Formulation of pH responsive peptides as inhalable dry powders for pulmonary delivery of nucleic acids |
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| Affiliation: | 1. Department of Pharmacology & Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region;2. Faculty of Pharmacy, The University of Sydney, Australia;3. Institute of Pharmaceutical Science, King’s College London, United Kingdom;1. Respiratory Technology, Woolcock Institute of Medical Research, Australia;2. Department of Life Sciences and Biotechnology, University of Ferrara, Italy;3. Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2037, Australia;4. Pharmaxis Pty. Ltd., 20 Rodborough Rd., Frenchs Forest, Sydney, NSW 2086, Australia;1. Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK;2. Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, USA;3. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;4. Centro de Biotecnologia, Instituto Butantan, Sao Paulo, SP, Brazil;5. Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, UK;6. UCLan Biomedical Research Facility, Research and Innovation, University of Central Lancashire, Preston, UK;7. Department of Pharmaceutics, School of Pharmacy, University College London, London, UK;1. Student Research Committee, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;2. Pharmaceutical Research Center, Department of Medicinal Chemistry, Mashhad University of Medical Sciences, Mashhad, Iran;3. Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;1. Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, 21 Sassoon Road, Hong Kong;2. School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N A1X, United Kingdom;3. Department of Biomolecular Sciences, University of Urbino, Piazza Rinascimento, 6, Urbino 61029, Italy;4. Institute of Pharmaceutical Science, King’s College London, 150 Stamford Street, London SE1 9NH, United Kingdom;1. University of Kentucky, College of Pharmacy, Department of Pharmaceutical Sciences, Drug Development Division, Lexington, KY 40536-0596, USA;2. College of Pharmacy, Chungbuk National University, Cheongju, 361-763, Republic of Korea;3. GlaxoSmithKline, Analytical Sciences, Product Development, King of Prussia, PA 19406, USA;4. The Ohio State University College of Medicine, Departments of Pediatrics and Internal Medicine, Lung and Heart-Lung Transplant Programs, Columbus, OH 43205, USA;5. The Ohio State University College of Medicine, The Davis Heart and Lung Research Institute, Columbus, OH 43205, USA;6. University of Kentucky College of Medicine, Departments of Pediatrics, Biomedical Engineering, Diagnostic Radiology, and Surgery, Lexington, KY 40536-0284, USA;7. School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea;8. University of Kentucky, Center of Membrane Sciences, Lexington, KY 40536-0596, USA;9. The University of Arizona-Tucson, College of Pharmacy, Skaggs Center of Pharmaceutical Sciences, Tucson, AZ 85721-0207, USA;1. Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales 2006, Australia;2. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China;3. Future Industries Institute, University of South Australia, Mawson Lakes, South Australia 5095, Australia;4. CSIRO Manufacturing, Bayview Avenue, Clayton, Victoria 3168, Australia |
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| Abstract: | Nucleic acids have the potential to be used as therapies or vaccines for many different types of disease, but delivery remains the most significant challenge to their clinical adoption. pH responsive peptides containing either histidine or derivatives of 2,3-diaminopropionic acid (Dap) can mediate effective DNA transfection in lung epithelial cells with the latter remaining effective even in the presence of lung surfactant containing bronchoalveolar lavage fluid (BALF), making this class of peptides attractive candidates for delivering nucleic acids to lung tissues. To further assess the suitability of pH responsive peptides for pulmonary delivery by inhalation, dry powder formulations of pH responsive peptides and plasmid DNA, with mannitol as carrier, were produced by either spray drying (SD) or spray freeze drying (SFD). The properties of the two types of powders were characterised and compared using scanning electron microscopy (SEM), next generation impactor (NGI), gel retardation and in vitro transfection via a twin stage impinger (TSI) following aerosolisation by a dry powder inhaler (Osmohaler?). Although the aerodynamic performance and transfection efficacy of both powders were good, the overall performance revealed SD powders to have a number of advantages over SFD powders and are the more effective formulation with potential for efficient nucleic acid delivery through inhalation. |
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| Keywords: | Pulmonary delivery Gene delivery Non-viral vector pH responsive Peptides Spray drying Spray freeze drying |
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