The effect of particle size on drug bioavailability in various parts of the body

Multiple mechanisms are involved in driving the efficacy of drug delivery. Drug particle size is one of the challenges as particles need to be delivered from the external environment, into the circulation or interstitial fluid and transiting the cell membranes for cellular internalisation. Small particles are presumably easier to be internalised, yet they are not easy to retain as they are subject to fast clearance. Big particles do not cross biological barriers as easily, but their size distribution is easier to be controlled. Because of the various routes of administration, the size range of these particles will also need to be catered for the anatomical, biological, and dynamic barriers involved. This review hopes to provide an insight into the range of particle size that has been engineered for drug delivery via various routes of administration of the body, such as to cross the epithelium of gastrointestinal tract, lungs, skin, blood-brain barrier, kidney and liver, the eye, nose, and ear, the cancer tumour matrix and into the muscles. While successful drug delivery also depends on the material properties of the delivery systems and the bio/nano interface related properties, this review focuses on the importance of particle size for enhancing bioavailability at the various organs of the body

Calcium phosphate nanoparticles for potential application as enamel remineralising agent tested on hydroxyapatite discs

Calcium phosphate nanoparticles (hydroxyapatite, 63.9 ± 15.9 nm, rod-shaped, Ca/P: 1.39, low crystallinity, calcium-deficient, carbonated) were shown to increase the surface microhardness and step height of eroded hydroxyapatite discs

Emerging nanomaterials for dental treatments

The emergence of nanomaterials for dental treatments is encouraged by the nanotopography of the tooth structure, together with the promising benefits of nanomedicine. The use of nanoparticles in dentistry, also termed as ‘nanodentistry', has manifested in applications for remineralisation, antimicrobial activity, local anaesthesia, anti-inflammation, osteoconductivity and stem cell differentiation. Besides the applications on dental tissues, nanoparticles have been used to enhance the mechanical properties of dental composites, improving their bonding and anchorage and reducing friction. The small particle size allows for enhanced permeation into deeper lesions, and reduction in porosities of dental composites for higher mechanical strength. The large surface area to volume ratio allows for enhanced bioactivity such as bonding and integration, and more intense action towards microorganisms. Controlled release of encapsulated bioactive molecules such as drugs and growth factors enables them to be delivered more precisely, with site-targeted delivery for localised treatments. These properties have benefitted across multiple fields within dentistry, including periodontology and endodontics and reengineering of dental prosthetics and braces. This review summarises the current literature on the emerging field of nanomaterials for dental treatments

Nanoparticle-enhanced mesalazine therapy for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic inflammatory illness that causes ongoing bodily inflammation in the gastrointestinal tract. Drug-targeted delivery of aminosalicylates such as mesalazine at the inflammation sites, to treat ulcerative colitis (UC) and Crohn's disease (CD) has remained a difficulty. Current mesalazine formulations, including tablets, suppositories, and enemas, are typically associated with adverse systemic effects. The use of nanocarriers however has opened the possibility of improved local targeting and pharmacokinetics of loaded mesalazine, based on the new physicochemical properties of the drug vehicle. The innovative nanoencapsulation of mesalazine has demonstrated success in targeting inflammatory regions and treating mild to moderate IBD. The use of nanocarriers, such as lipid-based, polymeric, and inorganic nanocarriers, has demonstrated improved overall solubility, absorption, and bioavailability of mesalazine while minimising the side effects associated with their absorption. This review aims to offer an insight into what is currently known about IBD, and the nanotechnological approaches for the improvement of mesalazine therapy for IBD

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Calcium phosphate nanoparticles for potential application as enamel remineralising agent tested on hydroxyapatite discs

Calcium phosphate exhibits excellent biocompatibility, and with particle size in the nanoscale, calcium phosphate nanoparticles (CPNPs) were explored to replace the hydroxyapatite lost in the nanoporous teeth due to dental erosion. CPNPs (2% w/v) colloidally stabilised by sodium citrate were synthesised via co-precipitation. They were characterised in terms of particle size, morphology, crystallinity, Ca/P ratio and calcium ion release. To ensure uniformity of the substrate, hydroxyapatite (HA) discs were examined as an alternative substrate model to enamel. They were eroded in acetate buffer (0.5 M; pH 4.0) at various timepoints (1, 5, 10, 30 min, and 2, 4 h), and their physical differences compared to enamel were assessed in terms of surface microhardness, surface roughness and step height. The remineralisation properties of the synthesised CPNPs on eroded HA discs at different pH levels were investigated. It was established that CPNPs were heterogeneously deposited on the HA discs at pH 9.2, whereas newly precipitated minerals from CPNPs were potentially formed at pH 6.2