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.

As the blood-brain barrier (BBB) prevents most compounds from entering the brain, nanocarrier delivery systems are frequently being explored to potentially enhance the passage of drugs due to their nanometer sizes and functional characteristics. This study aims to investigate whether Pluronic^® F68 (P68) and dequalinium (DQA) nanocarriers can improve the ability of curcumin, n-acetylcysteine (NAC) and/or deferoxamine (DFO), to access the brain, specifically target mitochondria and protect against rotenone by evaluating their effects in a combined Transwell^® hCMEC/D3 BBB and SH-SY5Y based cellular Parkinson’s disease (PD) model. P68 + DQA nanoformulations enhanced the mean passage across the BBB model of curcumin, NAC and DFO by 49%, 28% and 49%, respectively (p < 0.01, n = 6). Live cell mitochondrial staining analysis showed consistent co-location of the nanocarriers within the mitochondria. P68 + DQA nanocarriers also increased the ability of curcumin and NAC, alone or combined with DFO, to protect against rotenone induced cytotoxicity and oxidative stress by up to 19% and 14% (p < 0.01, n = 6), as measured by the MTT and mitochondrial hydroxyl radical assays respectively. These results indicate that the P68 + DQA nanocarriers were successful at enhancing the protective effects of curcumin, NAC and/or DFO by increasing the brain penetrance and targeted delivery of the associated bioactives to the mitochondria in this model. This study thus emphasises the potential effectiveness of this nanocarrier strategy in fully utilising the therapeutic benefit of these antioxidants and lays the foundation for further studies in more advanced models of PD.

Introduction: In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart’s function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease.Objectives: To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity.Methods: This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients’ treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO.Results: A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia.Conclusion: The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760.

Aim: The aim of this study is to develop dry powder formulations of azithromycin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocomposite microparticles for pulmonary delivery to improve the low bioavailability of azithromycin. Methods: Double emulsion method was used to produce nanoparticles, which were then spray dried to form nanocomposite microparticles. Encapsulation efficiency and drug loading were analysed, and formulations were characterised by particle size, zeta potential, morphology, crystallinity and in-vitro aerosol dispersion performance. Results: The addition of chitosan changed the neutrally-charged azithromycin only formulation to positively-charged nanoparticles. However, the addition of chitosan also increased the particle size of the formulations. It was observed in the NGI® data that there is an improvement in dispersibility of the chitosan-related formulations. Conclusion: It was demonstrated in this study that all dry powder formulations were able to deliver azithromycin to the deep lung regions, which suggests the potential of using azithromycin via pulmonary drug delivery as an effective method to treat COVID-19.

Background: The accelerated development of novel cancer therapies necessitates a thorough understanding of the associated cardiotoxicity profiles, due to their significant implications for the long-term health and quality of life of cancer survivors. Objectives: The aim of this study was to determine the association between cardiotoxicity and non-small cell lung cancer (NSCLC) treatments using a hospital medicines usage database in England. Methods: An observational study based on a retrospective design using real-world data from the UK DEFINE database was performed. Monthly secondary data of 40 shortlisted drugs from April 2017 to July 2022 were extracted. Results: The cardiology drug that was associated with most oncology drugs was apixaban. Atezolizumab, bevacizumab, nintedanib, osimertinib, paclitaxel, pembrolizumab, gemcitabine and vincristine were all mostly associated with apixaban, which indicated association with atrial fibrillation. Afatinib, erlotinib and methotrexate were mostly associated with atenolol, hence suggesting the association with ischaemia or hypertension. Docetaxel and epirubicin were associated with verapamil, which indicated association with arrhythmia or hypertension. Conclusions: From the correlation and regression analyses, it can be concluded that hypertension was the most associated cardiovascular disease with the 20 shortlisted oncology drugs. The findings of this study have provided a better understanding of the association between each NSCLC–Cardio drug pair.

During chronic alcohol misuse, hepatic iron overload occurs, leading to exacerbated oxidative stress and liver injury. The aim was to study formulations encapsulated with the antioxidant curcumin to assess their ability protect against oxidative stress in a model of alcohol-related liver disease (ALD) combined with iron. HepG2 (VL-17A) cells were treated with iron (50 µM) alone or with alcohol (200 to 350 mM) over 72 h and markers of oxidative damage, cell death, and mitochondrial function were assessed. Nanoformulations encapsulating curcumin were also studied. VL-17A cells treated with both ethanol and iron showed significant decreases in cell viability (64%, p < 0.0001) when compared to control, and a 56% decrease (p = 0.0279) when compared to iron-only treatment. Iron-alone treatment caused a 115% increase (p < 0.0001) in ROS at 48 h as well as increases of up to 118% when treated with 200 mM ethanol + 50 μM iron (p < 0.0001), compared to control DMEM. The study found that 10 µM curcumin DSPE-PEG increased cell viability by 17% and 41% when compared to control and iron treatment alone, respectively. Formulations reduced ROS by 36% (p = 0.0015) when compared to iron-alone treatment. In summary, encapsulated curcumin provided antioxidant capacity and reduced oxidative stress, demonstrating the therapeutic potential for curcumin formulations in ALD combined with iron dysregulation.