Fabrication of inhaled hybrid silver/ciprofloxacin nanoparticles with synergetic effect against Pseudomonas aeruginosa

Ciprofloxacin (CFX) is a fluroquinolone antibiotic used as a first line treatment against infections caused by Pseudomonas aeruginosa and Streptococcus pneumonia that are commonly acquired by cystic fibrosis (CF) patients. However, no inhalation formulation is currently available for ciprofloxacin. Hybrid silica coated silver nanoparticles were prepared using Stöber reaction and the optimum ratio of chitosan and sodium tripolyphosphate was used to encapsulate CFX. Particle deposition was assessed in vitro using twin stage impinger while antimicrobial activity was evaluated based on the planktonic growth of P. aeruginosa as well as against P. aeruginosa sp biofilm formation. In vitro deposition results showed significant deposition in stage 2 using twin stage impinger (TSI) (∼70%). Compared to CFX, the formed hybrid nanoparticles were 3-4 folds more effective against inhibiting growth and biofilm formation by P. aeruginosa PAO1 and P. aeruginosa NCTC 10662

Deferoxamine and Curcumin Loaded Nanocarriers Protect Against Rotenone-Induced Neurotoxicity

Background: Reduced glutathione and excess free iron within dopaminergic, substantia nigra neurons in Parkinson's disease (PD) can drive accumulation of toxic hydroxyl radicals resulting in sustained oxidative stress and cellular damage. Factors such as brain penetrance and bioavailability have limited the advancement of potential antioxidant and iron chelator therapies for PD. Objective: This study aimed to develop novel nanocarrier delivery systems for the antioxidant curcumin and/or iron chelator deferoxamine (DFO) to protect against rotenone-induced changes in cell viability and oxidative stress in SH-SY5Y cells. Methods: Nanocarriers of curcumin and/or DFO were prepared using Pluronic F68 (P68) with or without dequilinium (DQA) by modified thin-film hydration. Cell viability was assessed using an MTT assay and oxidative stress was measured using thiobarbituric acid reactive substances and cellular antioxidant activity assays. Results: All formulations demonstrated high encapsulation efficiency (65-96%) and nanocarrier size was <200 nm. 3-h pretreatment with P68 or P68+DQA nanocarriers containing various concentrations of curcumin and/or DFO significantly protected against rotenone-reduced cell viability. The addition of DFO to curcumin-loaded P68+DQA nanocarriers resulted in increased protection by at least 10%. All nanoformulations significantly protected against rotenone-induced lipid peroxidation (p < 0.0001). The addition of DQA, which targets mitochondria, resulted in up to 65% increase in cellular antioxidant activity. In nearly all preparations, the combination of 10 μM curcumin and 100 μM DFO had the most antioxidant activity. Conclusion: This study demonstrates for the first time the formulation and delivery using P68 and P68+DQA curcumin and/or DFO nanocarriers to protect against oxidative stress induced by a rotenone PD model. This strategy to combine antioxidants with iron chelators may provide a novel approach to fully utilise their therapeutic benefit for PD

Fabrication of biopolymer based nanoparticles for the entrapment of chromium and iron supplements

The objective of this study was to encapsulate iron and chromium into novel nanoparticles formulated using chitosan (CS), dextran sulfate (DS) and whey protein isolate (WPI) for oral drug delivery. Empty and loaded CS-DS nanoparticles were prepared via complex coacervation whilst whey protein nanocarriers were produced by a modified thermal processing method using chitosan. The physiochemical properties of the particles were characterized to determine the effects of formulation variables, including biopolymer ratio on particle size and zeta potential. Permeability studies were also undertaken on the most stable whey protein–iron nanoparticles by measuring Caco-2 ferritin formation. A particle size analysis revealed that the majority of samples were sub-micron sized, ranging from 420–2400 nm for CS-DS particles and 220–1000 nm for WPI-CS samples. As expected, a higher chitosan concentration conferred a 17% more positive zeta potential on chromium-entrapped WPI nanoparticles, whilst a higher dextran volume decreased the size of CS-DS nanoparticles by 32%. The addition of iron also caused a significant increase in size for all samples, as seen where the loaded WPI samples were 296 nm larger than the empty particles. Caco-2 iron absorption revealed that one formulation, which had the lowest particle size (226 ± 10 nm), caused a 64% greater iron absorption compared to the ferrous sulfate standard. This study describes, for the first time, the novel design of chromium- and iron-entrapped nanoparticles, which could act as novel systems for oral drug delivery

Comparison study of iron preparations using a human intestinal model

Iron deficiency and related iron deficiency anaemia (IDA) are the most prevalent nutritional disorders worldwide. The standard treatment involves supple-mentation 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 demon-strated the highest iron absorption, whereas modified-release ferrous prepa-rations 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

Alcoholic liver disease: Current insights into cellular mechanisms.

Alcoholic liver disease (ALD) due to chronic alcohol consumption is a significant global disease burden and a leading cause of mortality. Alcohol abuse induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of ALD is widely recognized, the precise triggers for disease progression are still to be fully elucidated. Oxidative stress, mitochondrial dysfunction, gut dysbiosis and altered immune system response plays an important role in disease pathogenesis, triggering the activation of inflammatory pathways and apoptosis. Despite many recent clinical studies treatment options for ALD are limited, especially at the alcoholic hepatitis stage. We have therefore reviewed some of the key pathways involved in the pathogenesis of ALD and highlighted current trials for treating patients. [Abstract copyright: ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments.

Non-alcoholic fatty liver disease (NAFLD) causes significant global disease burden and is a leading cause of mortality. NAFLD induces a myriad of aberrant changes in hepatocytes at both the cellular and molecular level. Although the disease spectrum of NAFLD is widely recognised, the precise triggers for disease progression are still to be fully elucidated. Furthermore, the propagation to cirrhosis is poorly understood. Whilst some progress in terms of treatment options have been explored, an incomplete understanding of the hepatic cellular and molecular alterations limits their clinical utility. We have therefore reviewed some of the key pathways responsible for the pathogenesis of NAFLD such as innate and adaptative immunity, lipotoxicity and fibrogenesis, and highlighted current trials and treatment options for NAFLD patients. [Abstract copyright: ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.

Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a recessive genetically heterogeneous disorder of motile cilia with chronic otosinopulmonary disease and organ laterality defects in ∼50% of cases. The prevalence of PCD is difficult to determine. Recent diagnostic advances through measurement of nasal nitric oxide and genetic testing has allowed rigorous diagnoses and determination of a robust clinical phenotype, which includes neonatal respiratory distress, daily nasal congestion, and wet cough starting early in life, along with organ laterality defects. There is early onset of lung disease in PCD with abnormal airflow mechanics and radiographic abnormalities detected in infancy and early childhood

Micellar Nanocarriers of Hydroxytyrosol Are Protective against Parkinson’s Related Oxidative Stress in an In Vitro hCMEC/D3-SH-SY5Y Co-Culture System

Hydroxytyrosol (HT) is a natural phenolic antioxidant which has neuroprotective effects in models of Parkinson’s disease (PD). Due to issues such as rapid metabolism, HT is unlikely to reach the brain at therapeutic concentrations required for a clinical effect. We have previously developed micellar nanocarriers from Pluronic F68® (P68) and dequalinium (DQA) which have suitable characteristics for brain delivery of antioxidants and iron chelators. The aim of this study was to utilise the P68 + DQA nanocarriers for HT alone, or in combination with the iron chelator deferoxamine (DFO), and assess their physical characteristics and ability to pass the blood–brain barrier and protect against rotenone in a cellular hCMEC/D3-SH-SY5Y co-culture system. Both HT and HT + DFO formulations were less than 170 nm in size and demonstrated high encapsulation efficiencies (up to 97%). P68 + DQA nanoformulation enhanced the mean blood–brain barrier (BBB) passage of HT by 50% (p 0.0001, n = 6). This resulted in increased protection against rotenone induced cytotoxicity and oxidative stress by up to 12% and 9%, respectively, compared to the corresponding free drug treatments (p 0.01, n = 6). This study demonstrates for the first time the incorporation of HT and HT + DFO into P68 + DQA nanocarriers and successful delivery of these nanocarriers across a BBB model to protect against PD-related oxidative stress. These nanocarriers warrant further investigation to evaluate whether this enhanced neuroprotection is exhibited in in vivo PD models

Acute Administration of Bioavailable Curcumin Alongside Ferrous Sulphate Supplements Does Not Impair Iron Absorption in Healthy Adults in a Randomised Trial.

Ferrous sulphate (FS) is a cost effective, readily available iron supplement for iron deficiency (ID). The pro-oxidant effect of oral ferrous iron is known to induce inflammation, causing gastric side-effects and resulting in poor compliance. Curcumin is a potent antioxidant and has also been shown to exhibit iron chelation in-vitro, although it is not established whether these effects are retained in-vivo. The aim of this study was therefore to assess the influence of a formulated bioavailable form of curcumin (HydroCurc ; 500 mg) on acute iron absorption and status in a double blind, placebo-controlled randomized trial recruiting 155 healthy participants (79 males; 26.42 years ± 0.55 and 76 females; 25.82 years ± 0.54). Participants were randomly allocated to five different treatment groups: iron and curcumin placebo (FS0_Plac), low dose (18 mg) iron and curcumin placebo (FS18_Plac), low dose iron and curcumin (FS18_Curc), high dose (65 mg) iron and curcumin placebo (FS65_Plac), and high dose iron and curcumin (FS65_Curc). Participants were provided with the supplements according to their relevant treatment groups at baseline (0 min), and blood collection was carried out at 0 min and at 180 min following supplementation. In the treatment groups, significant difference was observed in mean serum iron between baseline (0 min) and at end-point (180 min) (F (1, 144) = 331.9, < 0.0001) with statistically significant intra-group increases after 180 min ( < 0.0001) in the FS18_Plac (8.79 µmol/L), FS18_Curc (11.41 µmol/L), FS65_Plac (19.09 µmol/L), and FS65_Curc (16.39 µmol/L) groups. A significant difference was also observed between the two time points in serum TIBC levels and in whole blood haemoglobin (HGB) in the treatment groups, with a significant increase (1.55%/2.04 g/L) in HGB levels from baseline to end-point observed in the FS65_Curc group ( < 0.05). All groups receiving iron demonstrated an increase in transferrin saturation (TS%) in a dose-related manner, demonstrating that increases in serum iron are translated into increases in physiological iron transportation. This study demonstrates, for the first time, that regardless of ferrous dose, formulated curcumin in the form of HydroCurc™ does not negatively influence acute iron absorption in healthy humans