{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:00:26Z","timestamp":1781643626924,"version":"3.54.5"},"reference-count":67,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CF-Trust UK","award":["SRC013"],"award-info":[{"award-number":["SRC013"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["KU756\/14-1"],"award-info":[{"award-number":["KU756\/14-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gilead Sciences (Germany)","award":["Mucus"],"award-info":[{"award-number":["Mucus"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl\u2212 currents and intracellular Ca2+ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca2+ activated Cl\u2212 channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca2+ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres\/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.<\/jats:p>","DOI":"10.3390\/ijms23031085","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T21:01:51Z","timestamp":1642626111000},"page":"1085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Jiraporn","family":"Ousingsawat","sequence":"first","affiliation":[{"name":"Physiological Institute, University of Regensburg, University Street 31, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Centeio","sequence":"additional","affiliation":[{"name":"Physiological Institute, University of Regensburg, University Street 31, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1349-7605","authenticated-orcid":false,"given":"In\u00eas","family":"Cabrita","sequence":"additional","affiliation":[{"name":"Physiological Institute, University of Regensburg, University Street 31, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaoula","family":"Talbi","sequence":"additional","affiliation":[{"name":"Physiological Institute, University of Regensburg, University Street 31, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritz","family":"Graf","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achim","family":"G\u00f6pferich","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, University of Regensburg, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3974-5363","authenticated-orcid":false,"given":"Rainer","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Physiological Institute, University of Regensburg, University Street 31, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6222-4593","authenticated-orcid":false,"given":"Karl","family":"Kunzelmann","sequence":"additional","affiliation":[{"name":"Physiological Institute, University of Regensburg, University Street 31, 93040 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"TMEM16A in Cystic Fibrosis: Activating or Inhibiting?","volume":"29","author":"Kunzelmann","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16354","DOI":"10.1073\/pnas.1214596109","article-title":"Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction","volume":"109","author":"Huang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/cea.12887","article-title":"Chloride ion transport and overexpression of TMEM16A in a guinea pig asthma model","volume":"47","author":"Kondo","year":"2017","journal-title":"Clin. Exp. Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Caci, E., Scudieri, P., Di Carlo, E., Morelli, P., Bruno, S., De Fino, I., Bragonzi, A., Gianotti, A., Sondo, E., and Ferrera, L. (2015). Upregulation of TMEM16A Protein in Bronchial Epithelial Cells by Bacterial Pyocyanin. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131775"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1165\/rcmb.2019-0442OC","article-title":"TMEM16A Mediated Mucus Production in Human Airway Epithelial Cells","volume":"64","author":"Cabrita","year":"2020","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Centeio, R., Ousingsawat, J., Cabrita, I., Schreiber, R., Talbi, K., Benedetto, R., Dou\u0161ov\u00e1, T., Verbeken, E.K., De Boeck, K., and Cohen, I. (2021). Mucus Release and Airway Constriction by TMEM16A May Worsen Pathology in Inflammatory Lung Disease. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157852"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.1113\/jphysiol.2012.240838","article-title":"Association of TMEM16A chloride channel overexpression with airway goblet cells metaplasia","volume":"590","author":"Scudieri","year":"2012","journal-title":"J. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00424-017-2065-0","article-title":"CFTR supports cell death through ROS-dependent activation of TMEM16F (anoctamin 6)","volume":"470","author":"Simoes","year":"2018","journal-title":"Pflugers Arch."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"590","DOI":"10.33594\/000000437","article-title":"Aeruginosa Induced Lipid Peroxidation Causes Ferroptotic Cell Death in Airways","volume":"55","author":"Ousingsawat","year":"2021","journal-title":"Cell Physiol. Biochem."},{"key":"ref_10","first-page":"836","article-title":"Drugs that inhibit TMEM16 proteins block SARS-CoV-2 Spike-induced syncytia","volume":"47","author":"Braga","year":"2021","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rajah, M.M., Bernier, A., Buchrieser, J., and Schwartz, O. (2021). The Mechanism and Consequences of SARS-CoV-2 Spike-Mediated Fusion and Syncytia Formation. J. Mol. Biol., 167280.","DOI":"10.1016\/j.jmb.2021.167280"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1136\/thoraxjnl-2020-215171","article-title":"TMEM16A\/ANO1 calcium-activated chloride channel as a novel target for the treatment of human respiratory syncytial virus infection","volume":"76","author":"Pearson","year":"2020","journal-title":"Thorax"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Centeio, R., Cabrita, I., Benedetto, R., Talbi, K., Ousingsawat, J., Schreiber, R., Sullivan, J.K., and Kunzelmann, K. (2020). Pharmacological Inhibition and Activation of the Ca(2+) Activated Cl(-) Channel TMEM16A. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072557"},{"key":"ref_14","first-page":"10","article-title":"Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways","volume":"14","author":"Miner","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"128414","DOI":"10.1172\/jci.insight.128414","article-title":"Niclosamide repurposed for the treatment of inflammatory airway disease","volume":"8","author":"Cabrita","year":"2019","journal-title":"JCI Insight"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173438","DOI":"10.1016\/j.ejphar.2020.173438","article-title":"Niclosamide attenuates lung vascular remodeling in experimental pulmonary arterial hypertension","volume":"887","author":"Braga","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2693","DOI":"10.1128\/AAC.48.7.2693-2696.2004","article-title":"Inhibition of severe acute respiratory syndrome coronavirus replication by niclosamide","volume":"48","author":"Wu","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17530","DOI":"10.1074\/jbc.M112.359638","article-title":"Structure-activity analysis of niclosamide reveals potential role for cytoplasmic pH in control of mammalian target of rapamycin complex 1 (mTORC1) signaling","volume":"287","author":"Fonseca","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Prabhakara, C., Godbole, R., Sil, P., Jahnavi, S., Gulzar, S.E., van Zanten, T.S., Sheth, D., Subhash, N., Chandra, A., and Shivaraj, A. (2021). Strategies to target SARS-CoV-2 entry and infection using dual mechanisms of inhibition by acidification inhibitors. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009706"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1038\/s41467-021-24007-w","article-title":"SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals","volume":"12","author":"Gassen","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Jurgeit, A., McDowell, R., Moese, S., Meldrum, E., Schwendener, R., and Greber, U.F. (2012). Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002976"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1096\/fj.201600797RR","article-title":"Differential effects of anoctamins on intracellular calcium signals","volume":"31","author":"Cabrita","year":"2017","journal-title":"Faseb J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00424-015-1767-4","article-title":"Modulating Ca2+signals: A common theme for TMEM16, Ist2, and TMC","volume":"468","author":"Kunzelmann","year":"2016","journal-title":"Pfl\u00fcgers Arch."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chen, X., Cao, R., and Zhong, W. (2019). Host Calcium Channels and Pumps in Viral Infections. Cells, 9.","DOI":"10.3390\/cells9010094"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10822","DOI":"10.1038\/s41598-019-46856-8","article-title":"Rotavirus Calcium Dysregulation Manifests as Dynamic Calcium Signaling in the Cytoplasm and Endoplasmic Reticulum","volume":"9","author":"Perry","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5825","DOI":"10.1002\/jmv.27117","article-title":"Inhibitory effect on SARS-CoV-2 infection of neferine by blocking Ca(2+) -dependent membrane fusion","volume":"93","author":"Yang","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100084","DOI":"10.1016\/j.lanepe.2021.100084","article-title":"A randomized, double-blind, placebo-controlled phase 1 trial of inhaled and intranasal niclosamide: A broad spectrum antiviral candidate for treatment of COVID-19","volume":"4","author":"Backer","year":"2021","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_28","first-page":"400094","article-title":"Getting hands on a drug for COVID-19: Inhaled and Intranasal Niclosamide","volume":"4","author":"Kunzelmann","year":"2021","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102779","DOI":"10.1016\/j.amsu.2021.102779","article-title":"A randomised controlled trial of effectiveness and safety of Niclosamide as add on therapy to the standard of care measures in COVID-19 management","volume":"69","author":"Abdulamir","year":"2021","journal-title":"Ann. Med. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2003725","DOI":"10.1183\/13993003.03725-2020","article-title":"Early use of nitazoxanide in mild COVID-19 disease: Randomised, placebo-controlled trial","volume":"58","author":"Rocco","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.ijpharm.2005.07.023","article-title":"Comparison of the aqueous solubilization of practically insoluble niclosamide by polyamidoamine (PAMAM) dendrimers and cyclodextrins","volume":"304","author":"Devarakonda","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6410","DOI":"10.1039\/D1NR00309G","article-title":"Scalable nanoprecipitation of niclosamide and in vivo demonstration of long-acting delivery after intramuscular injection","volume":"13","author":"Hobson","year":"2021","journal-title":"Nanoscale"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/jps.22775","article-title":"Liposomes coated with chitosan-xanthan gum (chitosomes) as potential carriers for pulmonary delivery of rifampicin","volume":"101","author":"Manca","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4750","DOI":"10.1002\/ange.201913539","article-title":"Stable Polymer Nanoparticles with Exceptionally High Drug Loading by Sequential Nanoprecipitation","volume":"132","author":"Liu","year":"2020","journal-title":"Angew. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s00424-008-0543-0","article-title":"Allergen induced airway hyperresponsiveness is absent in ecto-5\u2032-nucleotidase (CD73) deficient mice","volume":"457","author":"Schreiber","year":"2008","journal-title":"Pflugers Arch."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1152\/physrev.00016.2004","article-title":"Structure and function of CLCA proteins","volume":"85","author":"Loewen","year":"2005","journal-title":"Physiol. Rev."},{"key":"ref_37","first-page":"4","article-title":"Secreted CLCA1 modulates TMEM16A to activate Ca(2+)-dependent chloride currents in human cells","volume":"4","author":"Yurtsever","year":"2015","journal-title":"Elife"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Centeio, R., Ousingsawat, J., schreiber, R., and Kunzelmann, K. (2021). CLCA1 Regulates Airway Mucus Production and Ion Secretion Through TMEM16A. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105133"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/187152809788462590","article-title":"The CLCA gene family: Putative therapeutic target for respiratory diseases","volume":"8","author":"Winpenny","year":"2009","journal-title":"Inflamm. Allergy Drug Targets"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/jcla.20009","article-title":"Digital photography: A primer for pathologists","volume":"18","author":"Riley","year":"2004","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1164\/rccm.201908-1641OC","article-title":"TMEM16A Potentiation: A Novel Therapeutic Approach for the Treatment of Cystic Fibrosis","volume":"201","author":"Danahay","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jconrel.2009.10.030","article-title":"Hydrogel-based drug delivery systems: Comparison of drug diffusivity and release kinetics","volume":"142","author":"Brandl","year":"2010","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26572","DOI":"10.1039\/C9RA03407B","article-title":"Niclosamide encapsulated polymeric nanocarriers for targeted cancer therapy","volume":"9","author":"Jain","year":"2019","journal-title":"RSC Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"496","DOI":"10.3109\/02652048.2015.1057251","article-title":"Significantly enhanced bioavailability of niclosamide through submicron lipid emulsions with or without PEG-lipid: A comparative study","volume":"32","author":"Zhang","year":"2015","journal-title":"J. Microencapsul."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.ijpharm.2019.06.019","article-title":"Hydrogel microspheres evading alveolar macrophages for sustained pulmonary protein delivery","volume":"566","author":"Graf","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108151","DOI":"10.1016\/j.exer.2020.108151","article-title":"Hyaluronic acid coating of gold nanoparticles for intraocular drug delivery: Evaluation of the surface properties and effect on their distribution","volume":"198","author":"Apaolaza","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1177\/0885328219863291","article-title":"Mucopenetrating lipoplexes modified with PEG and hyaluronic acid for CD44-targeted local siRNA delivery to the lungs","volume":"34","author":"Almeida","year":"2019","journal-title":"J. Biomater. Appl."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.actbio.2020.10.031","article-title":"Advanced materials for drug delivery across mucosal barriers","volume":"119","author":"Bandi","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"31562","DOI":"10.1038\/srep31562","article-title":"Short-term intratracheal use of PEG-modified IL-2 and glucocorticoid persistently alleviates asthma in a mouse model","volume":"6","author":"Wu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kenyon, N.J., Bratt, J.M., Lee, J., Luo, J., Franzi, L.M., Zeki, A.A., and Lam, K.S. (2013). Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077730"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1165\/ajrcmb.16.1.8998074","article-title":"Expression of CD44 isoforms is increased in the airway epithelium of asthmatic subjects","volume":"16","author":"Lackie","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1016\/S2213-2600(20)30216-2","article-title":"COVID-19 cytokine storm: The interplay between inflammation and coagulation","volume":"8","author":"Jose","year":"2020","journal-title":"Lancet. Respir. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cell.2012.07.036","article-title":"TMEM16F Forms a Ca(2+)-Activated Cation Channel Required for Lipid Scrambling in Platelets during Blood Coagulation","volume":"151","author":"Yang","year":"2012","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1096\/fj.15-280446","article-title":"Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage","volume":"30","author":"Mattheij","year":"2015","journal-title":"FASEB J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11523","DOI":"10.1038\/ncomms11523","article-title":"Phosphatidylserine exposure is required for ADAM17 sheddase function","volume":"7","author":"Sommer","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1038\/ncomms7245","article-title":"Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7-receptors in macrophages","volume":"6","author":"Ousingsawat","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"625","DOI":"10.3390\/cancers11050625","article-title":"TMEM16F\/Anoctamin 6 in Ferroptotic Cell Death","volume":"11","author":"Ousingsawat","year":"2019","journal-title":"Cancers"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.1021\/acs.biomac.1c00299","article-title":"In Situ Forming iEDDA Hydrogels with Tunable Gelation Time Release High-Molecular Weight Proteins in a Controlled Manner over an Extended Time","volume":"22","author":"Ziegler","year":"2021","journal-title":"Biomacromolecules"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.3109\/03639045.2014.954585","article-title":"Design and evaluation of injectable niclosamide nanocrystals prepared by wet media milling technique","volume":"41","author":"Ye","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/anie.200903924","article-title":"Thiol-ene click chemistry","volume":"49","author":"Hoyle","year":"2010","journal-title":"Angew. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7132","DOI":"10.1021\/ma201169z","article-title":"A Strategy for Control of \u201cRandom\u201d Copolymerization of Lactide and Glycolide: Application to Synthesis of PEG-b-PLGA Block Polymers Having Narrow Dispersity","volume":"44","author":"Qian","year":"2011","journal-title":"Macromolecules"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1039\/C8SM02189A","article-title":"Interaction of functionalized nanoparticles with serum proteins and its impact on colloidal stability and cargo leaching","volume":"15","author":"Abstiens","year":"2019","journal-title":"Soft Matter"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.cellsig.2018.01.008","article-title":"Compartmentalized crosstalk of CFTR and TMEM16A (ANO1) through EPAC1 and ADCY1","volume":"44","author":"Lerias","year":"2018","journal-title":"Cell Signal"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e3554","DOI":"10.21769\/BioProtoc.3554","article-title":"Method for Measuring Mucociliary Clearance and Cilia-generated Flow in Mice by ex vivo Imaging","volume":"10","author":"Song","year":"2020","journal-title":"Bio-Protocol"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.1016\/S0021-9258(19)83641-4","article-title":"A new generation of Ca2+ indicators with greatly improved fluorescence properties","volume":"260","author":"Grynkiewicz","year":"1985","journal-title":"J. Biol. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1085\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:04:17Z","timestamp":1760133857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/3\/1085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,19]]},"references-count":67,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23031085"],"URL":"https:\/\/doi.org\/10.3390\/ijms23031085","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,19]]}}}