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467 results on '"Healy, Anne Marie"'

3. A novel thiol-saccharide mucolytic for the treatment of muco-obstructive lung diseases

Author

Addante, Annalisa, Raymond, Wilfred, Gitlin, Irina, Charbit, Annabelle, Orain, Xavier, Scheffler, Aaron Wolfe, Kuppe, Aditi, Duerr, Julia, Daniltchenko, Maria, Drescher, Marika, Graeber, Simon Y, Healy, Anne-Marie, Oscarson, Stefan, Fahy, John V, and Mall, Marcus A

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Lung, Orphan Drug, Cystic Fibrosis, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Respiratory, Good Health and Well Being, Adult, Humans, Mice, Animals, Expectorants, Sulfhydryl Compounds, Acetylcysteine, Sputum, Lung Diseases, Obstructive, Inflammation, Carbohydrates, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology
Abstract

BackgroundMucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (βENaC-Tg mice).MethodsWe compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetylcysteine (NAC) and recombinant human deoxyribonuclease I (rhDNase)) using rheology to measure the elastic modulus (G') of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in βENaC-Tg mice to determine its mucolytic efficacy in vivo.ResultsIn CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G', was faster in decreasing sputum G' by 50% and caused mucolysis of a larger proportion of sputum samples within 15 min of drug addition. Compared to vehicle control, three treatments with MUC-031 in 1 day in adult βENaC-Tg mice decreased airway mucus content (16.8±3.2 versus 7.5±1.2 nL·mm-2, p

Published
2023

10. The Use of a Three-Fluid Atomising Nozzle in the Production of Spray-Dried Theophylline/Salbutamol Sulphate Powders Intended for Pulmonary Delivery.

Author

Focaroli, Stefano, Jiang, Guannan, O'Connell, Peter, Fahy, John V, and Healy, Anne-Marie

Subjects
dry powder, dry powder inhaler, salbutamol sulphate pulmonary drug delivery, spray drying, theophylline, three-fluid nozzle, Pharmacology and Pharmaceutical Sciences
Abstract

The aim of this study was to investigate the use of a three-fluid atomising nozzle in a lab-scale spray dryer for the production of dry powders intended for pulmonary delivery. Powders were composed of salbutamol sulphate and theophylline in different weight ratios. The three-fluid nozzle technology enabled powders containing a high theophylline content to be obtained, overcoming the problems associated with its relatively low solubility, by pumping two separate feed solutions (containing the two different active pharmaceutical ingredients (APIs)) into the spray dryer via two separate nozzle channels at different feed rates. The final spray-dried products were characterized in terms of morphology, solid-state properties and aerosolization performance, and were compared with an equivalent formulation prepared using a standard two-fluid atomising nozzle. Results confirmed that most of the powders made using the three-fluid atomising nozzle met the required standards for a dry powder inhaler formulation in terms of physical characteristics; however, aerosolization characteristics require improvement if the powders are to be considered suitable for pulmonary delivery.

Published
2020

12. The use of hydrophobic amino acids in protecting spray dried trehalose formulations against moisture-induced changes

Author

Mah, Pei T, O'Connell, Peter, Focaroli, Stefano, Lundy, Ross, O'Mahony, Tom F, Hastedt, Jayne E, Gitlin, Irina, Oscarson, Stefan, Fahy, John V, and Healy, Anne Marie

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Administration, Inhalation, Aerosols, Amino Acids, Chemistry, Pharmaceutical, Drug Compounding, Dry Powder Inhalers, Humidity, Hydrophobic and Hydrophilic Interactions, Leucine, Powders, Trehalose, Wettability, Aerosolization, Hygroscopic, L-leucine, L-isoleucine, Moisture protection, Recrystallization, Spray drying, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract

Trehalose is commonly used as a protein stabilizer in spray dried protein formulations delivered via the pulmonary route. Spray dried trehalose formulations are highly hygroscopic, which makes them prone to deliquescence and recrystallization when exposed to moisture, leading to impairment in aerosolization performance. The main aim of this study was to investigate and compare the effect of hydrophobic amino acids (i.e. L-leucine and L-isoleucine) in enhancing aerosolization performance and in mitigating moisture-induced changes in spray dried trehalose formulations. Trehalose was spray dried with 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine). The spray dried formulations were stored at 25 °C/50% RH for 28 days. Solid state characterization and in vitro aerosolization performance studies were performed on the spray dried formulations before and after storage. The addition of 20-60% w/w of amino acid (i.e. L-leucine or L-isoleucine) improved the emitted fractions of spray dried trehalose formulations from a dry powder inhaler. However, ≥ 40% w/w of L-leucine/L-isoleucine was needed to prevent recrystallization of trehalose in the formulations when exposed to 25 °C/50% RH for 28 days. X-ray photoelectron spectroscopy (XPS) demonstrated that samples with 40-60% w/w L-isoleucine had more amino acid on the surfaces of the particles compared to their L-leucine counterparts. This may explain the greater ability of the L-isoleucine (40-60% w/w) samples to cope with elevated humidity compared to L-leucine samples of the same concentrations, as observed in the dynamic vapour sorption (DVS) studies. In conclusion, this study demonstrated that both L-leucine and L-isoleucine were effective in enhancing aerosolization performance and mitigating moisture-induced reduction in aerosolization performance in spray dried trehalose formulations. L-isoleucine proved to be superior to L-leucine in terms of its moisture protectant effect when incorporated at the same concentration in the formulations.

Published
2019

27. Can Amphotericin B and Itraconazole be co-delivered orally? Tailoring Oral Fixed-Dose Combination Coated Granules for Systemic Mycoses

Author

Fernández García, Raquel, Walsh, David, O'Connell, Peter, Slowing Barillas, Karla Verónica, Raposo González, Rafaela, Ballesteros Papantonakis, María De La Paloma, JImenez-Cebrian, Aurora, Chamorro Sancho, Manuel J., Bolás Fernández, Francisco, Healy, Anne Marie, Serrano López, Dolores Remedios, Fernández García, Raquel, Walsh, David, O'Connell, Peter, Slowing Barillas, Karla Verónica, Raposo González, Rafaela, Ballesteros Papantonakis, María De La Paloma, JImenez-Cebrian, Aurora, Chamorro Sancho, Manuel J., Bolás Fernández, Francisco, Healy, Anne Marie, and Serrano López, Dolores Remedios

Abstract

The incidence and prevalence of invasive fungal infections have increased significantly over the last few years, leading to a global health problem due to the lack of effective treatments. Amphotericin B (AmB) and itraconazole (ITR) are two antifungal drugs with different mechanisms of action. In this work, AmB and ITR have been formulated within granules to elicit an enhanced pharmacological effect, while enhancing the oral bioavailability of AmB. A Quality by Design (QbD) approach was utilised to prepare fixed-dose combination (FDC) granules consisting of a core containing AmB with functional excipients, such as inulin, microcrystalline cellulose (MCC), chitosan, sodium deoxycholate (NaDC) and Soluplus® and polyvinyl pyrrolidone (PVP), coated with a polymeric layer containing ITR with Soluplus® or a combination of Poloxamer 188 and hydroxypropyl methyl cellulose-acetyl succinate (HPMCAS). A Taguchi designs of experiments (DoE) with 7 factors and 2 levels was carried out to understand the key factors impacting on the physicochemical properties of the formulation followed by a Box-Behnken design with 3 factors in 3 levels chosen to optimise the formulation parameters. The core of the FDC granules was obtained by wet granulation and later coated using a fluidized bed. In vitro antifungal efficacy was demonstrated by measuring the inhibition halo against different species of Candida spp., including C. albicans (24.19-30.48 mm), C. parapsilosis (26.38-27.84 mm) and C. krusei (11.48-17.92 mm. AmB release was prolonged from 3 to 24 hours when the AmB granules were coated. In vivo in CD-1 male mice studies showed that these granules were more selective towards liver, spleen and lung compared to kidney (up to 5-fold more selective in liver, with an accumulation of 8.07 µg AmB/g liver after twice-daily 5 days administration of F2), resulting in an excellent oral administration option in the treatment of invasive mycosis. Nevertheless, some biochemical alterations were found, Banco Santander, Science Foundation Ireland, Spanish Ministry of Science and Innovation, Unión Iberoamericana de Universidades, Depto. de Farmacia Galénica y Tecnología Alimentaria, Fac. de Farmacia, FALSE, pub

Published
2023

47. Exploring antiviral and anti-inflammatory effects of thiol drugs in COVID-19

Author

Khanna, Kritika, primary, Raymond, Wilfred W., additional, Jin, Jing, additional, Charbit, Annabelle R., additional, Gitlin, Irina, additional, Tang, Monica, additional, Werts, Adam D., additional, Barrett, Edward G., additional, Cox, Jason M., additional, Birch, Sharla M., additional, Martinelli, Rachel, additional, Sperber, Hannah S., additional, Franz, Sergej, additional, Duff, Thomas, additional, Hoffmann, Markus, additional, Healy, Anne Marie, additional, Oscarson, Stefan, additional, Pöhlmann, Stefan, additional, Pillai, Satish K., additional, Simmons, Graham, additional, and Fahy, John V., additional

Published
2022
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