Delivery of Agarose-aided Sprays to the Posterior Nose for Mucosa Immunization and Short-term Protection against Infectious Respiratory Diseases


Cite item

Full Text

Abstract

Aim:The study aimed to deliver sprays to the posterior nose for mucosa immunization or short-term protection.

Background:Respiratory infectious diseases often enter the human body through the nose. Sars- Cov-2 virus preferentially binds to the ACE2-rich tissue cells in the Nasopharynx (NP). Delivering medications to the nose, especially to the NP region, provides either a short-term protective/ therapeutic layer or long-term mucosa immunization. Hydrogel-aided medications can assist film formation, prolong film life, and control drug release. However, conventional nasal sprays have failed to dispense mediations to the posterior nose, with most sprays lost in the nasal valve and front turbinate.

Objective:The objective of the study was to develop a practical delivery system targeting the posterior nose and quantify the dosimetry distribution of agarose-saline solutions in the nasal cavity.

Methods:The solution viscosities with various hydrogel concentrations (0.1-1%) were measured at different temperatures. Dripping tests on a vertical plate were conducted to understand the hydrogel concentration effects on the liquid film stability and mobility. Transparent nasal airway models were used to visualize the nasal spray deposition and liquid film translocation.

Result:Spray dosimetry with different hydrogel concentrations and inhalation flow rates was quantified on a total and regional basis. The solution viscosity increased with decreasing temperature, particularly in the range of 60-40oC. The liquid viscosity, nasal spray atomization, and liquid film mobility were highly sensitive to the hydrogel concentration. Liquid film translocations significantly enhanced delivered doses to the caudal turbinate and nasopharynx when the sprays were administered at 60oC under an inhalation flow rate of 11 L/min with hydrogel concentrations no more than 0.5%. On the other hand, sprays with 1% hydrogel or administered at 40oC would significantly compromise the delivered doses to the posterior nose.

Conclusion:Delivering sufficient doses of hydrogel sprays to the posterior nose is feasible by leveraging the post-administration liquid film translocation.

About the authors

Amr Seifelnasr

Department of Biomedical Engineering, University of Massachusetts

Email: info@benthamscience.net

Mohamed Talaat

Department of Biomedical Engineering, University of Massachusetts

Email: info@benthamscience.net

Xiuhua Si

Department of Aerospace, Industrial, and Mechanical Engineering,, California Baptist University,

Email: info@benthamscience.net

Jinxiang Xi

Department of Biomedical Engineering, University of Massachusetts

Author for correspondence.
Email: info@benthamscience.net

References

  1. Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.R.; Zhu, Y.; Li, B.; Huang, C.L.; Chen, H.D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R.D.; Liu, M.Q.; Chen, Y.; Shen, X.R.; Wang, X.; Zheng, X.S.; Zhao, K.; Chen, Q.J.; Deng, F.; Liu, L.L.; Yan, B.; Zhan, F.X.; Wang, Y.Y.; Xiao, G.F.; Shi, Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798), 270-273. doi: 10.1038/s41586-020-2012-7 PMID: 32015507
  2. Seo, G.; Lee, G.; Kim, M.J.; Baek, S.H.; Choi, M.; Ku, K.B.; Lee, C.S.; Jun, S.; Park, D.; Kim, H.G.; Kim, S.J.; Lee, J.O.; Kim, B.T.; Park, E.C.; Kim, S.I. Rapid detection of COVID-19 causative virus (SARS-CoV-2) in human nasopharyngeal swab specimens using field-effect transistor-based biosensor. ACS Nano, 2020, 14(4), 5135-5142. doi: 10.1021/acsnano.0c02823 PMID: 32293168
  3. Shawon, J.; Akter, Z.; Hossen, M.M.; Akter, Y.; Sayeed, A.; Junaid, M.; Afrose, S.S.; Khan, M.A. Current landscape of natural products against coronaviruses: perspectives in COVID-19 treatment and anti-viral mechanism. Curr. Pharm. Des., 2020, 26(41), 5241-5260. doi: 10.2174/1381612826666201106093912 PMID: 33155902
  4. Ferrer, G.; Sanchez-Gonzalez, M.A. Effective nasal disinfection as an overlooked strategy in our fight against COVID-19. Ear Nose Throat J., 2021, 1455613211002929. PMID: 33765853
  5. Figueroa, J.M.; Lombardo, M.E.; Dogliotti, A.; Flynn, L.P.; Giugliano, R.; Simonelli, G.; Valentini, R.; Ramos, A.; Romano, P.; Marcote, M.; Michelini, A.; Salvado, A.; Sykora, E.; Kniz, C.; Kobelinsky, M.; Salzberg, D.M.; Jerusalinsky, D.; Uchitel, O. Efficacy of a nasal spray containing Iota-Carrageenan in the postexposure prophylaxis of COVID-19 in hospital personnel dedicated to patients care with COVID-19 disease. Int. J. Gen. Med., 2021, 14, 6277-6286. doi: 10.2147/IJGM.S328486 PMID: 34629893
  6. Lavelle, E.C.; Ward, R.W. Mucosal vaccines — fortifying the frontiers. Nat. Rev. Immunol., 2022, 22(4), 236-250. doi: 10.1038/s41577-021-00583-2 PMID: 34312520
  7. Guo, Y.; Laube, B.; Dalby, R. The effect of formulation variables and breathing patterns on the site of nasal deposition in an anatomically correct model. Pharm. Res., 2005, 22(11), 1871-1878. doi: 10.1007/s11095-005-7391-9 PMID: 16091994
  8. Li, Q.; Shao, X.; Dai, X.; Guo, Q.; Yuan, B.; Liu, Y.; Jiang, W. Recent trends in the development of hydrogel therapeutics for the treatment of central nervous system disorders. NPG Asia Mater., 2022, 14(1), 14. doi: 10.1038/s41427-022-00362-y
  9. Udeni Gunathilake, T.; Ching, Y.; Chuah, C. Enhancement of curcumin bioavailability using nanocellulose reinforced chitosan hydrogel. Polymers (Basel), 2017, 9(12), 64. doi: 10.3390/polym9020064 PMID: 30970742
  10. Cao, H.; Duan, L.; Zhang, Y.; Cao, J.; Zhang, K. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal Transduct. Target. Ther., 2021, 6(1), 426. doi: 10.1038/s41392-021-00830-x PMID: 34916490
  11. Buwalda, S.J.; Vermonden, T.; Hennink, W.E. Hydrogels for therapeutic delivery: current developments and future directions. Biomacromolecules, 2017, 18(2), 316-330. doi: 10.1021/acs.biomac.6b01604 PMID: 28027640
  12. Nikjoo, D.; van der Zwaan, I.; Brülls, M.; Tehler, U.; Frenning, G. Hyaluronic acid hydrogels for controlled pulmonary drug delivery—a particle engineering approach. Pharmaceutics, 2021, 13(11), 1878. doi: 10.3390/pharmaceutics13111878 PMID: 34834293
  13. Stocke, N.A.; Arnold, S.M.; Zach Hilt, J. Responsive hydrogel nanoparticles for pulmonary delivery. J. Drug Deliv. Sci. Technol., 2015, 29, 143-151. doi: 10.1016/j.jddst.2015.06.013 PMID: 26339298
  14. Ousingsawat, J.; Centeio, R.; Cabrita, I.; Talbi, K.; Zimmer, O.; Graf, M.; Göpferich, A.; Schreiber, R.; Kunzelmann, K. Airway delivery of hydrogel-encapsulated niclosamide for the treatment of inflammatory airway aisease. Int. J. Mol. Sci., 2022, 23(3), 1085. doi: 10.3390/ijms23031085 PMID: 35163010
  15. Cunha, S.; Swedrowska, M.; Bellahnid, Y.; Xu, Z.; Sousa Lobo, J.M.; Forbes, B.; Silva, A.C. Thermosensitive In situ hydrogels of rivastigmine-loaded lipid-based nanosystems for nose-to-brain delivery: characterisation, biocompatibility, and drug deposition studies. Int. J. Pharm., 2022, 620, 121720. doi: 10.1016/j.ijpharm.2022.121720 PMID: 35413397
  16. Akel, H.; Ismail, R.; Csóka, I. Progress and perspectives of brain-targeting lipid-based nanosystems via the nasal route in Alzheimer’s disease. Eur. J. Pharm. Biopharm., 2020, 148, 38-53. doi: 10.1016/j.ejpb.2019.12.014 PMID: 31926222
  17. Cheng, S.; Wang, H.; Pan, X.; Zhang, C.; Zhang, K.; Chen, Z.; Dong, W.; Xie, A.; Qi, X. Dendritic hydrogels with robust inherent antibacterial properties for promoting bacteria-infected wound healing. ACS Appl. Mater. Interfaces, 2022, 14(9), 11144-11155. doi: 10.1021/acsami.1c25014 PMID: 35195389
  18. Xiang, Y.; Qi, X.; Cai, E.; Zhang, C.; Wang, J.; Lan, Y.; Deng, H.; Shen, J.; Hu, R. Highly efficient bacteria-infected diabetic wound healing employing a melanin-reinforced biopolymer hydrogel. Chem. Eng. J., 2023, 460, 141852. doi: 10.1016/j.cej.2023.141852
  19. Costa-Almeida, R.; Calejo, I.; Altieri, R.; Domingues, R.M.A.; Giordano, E.; Reis, R.L.; Gomes, M.E. Exploring platelet lysate hydrogel-coated suture threads as biofunctional composite living fibers for cell delivery in tissue repair. Biomed. Mater., 2019, 14(3), 034104. doi: 10.1088/1748-605X/ab0de6 PMID: 30844766
  20. Salati, M.A.; Khazai, J.; Tahmuri, A.M.; Samadi, A.; Taghizadeh, A.; Taghizadeh, M.; Zarrintaj, P.; Ramsey, J.D.; Habibzadeh, S.; Seidi, F.; Saeb, M.R.; Mozafari, M. Agarose-based biomaterials: opportunities and challenges in cartilage tissue engineering. Polymers (Basel), 2020, 12(5), 1150. doi: 10.3390/polym12051150 PMID: 32443422
  21. Kim, C.; Jeong, D.; Kim, S.; Kim, Y.; Jung, S. Cyclodextrin functionalized agarose gel with low gelling temperature for controlled drug delivery systems. Carbohydr. Polym., 2019, 222, 115011. doi: 10.1016/j.carbpol.2019.115011 PMID: 31320040
  22. Hafezi, M.; Qin, L.; Mahmoodi, P.; Dong, G. Osmosis effect on protein sustained release of Agarose hydrogel for anti-friction performance. Tribol. Int., 2019, 132, 108-117. doi: 10.1016/j.triboint.2018.12.013
  23. Hasan, M.L.; Padalhin, A.R.; Kim, B.; Lee, B.T. Preparation and evaluation of BCP‐CSD‐agarose composite microsphere for bone tissue engineering. J. Biomed. Mater. Res. B Appl. Biomater., 2019, 107(7), 2263-2272. doi: 10.1002/jbm.b.34318 PMID: 30676689
  24. Tripathi, A.; Kumar, A. Multi-featured macroporous agarose-alginate cryogel: synthesis and characterization for bioengineering applications. Macromol. Biosci., 2011, 11(1), 22-35. doi: 10.1002/mabi.201000286 PMID: 21077225
  25. Awadhiya, A.; Kumar, D.; Rathore, K.; Fatma, B.; Verma, V. Synthesis and characterization of agarose–bacterial cellulose biodegradable composites. Polym. Bull., 2017, 74(7), 2887-2903. doi: 10.1007/s00289-016-1872-3
  26. Pearl, G.S.; Check, I.J.; Hunter, R.L. Agarose electrophoresis and immunonephelometric quantitation of cerebrospinal fluid immunoglobulins: criteria for application in the diagnosis of neurologic disease. Am. J. Clin. Pathol., 1984, 81(5), 575-580. doi: 10.1093/ajcp/81.5.575 PMID: 6720628
  27. Zheng, H.; Lang, Y.; Yu, J.; Han, Z.; Chen, B.; Wang, Y. Affinity binding of aptamers to agarose with DNA tetrahedron for removal of hepatitis B virus surface antigen. Colloids Surf. B Biointerfaces, 2019, 178, 80-86. doi: 10.1016/j.colsurfb.2019.02.040 PMID: 30844563
  28. Bachelder, E.M.; Beaudette, T.T.; Broaders, K.E.; Dashe, J.; Fréchet, J.M.J. Acetal-derivatized dextran: an acid-responsive biodegradable material for therapeutic applications. J. Am. Chem. Soc., 2008, 130(32), 10494-10495. doi: 10.1021/ja803947s PMID: 18630909
  29. Broaders, K.E.; Cohen, J.A.; Beaudette, T.T.; Bachelder, E.M.; Fréchet, J.M.J. Acetalated dextran is a chemically and biologically tunable material for particulate immunotherapy. Proc. Natl. Acad. Sci. USA, 2009, 106(14), 5497-5502. doi: 10.1073/pnas.0901592106 PMID: 19321415
  30. Chen, N.; Johnson, M.M.; Collier, M.A.; Gallovic, M.D.; Bachelder, E.M.; Ainslie, K.M. Tunable degradation of acetalated dextran microparticles enables controlled vaccine adjuvant and antigen delivery to modulate adaptive immune responses. J. Control. Release, 2018, 273, 147-159. doi: 10.1016/j.jconrel.2018.01.027 PMID: 29407676
  31. Kretzer, C.; Shkodra, B.; Klemm, P.; Jordan, P.M.; Schröder, D.; Cinar, G.; Vollrath, A.; Schubert, S.; Nischang, I.; Hoeppener, S.; Stumpf, S.; Banoglu, E.; Gladigau, F.; Bilancia, R.; Rossi, A.; Eggeling, C.; Neugebauer, U.; Schubert, U.S.; Werz, O. Ethoxy acetalated dextran-based nanocarriers accomplish efficient inhibition of leukotriene formation by a novel FLAP antagonist in human leukocytes and blood. Cell. Mol. Life Sci., 2022, 79(1), 40. doi: 10.1007/s00018-021-04039-7 PMID: 34971430
  32. Meenach, S.A.; Kim, Y.J.; Kauffman, K.J.; Kanthamneni, N.; Bachelder, E.M.; Ainslie, K.M. Synthesis, optimization, and characterization of camptothecin-loaded acetalated dextran porous microparticles for pulmonary delivery. Mol. Pharm., 2012, 9(2), 290-298. doi: 10.1021/mp2003785 PMID: 22149217
  33. Xi, J. Development and challenges of nasal spray vaccines for short-term COVID-19 protection. Curr. Pharm. Biotechnol., 2022, 23(14), 1671-1677. doi: 10.2174/1389201023666220307092527 PMID: 35255788
  34. Xi, J.; Si, X.A. A next‐generation vaccine for broader and long‐lasting COVID‐19 protection. MedComm, 2022, 3(2), e138. doi: 10.1002/mco2.138 PMID: 35509871
  35. Xi, J.; Lei, L.R.; Zouzas, W.; April Si, X. Nasally inhaled therapeutics and vaccination for COVID‐19: Developments and challenges. MedComm, 2021, 2(4), 569-586. doi: 10.1002/mco2.101 PMID: 34977869
  36. Jabbal-Gill, I. Nasal vaccine innovation. J. Drug Target., 2010, 18(10), 771-786. doi: 10.3109/1061186X.2010.523790 PMID: 21047271
  37. Rahman, M.; Akter, R.; Behl, T.; Chowdhury, M.A.R.; Mohammed, M.; Bulbul, I.J.; Elshenawy, S.E.; Kamal, M.A. COVID-19 outbreak and emerging management through pharmaceutical therapeutic strategy. Curr. Pharm. Des., 2020, 26(41), 5224-5240. doi: 10.2174/18734286MTA4xMTM7z PMID: 32660401
  38. Glezen, W.P. The new nasal spray influenza vaccine. Pediatr. Infect. Dis. J., 2001, 20(8), 731-732. doi: 10.1097/00006454-200108000-00002 PMID: 11734731
  39. Xi, J.; Yuan, J.E.; Zhang, Y.; Nevorski, D.; Wang, Z.; Zhou, Y. Visualization and quantification of nasal and olfactory deposition in a sectional adult nasal airway cast. Pharm. Res., 2016, 33(6), 1527-1541. doi: 10.1007/s11095-016-1896-2 PMID: 26943943
  40. Inthavong, K.; Fung, M.C.; Yang, W.; Tu, J. Measurements of droplet size distribution and analysis of nasal spray atomization from different actuation pressure. J. Aerosol Med. Pulm. Drug Deliv., 2015, 28(1), 59-67. doi: 10.1089/jamp.2013.1093 PMID: 24914675
  41. Cheng, Y.S.; Holmes, T.D.; Gao, J.; Guilmette, R.A.; Li, S.; Surakitbanharn, Y.; Rowlings, C. Characterization of nasal spray pumps and deposition pattern in a replica of the human nasal airway. J. Aerosol Med., 2001, 14(2), 267-280. doi: 10.1089/08942680152484199 PMID: 11681658
  42. Kundoor, V.; Dalby, R.N. Effect of formulation- and administration-related variables on deposition pattern of nasal spray pumps evaluated using a nasal cast. Pharm. Res., 2011, 28(8), 1895-1904. doi: 10.1007/s11095-011-0417-6 PMID: 21499839
  43. Djupesland, P.G. Nasal drug delivery devices: characteristics and performance in a clinical perspective—a review. Drug Deliv. Transl. Res., 2013, 3(1), 42-62. doi: 10.1007/s13346-012-0108-9 PMID: 23316447
  44. Neutra, M.R.; Kozlowski, P.A. Mucosal vaccines: the promise and the challenge. Nat. Rev. Immunol., 2006, 6(2), 148-158. doi: 10.1038/nri1777 PMID: 16491139
  45. Guenezan, J.; Garcia, M.; Strasters, D.; Jousselin, C.; Lévêque, N.; Frasca, D.; Mimoz, O. Povidone Iodine mouthwash, gargle, and nasal spray to reduce nasopharyngeal viral load in patients with COVID-19: a randomized clinical trial. JAMA Otolaryngol. Head Neck Surg., 2021, 147(4), 400-401. doi: 10.1001/jamaoto.2020.5490 PMID: 33538761
  46. Burton, M.J.; Clarkson, J.E.; Goulao, B.; Glenny, A.M.; McBain, A.J.; Schilder, A.G.; Webster, K.E.; Worthington, H.V. Antimicrobial mouthwashes (gargling) and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to improve patient outcomes and to protect healthcare workers treating them. Cochrane Database Syst. Rev., 2020, 9(9), CD013627. PMID: 32936948
  47. Garg, P. Role of povidone-iodine gargles in COVID-19 pandemic and a ray of hope for future. J. Family Med. Prim. Care, 2021, 10(10), 3941-3942. doi: 10.4103/jfmpc.jfmpc_2611_20 PMID: 34934711
  48. Frank, S.; Brown, S.M.; Capriotti, J.A.; Westover, J.B.; Pelletier, J.S.; Tessema, B. In vitro efficacy of a povidone-iodine nasal antiseptic for rapid inactivation of SARS-CoV-2. JAMA Otolaryngol. Head Neck Surg., 2020, 146(11), 1054-1058. doi: 10.1001/jamaoto.2020.3053 PMID: 32940656
  49. Arefin, M.K.; Rumi, S.K.N.F.; Uddin, A.K.M.N.; Banu, S.S.; Khan, M.; Kaiser, A.; Chowdhury, J.A.; Khan, M.A.S.; Hasan, M.J. Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: an open-label randomized clinical trial. Indian J. Otolaryngol. Head Neck Surg., 2022, 74(S2)(Suppl. 2), 2963-2967. doi: 10.1007/s12070-021-02616-7 PMID: 34026595
  50. Frank, S.; Capriotti, J.; Brown, S.M.; Tessema, B. Povidone-Iodine use in sinonasal and oral cavities: a review of safety in the COVID-19 era. Ear Nose Throat J., 2020, 99(9), 586-593. doi: 10.1177/0145561320932318 PMID: 32520599
  51. Zou, L.; Ruan, F.; Huang, M.; Liang, L.; Huang, H.; Hong, Z.; Yu, J.; Kang, M.; Song, Y.; Xia, J.; Guo, Q.; Song, T.; He, J.; Yen, H.L.; Peiris, M.; Wu, J. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N. Engl. J. Med., 2020, 382(12), 1177-1179. doi: 10.1056/NEJMc2001737 PMID: 32074444
  52. Butowt, R.; Bilinska, K. SARS-CoV-2: Olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection. ACS Chem. Neurosci., 2020, 11(9), 1200-1203. doi: 10.1021/acschemneuro.0c00172 PMID: 32283006
  53. Sungnak, W.; Huang, N.; Bécavin, C.; Berg, M.; Queen, R.; Litvinukova, M.; Talavera-López, C.; Maatz, H.; Reichart, D.; Sampaziotis, F.; Worlock, K.B.; Yoshida, M.; Barnes, J.L. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat. Med., 2020, 26(5), 681-687. doi: 10.1038/s41591-020-0868-6 PMID: 32327758
  54. Seifelnasr, A.; Talaat, M.; Ramaswamy, P.; Si, X.A.; Xi, J. A supine position and dual applications enhance spray dosing to posterior nose: paving the way for mucosal immunization. Pharmaceutics, 2023, 15(2), 359. doi: 10.3390/pharmaceutics15020359 PMID: 36839681
  55. Xi, J.; Kim, J.; Si, X.A.; Corley, R.A.; Zhou, Y. Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals. J. Aerosol Sci., 2016, 99, 78-93. doi: 10.1016/j.jaerosci.2016.01.013
  56. Si, X.A.; Sami, M.; Xi, J. Liquid film translocation significantly enhances nasal spray delivery to olfactory region: a numerical simulation study. Pharmaceutics, 2021, 13(6), 903. doi: 10.3390/pharmaceutics13060903 PMID: 34207109
  57. Sung, Y.K.; Kim, S.W. Recent advances in polymeric drug delivery systems. Biomater. Res., 2020, 24(1), 12. doi: 10.1186/s40824-020-00190-7 PMID: 32537239
  58. Mahmood, A.; Patel, D.; Hickson, B.; DesRochers, J.; Hu, X. Recent progress in biopolymer-based hydrogel materials for biomedical applications. Int. J. Mol. Sci., 2022, 23(3), 1415. doi: 10.3390/ijms23031415 PMID: 35163339
  59. Viner, R.M.; Ward, J.L.; Hudson, L.D.; Ashe, M.; Patel, S.V.; Hargreaves, D.; Whittaker, E. Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents. Arch. Dis. Child., 2021, 106(8), 802-807. doi: 10.1136/archdischild-2020-320972 PMID: 33334728
  60. Zare-Zardini, H.; Soltaninejad, H.; Ferdosian, F.; Hamidieh, A.A.; Memarpoor-Yazdi, M. Coronavirus disease 2019 (COVID-19) in children: Prevalence, diagnosis, clinical symptoms, and treatment. Int. J. Gen. Med., 2020, 13, 477-482. doi: 10.2147/IJGM.S262098 PMID: 32848446
  61. Perkušić, M.; Nižić Nodilo, L.; Ugrina, I.; Špoljarić, D.; Jakobušić Brala, C.; Pepić, I.; Lovrić, J.; Safundžić Kučuk, M.; Trenkel, M.; Scherließ, R.; Zadravec, D.; Kalogjera, L.; Hafner, A. Chitosan-based thermogelling system for nose-to-brain donepezil delivery: optimising formulation properties and nasal deposition profile. Pharmaceutics, 2023, 15(6), 1660. doi: 10.3390/pharmaceutics15061660
  62. Rabago, D.; Zgierska, A.; Mundt, M.; Barrett, B.; Bobula, J.; Maberry, R. Efficacy of daily hypertonic saline nasal irrigation among patients with sinusitis: a randomized controlled trial. J. Fam. Pract., 2002, 51(12), 1049-1055. PMID: 12540331
  63. Farrell, N.F.; Klatt-Cromwell, C.; Schneider, J.S. Benefits and safety of nasal saline irrigations in a pandemic—washing COVID-19 away. JAMA Otolaryngol. Head Neck Surg., 2020, 146(9), 787-788. doi: 10.1001/jamaoto.2020.1622 PMID: 32722777
  64. Head, K.; Snidvongs, K.; Glew, S.; Scadding, G.; Schilder, A.G.; Philpott, C.; Hopkins, C. Saline irrigation for allergic rhinitis. Cochrane Database Syst. Rev., 2018, 6(6), CD012597. PMID: 29932206
  65. Si, X.; Xi, J.; Kim, J. Effect of laryngopharyngeal anatomy on expiratory airflow and submicrometer particle deposition in human extrathoracic airways. Open J. Fluid Dyn., 2013, 3(4), 286-301. doi: 10.4236/ojfd.2013.34036
  66. Xi, J.; April Si, X.; Dong, H.; Zhong, H. Effects of glottis motion on airflow and energy expenditure in a human upper airway model. Eur. J. Mech. BFluids, 2018, 72, 23-37. doi: 10.1016/j.euromechflu.2018.04.011
  67. Xi, J.; Yang, T. Variability in oropharyngeal airflow and aerosol deposition due to changing tongue positions. J. Drug Deliv. Sci. Technol., 2019, 49, 674-682. doi: 10.1016/j.jddst.2019.01.006
  68. Mead-Hunter, R.; King, A.J.C.; Larcombe, A.N.; Mullins, B.J. The influence of moving walls on respiratory aerosol deposition modelling. J. Aerosol Sci., 2013, 64, 48-59. doi: 10.1016/j.jaerosci.2013.05.006
  69. Xi, J.; Talaat, M. Nanoparticle deposition in rhythmically moving acinar models with interalveolar septal apertures. Nanomaterials (Basel), 2019, 9(8), 1126. doi: 10.3390/nano9081126 PMID: 31382669
  70. Shang, Y.D.; Inthavong, K.; Tu, J.Y. Detailed micro-particle deposition patterns in the human nasal cavity influenced by the breathing zone. Comput. Fluids, 2015, 114, 141-150. doi: 10.1016/j.compfluid.2015.02.020

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bentham Science Publishers