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Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections

Loo et al., Pharmaceutical Research, doi:10.1007/s11095-023-03520-1
Apr 2023  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19hcq.org
Review of nanoformulations for inhaled therapeutics for respiratory viral infections including COVID-19.
Inhaled formulations can deliver treatment directly to the respiratory tract, enabling higher concentrations while minimising systemic side effects, and providing a solution for instability and low solubility issues.
Reviews covering hydroxychloroquine for COVID-19 include Al-Bari, Brouqui, Colson, Derwand, Gao, Goldstein, Hecel, IHU, Kaur, Li, Loo, Matada, Roussel, Sahraei, Scheim, Todaro, Vigbedor.
Review covers ivermectin and HCQ.
Loo et al., 25 Apr 2023, peer-reviewed, 3 authors. Contact: cyloo@unikl.edu.my, tonyzhou@purdue.edu.
This PaperHCQAll
Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections
Ching-Yee Loo, Wing-Hin Lee, Qi Tony Zhou
Pharmaceutical Research, doi:10.1007/s11095-023-03520-1
With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents (e.g. ribavirin, palivizumab and valaciclovir) have been successfully developed for the treatment of respiratory virus infections such as influenza, respiratory syncytial virus and SARS-CoV-2 infections. These therapeutics are conventionally delivered via oral, intramuscular or injection route and are associated with several adverse events due to systemic toxicity. The inherent in vivo instability of biological therapeutics may hinder them from being administered without proper formulations. Therefore, we have witnessed a boom in nanotechnology coupled with a needle-free administration approach such as the inhalation route for the delivery of complex therapeutics to treat respiratory infections. This review discussed the recent advances in the inhalation strategies of nanoformulations that target virus respiratory infections.
Author Contributions Ching-Yee Loo: Substantial contributions to the conception or design of the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published. Wing-Hin Lee: Substantial contributions to the conception or design of the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published. Qi Tony Zhou: Substantial contributions to the conception of the work; revising it critically for important intellectual content; final approval of the version to be published. Declarations Conflict of Interest The authors declare no conflict of interest to this review.
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' 'Virus-like particle vaccine by intranasal vaccination elicits protective ' 'immunity against respiratory syncytial viral infection in mice. Acta ' 'Biochim Biophys Sin (Shanghai). 2017;49(1):74–82.', 'volume': '49', 'year': '2017'}, { 'DOI': '10.1080/21645515.2017.1349584', 'doi-asserted-by': 'crossref', 'key': '3520_CR119', 'unstructured': 'Garg R, Latimer L, Gerdts V, Potter A, van Drunen Littel-van den Hurk S. ' 'Intranasal immunization with a single dose of the fusion protein ' 'formulated with a combination adjuvant induces long-term protective ' 'immunity against respiratory syncytial virus. Hum Vaccin Immunother. ' '2017;13(12):2894–901.'}, { 'DOI': '10.1016/j.virol.2016.09.023', 'doi-asserted-by': 'crossref', 'key': '3520_CR120', 'unstructured': 'Garg R, Theaker M, Martinez EC, van Drunen Littel-van den Hurk S. A ' 'single intranasal immunization with a subunit vaccine formulation ' 'induces higher mucosal IgA production than live respiratory syncytial ' 'virus. Virology. 2016;499:288–97.'}, { 'DOI': '10.1586/14760584.2016.1114418', 'author': 'CJ Russell', 'doi-asserted-by': 'publisher', 'first-page': '189', 'issue': '2', 'journal-title': 'Expert Rev Vaccines', 'key': '3520_CR121', 'unstructured': 'Russell CJ, Hurwitz JL. Sendai virus as a backbone for vaccines against ' 'RSV and other human paramyxoviruses. Expert Rev Vaccines. ' '2016;15(2):189–200.', 'volume': '15', 'year': '2016'}, { 'DOI': '10.1016/j.jpeds.2007.02.032', 'author': 'EA Simoes', 'doi-asserted-by': 'publisher', 'first-page': '34', 'issue': '1', 'journal-title': 'J Pediatr', 'key': '3520_CR122', 'unstructured': 'Simoes EA, Groothuis JR, Carbonell-Estrany X, Rieger CH, Mitchell I, ' 'Fredrick LM, Kimpen JL. Palivizumab prophylaxis, respiratory syncytial ' 'virus, and subsequent recurrent wheezing. J Pediatr. 2007;151(1):34–42, ' '42 e31.', 'volume': '151', 'year': '2007'}, { 'DOI': '10.1016/j.vaccine.2014.03.088', 'author': 'BG Jones', 'doi-asserted-by': 'publisher', 'first-page': '3264', 'issue': '26', 'journal-title': 'Vaccine', 'key': '3520_CR123', 'unstructured': 'Jones BG, Sealy RE, Surman SL, Portner A, Russell CJ, Slobod KS, ' 'Dormitzer PR, DeVincenzo J, Hurwitz JL. Sendai virus-based RSV vaccine ' 'protects against RSV challenge in an in vivo maternal antibody model. ' 'Vaccine. 2014;32(26):3264–73.', 'volume': '32', 'year': '2014'}, { 'DOI': '10.1016/j.vaccine.2011.11.046', 'author': 'BG Jones', 'doi-asserted-by': 'publisher', 'first-page': '959', 'issue': '5', 'journal-title': 'Vaccine', 'key': '3520_CR124', 'unstructured': 'Jones BG, Sealy RE, Rudraraju R, Traina-Dorge VL, Finneyfrock B, Cook A, ' 'Takimoto T, Portner A, Hurwitz JL. Sendai virus-based RSV vaccine ' 'protects African green monkeys from RSV infection. Vaccine. ' '2012;30(5):959–68.', 'volume': '30', 'year': '2012'}, { 'DOI': '10.1128/JVI.74.24.11626-11635.2000', 'author': 'AA Haller', 'doi-asserted-by': 'publisher', 'first-page': '11626', 'issue': '24', 'journal-title': 'J Virol', 'key': '3520_CR125', 'unstructured': 'Haller AA, Miller T, Mitiku M, Coelingh K. Expression of the surface ' 'glycoproteins of human parainfluenza virus type 3 by bovine ' 'parainfluenza virus type 3, a novel attenuated virus vaccine vector. J ' 'Virol. 2000;74(24):11626–35.', 'volume': '74', 'year': '2000'}, { 'DOI': '10.1097/INF.0b013e318199c3b1', 'author': 'M Gomez', 'doi-asserted-by': 'publisher', 'first-page': '655', 'issue': '7', 'journal-title': 'Pediatr Infect Dis J', 'key': '3520_CR126', 'unstructured': 'Gomez M, Mufson MA, Dubovsky F, Knightly C, Zeng W, Losonsky G. Phase-I ' 'study MEDI-534, of a live, attenuated intranasal vaccine against ' 'respiratory syncytial virus and parainfluenza-3 virus in seropositive ' 'children. Pediatr Infect Dis J. 2009;28(7):655–8.', 'volume': '28', 'year': '2009'}, { 'DOI': '10.1097/INF.0b013e31823386f1', 'author': 'DI Bernstein', 'doi-asserted-by': 'publisher', 'first-page': '109', 'issue': '2', 'journal-title': 'Pediatr Infect Dis J', 'key': '3520_CR127', 'unstructured': 'Bernstein DI, Malkin E, Abughali N, Falloon J, Yi T, Dubovsky F. Phase 1 ' 'study of the safety and immunogenicity of a live, attenuated respiratory ' 'syncytial virus and parainfluenza virus type 3 vaccine in seronegative ' 'children. Pediatr Infect Dis J. 2012;31(2):109–14.', 'volume': '31', 'year': '2012'}, { 'DOI': '10.1016/j.vaccine.2013.04.015', 'author': 'CL Nelson', 'doi-asserted-by': 'publisher', 'first-page': '3756', 'issue': '36', 'journal-title': 'Vaccine', 'key': '3520_CR128', 'unstructured': 'Nelson CL, Tang RS, Stillman EA. Genetic stability of RSV-F expression ' 'and the restricted growth phenotype of a live attenuated PIV3 vectored ' 'RSV vaccine candidate (MEDI-534) following restrictive growth in human ' 'lung cells. Vaccine. 2013;31(36):3756–62.', 'volume': '31', 'year': '2013'}, { 'DOI': '10.3389/fimmu.2013.00282', 'author': 'N Van Braeckel-Budimir', 'doi-asserted-by': 'crossref', 'first-page': '282', 'journal-title': 'Front Immunol', 'key': '3520_CR129', 'unstructured': 'Van Braeckel-Budimir N, Haijema BJ, Leenhouts K. Bacterium-like ' 'particles for efficient immune stimulation of existing vaccines and new ' 'subunit vaccines in mucosal applications. Front Immunol. 2013;4:282.', 'volume': '4', 'year': '2013'}, { 'DOI': '10.1164/rccm.201810-1921OC', 'author': 'S Ascough', 'doi-asserted-by': 'publisher', 'first-page': '481', 'issue': '4', 'journal-title': 'Am J Respir Crit Care Med', 'key': '3520_CR130', 'unstructured': 'Ascough S, Vlachantoni I, Kalyan M, Haijema BJ, Wallin-Weber S, ' 'Dijkstra-Tiekstra M, Ahmed MS, van Roosmalen M, Grimaldi R, Zhang Q, ' 'Leenhouts K, Openshaw PJ, Chiu C. Local and Systemic Immunity against ' 'Respiratory Syncytial Virus Induced by a Novel Intranasal Vaccine. A ' 'Randomized, Double-Blind, Placebo-controlled Clinical Trial. Am J Respir ' 'Crit Care Med. 2019;200(4):481–92.', 'volume': '200', 'year': '2019'}, { 'DOI': '10.1016/j.healun.2015.08.012', 'author': 'J Gottlieb', 'doi-asserted-by': 'publisher', 'first-page': '213', 'issue': '2', 'journal-title': 'J Heart Lung Transplant', 'key': '3520_CR131', 'unstructured': 'Gottlieb J, Zamora MR, Hodges T, Musk AW, Sommerwerk U, Dilling D, ' 'Arcasoy S, DeVincenzo J, Karsten V, Shah S, Bettencourt BR, Cehelsky J, ' 'Nochur S, Gollob J, Vaishnaw A, Simon AR, Glanville AR. ALN-RSV01 for ' 'prevention of bronchiolitis obliterans syndrome after respiratory ' 'syncytial virus infection in lung transplant recipients. J Heart Lung ' 'Transplant. 2016;35(2):213–21.', 'volume': '35', 'year': '2016'}, { 'DOI': '10.1016/j.antiviral.2007.11.009', 'author': 'J DeVincenzo', 'doi-asserted-by': 'publisher', 'first-page': '225', 'issue': '3', 'journal-title': 'Antiviral Res', 'key': '3520_CR132', 'unstructured': 'DeVincenzo J, Cehelsky JE, Alvarez R, Elbashir S, Harborth J, Toudjarska ' 'I, Nechev L, Murugaiah V, Van Vliet A, Vaishnaw AK, Meyers R. Evaluation ' 'of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel ' 'RNAi antiviral therapeutic directed against respiratory syncytial virus ' '(RSV). Antiviral Res. 2008;77(3):225–31.', 'volume': '77', 'year': '2008'}, { 'DOI': '10.1164/rccm.201003-0422OC', 'author': 'MR Zamora', 'doi-asserted-by': 'publisher', 'first-page': '531', 'issue': '4', 'journal-title': 'Am J Respir Crit Care Med', 'key': '3520_CR133', 'unstructured': 'Zamora MR, Budev M, Rolfe M, Gottlieb J, Humar A, DeVincenzo J, Vaishnaw ' 'A, Cehelsky J, Albert G, Nochur S, Gollob JA, Glanville AR. RNA ' 'Interference Therapy in Lung Transplant Patients Infected with ' 'Respiratory Syncytial Virus. Am J Respir Crit Care Med. ' '2011;183(4):531–8.', 'volume': '183', 'year': '2011'}, { 'DOI': '10.1093/infdis/jiz408', 'author': 'RA Karron', 'doi-asserted-by': 'publisher', 'first-page': '82', 'issue': '1', 'journal-title': 'J Infect Dis', 'key': '3520_CR134', 'unstructured': 'Karron RA, Luongo C, Mateo JS, Wanionek K, Collins PL, Buchholz UJ. ' 'Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine ' 'RSV/ΔNS2/Δ1313/I1314L in RSV-Seronegative Children. J Infect Dis. ' '2020;222(1):82–91.', 'volume': '222', 'year': '2020'}, { 'DOI': '10.1093/infdis/jiy040', 'author': 'EJ McFarland', 'doi-asserted-by': 'publisher', 'first-page': '1347', 'issue': '9', 'journal-title': 'J Infect Dis', 'key': '3520_CR135', 'unstructured': 'McFarland EJ, Karron RA, Muresan P, Cunningham CK, Valentine ME, ' 'Perlowski C, Thumar B, Gnanashanmugam D, Siberry GK, Schappell E, Barr ' 'E, Rexroad V, Yogev R, Spector SA, Aziz M, Patel N, Cielo M, Luongo C, ' 'Collins PL, Buchholz UJ. Live-Attenuated Respiratory Syncytial Virus ' 'Vaccine Candidate With Deletion of RNA Synthesis Regulatory Protein M2–2 ' 'is Highly Immunogenic in Children. J Infect Dis. 2018;217(9):1347–55.', 'volume': '217', 'year': '2018'}, { 'DOI': '10.1093/infdis/jiz603', 'author': 'EJ McFarland', 'doi-asserted-by': 'publisher', 'first-page': '534', 'issue': '4', 'journal-title': 'J Infect Dis', 'key': '3520_CR136', 'unstructured': 'McFarland EJ, Karron RA, Muresan P, Cunningham CK, Libous J, Perlowski ' 'C, Thumar B, Gnanashanmugam D, Moye J, Schappell E, Barr E, Rexroad V, ' 'Fearn L, Spector SA, Aziz M, Cielo M, Beneri C, Wiznia A, Luongo C, ' 'Collins P, Buchholz UJ. Live Respiratory Syncytial Virus Attenuated by ' 'M2–2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a ' 'Promising Vaccine Candidate in Children. J Infect Dis. ' '2020;221(4):534–43.', 'volume': '221', 'year': '2020'}, { 'DOI': '10.1093/infdis/jiy066', 'author': 'UJ Buchholz', 'doi-asserted-by': 'publisher', 'first-page': '1338', 'issue': '9', 'journal-title': 'J Infect Dis', 'key': '3520_CR137', 'unstructured': 'Buchholz UJ, Cunningham CK, Muresan P, Gnanashanmugam D, Sato P, Siberry ' 'GK, Rexroad V, Valentine M, Perlowski C, Schappell E, Thumar B, Luongo ' 'C, Barr E, Aziz M, Yogev R, Spector SA, Collins PL, McFarland EJ, Karron ' 'RA, International Maternal Pediatric Adolescent ACTPST. Live Respiratory ' 'Syncytial Virus (RSV) Vaccine Candidate Containing Stabilized ' 'Temperature-Sensitivity Mutations Is Highly Attenuated in ' 'RSV-Seronegative Infants and Children. J Infect Dis. ' '2018;217(9):1338–46.', 'volume': '217', 'year': '2018'}, { 'DOI': '10.1126/scitranslmed.aac8463', 'author': 'RA Karron', 'doi-asserted-by': 'publisher', 'first-page': '312ra175', 'issue': '312', 'journal-title': 'Sci Trans Med', 'key': '3520_CR138', 'unstructured': 'Karron RA, Luongo C, Thumar B, Loehr KM, Englund JA, Collins PL, ' 'Buchholz UJ. A gene deletion that up-regulates viral gene expression ' 'yields an attenuated RSV vaccine with improved antibody responses in ' 'children. Sci Trans Med. 2015;7(312):312ra175.', 'volume': '7', 'year': '2015'}, { 'DOI': '10.1093/infdis/jiaa049', 'author': 'EJ McFarland', 'doi-asserted-by': 'publisher', 'first-page': '2050', 'issue': '12', 'journal-title': 'J Infect Dis', 'key': '3520_CR139', 'unstructured': 'McFarland EJ, Karron RA, Muresan P, Cunningham CK, Perlowski C, Libous ' 'J, Oliva J, Jean-Philippe P, Moye J, Schappell E, Barr E, Rexroad V, ' 'Fearn L, Cielo M, Wiznia A, Deville JG, Yang L, Luongo C, Collins PL, ' 'Buchholz UJ. Live-Attenuated Respiratory Syncytial Virus Vaccine With ' 'M2–2 Deletion and With Small Hydrophobic Noncoding Region Is Highly ' 'Immunogenic in Children. J Infect Dis. 2020;221(12):2050–9.', 'volume': '221', 'year': '2020'}, { 'DOI': '10.1136/bmjopen-2015-008748', 'author': 'CA Green', 'doi-asserted-by': 'publisher', 'first-page': 'e008748', 'issue': '10', 'journal-title': 'BMJ Open', 'key': '3520_CR140', 'unstructured': 'Green CA, Scarselli E, Voysey M, Capone S, Vitelli A, Nicosia A, Cortese ' 'R, Thompson AJ, Sande CS, de Lara C, Klenerman P, Pollard AJ. Safety and ' 'immunogenicity of novel respiratory syncytial virus (RSV) vaccines based ' 'on the RSV viral proteins F, N and M2–1 encoded by simian adenovirus ' '(PanAd3-RSV) and MVA (MVA-RSV); protocol for an open-label, ' 'dose-escalation, single-centre, phase 1 clinical trial in healthy ' 'adults. BMJ Open. 2015;5(10):e008748.', 'volume': '5', 'year': '2015'}, { 'DOI': '10.1126/scitranslmed.aac5745', 'author': 'CA Green', 'doi-asserted-by': 'publisher', 'first-page': '300ra126', 'issue': '300', 'journal-title': 'Sci Trans Med', 'key': '3520_CR141', 'unstructured': 'Green CA, Scarselli E, Sande CJ, Thompson AJ, de Lara CM, Taylor KS, ' 'Haworth K, Del Sorbo M, Angus B, Siani L, Di Marco S, Traboni C, Folgori ' 'A, Colloca S, Capone S, Vitelli A, Cortese R, Klenerman P, Nicosia A, ' 'Pollard AJ. Chimpanzee adenovirus- and MVA-vectored respiratory ' 'syncytial virus vaccine is safe and immunogenic in adults. Sci Trans ' 'Med. 2015;7(300):300ra126.', 'volume': '7', 'year': '2015'}, { 'DOI': '10.1016/j.jinf.2019.02.003', 'author': 'CA Green', 'doi-asserted-by': 'publisher', 'first-page': '382', 'issue': '5', 'journal-title': 'J Infect', 'key': '3520_CR142', 'unstructured': 'Green CA, Sande CJ, Scarselli E, Capone S, Vitelli A, Nicosia A, ' 'Silva-Reyes L, Thompson AJ, de Lara CM, Taylor KS, Haworth K, Hutchings ' 'CL, Cargill T, Angus B, Klenerman P, Pollard AJ. Novel ' 'genetically-modified chimpanzee adenovirus and MVA-vectored respiratory ' 'syncytial virus vaccine safely boosts humoral and cellular immunity in ' 'healthy older adults. J Infect. 2019;78(5):382–92.', 'volume': '78', 'year': '2019'}, { 'DOI': '10.1124/dmd.122.000934', 'author': 'ER McColl', 'doi-asserted-by': 'publisher', 'first-page': '130', 'issue': '1', 'journal-title': 'Drug Metab Dispos', 'key': '3520_CR143', 'unstructured': 'McColl ER, Croyle MA, Zamboni WC, Honer WG, Heise M, Piquette-Miller M, ' 'Goralski KB. COVID-19 Vaccines and the Virus: Impact on Drug Metabolism ' 'and Pharmacokinetics. Drug Metab Dispos. 2023;51(1):130–41.', 'volume': '51', 'year': '2023'}], 'reference-count': 143, 'references-count': 143, 'relation': {}, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s11095-023-03520-1'}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': [ 'Pharmacology (medical)', 'Organic Chemistry', 'Pharmaceutical Science', 'Pharmacology', 'Molecular Medicine', 'Biotechnology'], 'subtitle': [], 'title': 'Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory ' 'Viral Infections', 'type': 'journal-article', 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy'}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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