Proapoptotic lipid nanovesicles: Synergism with paclitaxel in human lung adenocarcinoma A549 cells |
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| Authors: | Nitin Joshi Thanigaivel Shanmugam Anubhav Kaviratna Rinti Banerjee |
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| Affiliation: | 1. Faculty of Pharmacy, Albaath University, Homs, Syria;2. Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom;3. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom;4. School of Medicine and Dentistry, University of Central Lancashire, Preston PR1 2HE, United Kingdom;5. Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom;1. Institute of Nanotechnology and Bioengineering, University of Central Lancashire, Preston PR1 2HE, United Kingdom;2. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom;3. School of Medicine, University of Central Lancashire, Preston PR1 2HE, United Kingdom;4. Faculty of Medical Science, Anglia Ruskin University, Bishops Hall Lane, Chelmsford CM1 1SQ, United Kingdom;5. Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom;6. Pharmaceutical Sciences Section, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar;1. Department of Chemistry, School of Sciences & Engineering, The American University in Cairo, Cairo, Egypt;2. Laboratory of Pharmaceutical Technology and Biopharmaceutics, University of Bonn, Bonn, Germany;3. Laboratory of Pharmaceutical Engineering, University of Franche-Comté, Besançon, France;4. Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt;5. Department of Chemistry, Institute of Physical Chemistry, University of Cologne, Cologne, Germany;6. Department of Chemistry, Institute of Inorganic Chemistry, University of Cologne, Cologne, Germany;1. Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, United States;2. Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, United States;1. Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan;2. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;3. Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;4. School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan;5. School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan;6. Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan;7. Cancer Center, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan;8. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan;9. Institute of Primary Care and Public Health, Cardiff University, Cardiff, Wales, UK;10. School of Earth and Ocean Sciences, Cardiff University, Cardiff, Wales, UK;11. School of Biosciences, Cardiff University, Cardiff, Wales, UK;12. Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan;13. Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan |
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| Abstract: | The present study focuses on the development and evaluation of phosphatidylserine based proapoptotic lipid nanovesicles (PSN-PTX) as aerosols for synergistic activity with paclitaxel against lung cancer. PSN-PTX showed a unimodal size distribution of the particles (100–200 nm), negative surface charge of ? 29 mV and high encapsulation efficiency of paclitaxel (82%) with 19% of it releasing in 48 h. PSN-PTX was found to be highly surface active as compared to Taxol®, marketed formulation of paclitaxel, whose surface activity was found to be detrimental for pulmonary mechanics. PSN-PTX also showed high airway patency in capillary surfactometer unlike Taxol®, suggesting its ability to mimic pulmonary surfactant functions. High deposition of PSN-PTX in lower impingement chamber of twin impinger upon nebulization suggested it to be capable of reaching the terminal regions of the lungs. Nanovesicles showed facilitated and ATP dependent active uptake by A549 cells. The combination of phosphatidylserine nanovesicles and paclitaxel as PSN-PTX enhanced cytotoxicity in A549 cell line showing an IC50 of 18 nM which is10-50 folds less than the IC50 values observed for blank phosphtidylserine nanovesicles and paclitaxel alone. Further, the combination index was found to be less than one which indicates a synergism of the two components. DNA fragmentation study showed that blank phosphatidylserine nanovesicles induce apoptosis in A549 cells and hence behave as proapoptotic nanovesicles in the combination therapy. Overall, these studies suggest the therapeutic potential and advantages of combination chemotherapy of proapoptotic lipid nanovesicles with encapsulated paclitaxel and their feasibility for aerosol administration in the treatment of lung cancer. |
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