Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Amr Seifelnasr, Mohamed Talaat, Xiuhua April Si and Jinxiang Xi*

Volume 25, Issue 6, 2024

Published on: 18 August, 2023

Page: [787 - 798] Pages: 12

DOI: 10.2174/1389201024666230801142913

Price: $65

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.

Results: 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.

« Previous
Graphical Abstract

[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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1002/mco2.101] [PMID: 34977869]
[36]
Jabbal-Gill, I. Nasal vaccine innovation. J. Drug Target., 2010, 18(10), 771-786.
[http://dx.doi.org/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.
[http://dx.doi.org/10.2174/18734286MTA4xMTM7z] [PMID: 32660401]
[38]
Glezen, W.P. The new nasal spray influenza vaccine. Pediatr. Infect. Dis. J., 2001, 20(8), 731-732.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1016/j.compfluid.2015.02.020]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy