Background: Respiratory diseases are mainly derived from acute and chronic inflammation of the alveoli and bronchi. The pathophysiological mechanisms of pulmonary inflammation mainly arise from oxidative damage that could ultimately lead to acute lung injury. Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations that consist of nanoparticles (NPs) have several advantages over other administration routes, and therefore, this study investigated the application of apigenin-loaded bovine serum albumin nanoparticles (BSA-Api-NPs) for pulmonary delivery. Methods: Dry powder formulations of BSA-Api-NPs were prepared by spray drying and characterized by laser diffraction particle sizing, scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. The influence of dispersibility enhancers (lactose monohydrate and l-leucine) on the in vitro aerosol deposition using a next-generation impactor was investigated in comparison to excipient-free formulation. The dissolution of Api was determined in simulated lung fluid by using the Franz cell apparatus. The antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH^⋅) free radical scavenging assay. Results: The encapsulation efficiency and the drug loading were measured to be 82.61% ± 4.56% and 7.51% ± 0.415%. The optimized spray drying conditions were suitable to produce particles with low residual moisture content. The spray-dried BSA-Api-NPs possessed good aerodynamic properties due to small and wrinkled particles with low mass median aerodynamic diameter, high emitted dose, and fine particle fraction. The aerodynamic properties were enhanced by leucine and decreased by lactose, however, the dissolution was reversely affected. The DPPH^⋅ assay confirmed that the antioxidant activity of encapsulated Api was preserved. Conclusion: This study provides evidence to support that albumin nanoparticles are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs are a novel delivery system against lung injury with potential antioxidant activity.

Introduction: Lack of time, management support, insufficient facilitates, workload balance, and culture are often reported as common barriers to physical activity (PA) participation in the workplace. In comparison, identifying facilitators of PA in the workplace are scarce. A ‘one-size-fits-all’ approach to overcoming the barriers may also be unsuccessful within university settings where multidisciplinary workforce exists due to the heterogeneity nature of job roles. Thus, the aim of this study was to understand the perceived barriers and facilitators of PA of university employees who were classified as active or inactive based on their job roles. Methods: Forty-one employees (female = 17; male = 24) participated in focus groups to discuss their perceived barriers and facilitators to PA in the workplace. Participants were categorised based on their PA levels as active and inactive prior analysing the semi-structured focus groups data via using thematic analysis. Results and Discussion: The results showed that a lack of time was reported by 80% of the participants as a barrier to PA, including 63% inactive and 17% of the active participants. This included 27% administrators’ staff, 23% academics, 19% senior management, and 11% professional service staff. Over 75% participants reported a lack of management support as one of the perceived barriers to their PA engagement in the workplace. Approximately 58% also reported workplace culture as a barrier to PA participation. Open access to a gym on campus was perceived to be the main facilitator to engaging in PA in the future. Similarly, increased management support for engaging in PA and having flexibility during working days were perceived as facilitators for PA engagement and a way to reduced sedentary behaviour in the workplace. Conclusions: These findings contribute to the limited literature in terms of evaluating obstacles and facilitators of university employees to encourage engagement with PA in the workplace. These findings can be applied to form PA, health, and wellbeing-related interventions specifically targeting these identified barriers that are experienced in the workplace and thereby potentially reducing absenteeism and increasing productivity.

Iron deficiency and related iron deficiency anaemia (IDA) are the most prevalent nutritional disorders worldwide. The standard treatment involves supplementation with solid or liquid iron supplement preparations, usually based on a ferrous salt such as ferrous sulphate, ferrous fumarate, or ferrous gluconate. In the present study, we compared iron uptake and absorption from various solid and liquid iron supplement preparations currently available in the United Kingdom using the well-characterised human epithelial adenocarcinoma cell line Caco-2. Intracellular ferritin protein formation by the Caco-2 cell was considered an indicator of cellular iron uptake and absorption. We investigated the effects of formulation ingredients at a defined pH on iron uptake and absorption, and designed a novel two-stage dissolution-absorption protocol that mimicked physiological conditions. Our experiments revealed wide variations in the rate of dissolution between the various solid iron preparations. Conventional-release ferrous iron tablets dissolved rapidly (48 ± 4 mins to 64 ± 4 mins), whereas modified-released tablets and capsules took significantly longer to undergo complete dissolution (274 ± 8 to 256 ± 8 mins). Among the solid iron preparations, ferrous sulphate conventional-release tablets demonstrated the highest iron absorption, whereas modified-release ferrous preparations demonstrated uniformly low iron absorption, as compared to the control (P < 0.05). Taken together, our results demonstrate that there are wide-ranging variations in dissolution times and iron uptake from oral iron preparations, with the physical characteristics of the preparation as well as the form of iron playing a key role.

The prevalence of obesity has been increasing at a rapid rate over the last few decades. Although the primary defect can be attributed to an imbalance of energy intake over energy expenditure, the regulation of energy balance is now recognized to be complex. Adipose-tissue factors play a central role in the control of energy balance and whole-body fuel homoeostasis. The regulation of adipose-tissue function, in particular its secretion of adipokines, is impaired by increases in adipose mass associated with obesity, and with the development of insulin resistance and Type 2 diabetes. This review analyses adipose-regulated energy input and expenditure, together with the impact of dietary macronutrient composition on energy balance in relation to susceptibility to the development of obesity and Type 2 diabetes, and how these metabolic conditions may be exacerbated by the consequences of abnormal adipose function. By gaining a greater understanding of how energy balance is controlled in normal, and in obese and diabetic states, a more practical approach can be employed to prevent and better treat obesity and metabolic disorders.

Oxidative stress is a key mediator in the development and progression of Parkinson’s disease (PD). The antioxidant N-acetylcysteine (NAC) has generated interest as a disease-modifying therapy for PD but is limited due to poor bioavailability, a short half-life, and limited access to the brain. The aim of this study was to formulate and utilise mitochondria-targeted nanocarriers for delivery of NAC alone and in combination with the iron chelator deferoxamine (DFO), and assess their ability to protect against oxidative stress in a cellular rotenone PD model. Pluronic F68 (P68) and dequalinium (DQA) nanocarriers were prepared by a modified thin-film hydration method. An MTT assay assessed cell viability and iron status was measured using a ferrozine assay and ferritin immunoassay. For oxidative stress, a modified cellular antioxidant activity assay and the thiobarbituric acid-reactive substances assay and mitochondrial hydroxyl assay were utilised. Overall, this study demonstrates, for the first time, successful formulation of NAC and NAC + DFO into P68 + DQA nanocarriers for neuronal delivery. The results indicate that NAC and NAC + DFO nanocarriers have the potential characteristics to access the brain and that 1000 μM P68 + DQA NAC exhibited the strongest ability to protect against reduced cell viability (p = 0.0001), increased iron (p = 0.0033) and oxidative stress (p ≤ 0.0003). These NAC nanocarriers therefore demonstrate significant potential to be transitioned for further preclinical testing for PD.

Obesity‐related metabolic disorders are characterized by mild chronic inflammation, leukocyte infiltration, and tissue fibrosis as a result of adipocytokine production from the expanding white adipose tissue. Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein, which modulates systemic anti‐inflammatory processes and, therefore, may be altered with increasing adiposity in humans. Paradoxically, we found that plasma AnxA1 concentrations inversely correlated with BMI, total percentage body fat, and waist‐to‐hip ratio in human subjects. Plasma AnxA1 was also inversely correlated with plasma concentrations of the acute‐phase protein, C‐reactive protein (CRP), and the adipocytokine leptin, suggesting that as systemic inflammation increases, anti‐inflammatory AnxA1 is reduced. In addition, AnxA1 gene expression and protein were significantly up‐regulated during adipogenesis in a human adipocyte cell line compared to vehicle alone, demonstrating for the first time that AnxA1 is expressed and excreted from human adipocytes. These data demonstrate a failure in the endogenous anti‐inflammatory system to respond to increasing systemic inflammation resulting from expanding adipose tissue, a condition strongly linked to the development of type 2 diabetes and cardiovascular disease. These data raise the possibility that a reduction in plasma AnxA1 may contribute to the chronic inflammatory phenotype observed in human obesity.—Kosicka, A., Cunliffe, A. D., Mackenzie, R., Gulrez Zariwala, M., Perretti, M., Flower, R. J., Renshaw, D. Attenuation of plasma annexin A1 in human obesity. FASEB J. 27, 368–378 (2013). www.fasebj.org