated with HA nanosuspension plus artificial saliva or a fluoride-containing artificial saliva only. Visual analysis and quantification of the lesion mineral density before and after remineralization were performed using microcomputed tomography. Results: DLS and SEM results confirmed the formation of nonagglomerated HA nanoparticles (20–40 nm) following high-pressure homogenization treatment. Quantitative evaluation of the lesions showed that remineralization of the lesion with hydroxyapatite nanosuspension led to a significantly higher level of mineral gain compared to the control group (P < 0.05). Conclusion: High-pressure homogenization is an effective method for facile preparation of a stable suspension of hydroxyapatite nanoparticles. Treatment of artificial lesions with nonagglomerated spherical HA nanoparticles improves the remineralization of enamel lesion

Non-cytotoxic silver nanoparticle-polyvinyl alcohol hydrogels with anti-biofilm activity: Designed as coatings for endotracheal tube materials

Endotracheal intubation is commonly associated with hospital-acquired infections as the intubation device acts as reservoir for bacterial colonization in the lungs. To reduce the incidence of bacterial colonization on the tubes, hydrogel coatings loaded with antimicrobial agents are gaining popularity. The aim of this study was to incorporate silver nanoparticles (AgNPs) into polyvinyl alcohol (PVA) to form stable hydrogels. Embedding AgNPs into PVA resulted in a decreased elongation at break and an increased tensile strength compared to PVA alone. The Ag release profile varied as a function of the degree of hydrolysis of PVA: the higher degree of hydrolysis demonstrated a lower release rate. Fourier infrared transform spectroscopy demonstrated that AgNPs interacted exclusively with the -OH groups of PVA. AgNP-loaded PVA was non-toxic against human normal bronchial epithelial cells while effective against the attachment of Pseudomonas aeruginosa and Staphylococcus aureus with a greater effect on P. aeruginosa. © 2014 © 2014 Taylor & Francis

Curcumin and its derivatives: Their application in neuropharmacology and neuroscience in the 21^st century

© 2013, BenthamScience Publishers. Curcumin (diferuloylmethane), a polyphenol extracted from the plant Curcuma longa, is widely used in Southeast Asia, China and India in food preparation and for medicinal purposes. Since the second half of the last century, this traditional medicine has attracted the attention of scientists from multiple disciplines to elucidate its pharmacological properties. Of significant interest is curcumin’s role to treat neurodegenerative diseases including Alzheimer’s disease (AD), and Parkinson’s disease (PD) and malignancy. These diseases all share an inflammatory basis, involving increased cellular reactive oxygen species (ROS) accumulation and oxidative damage to lipids, nucleic acids and proteins. The therapeutic benefits of curcumin for these neurodegenerative diseases appear multifactorial via regulation of transcription factors, cytokines and enzymes associated with (Nuclear factor kappa beta) NFκB activity. This review describes the historical use of curcumin in medicine, its chemistry, stability and biological activities, including curcumin's anti-cancer, anti-microbial, anti-oxidant, and anti-inflammatory properties. The review further discusses the pharmacology of curcumin and provides new perspectives on its therapeutic potential and limitations. Especially, the review focuses in detail on the effectiveness of curcumin and its mechanism of actions in treating neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases and brain malignancies