Abstract
Biologics are a rapidly emerging class of therapeutics that have succeeded clinically and commercially due to their specificity and efficacy against various diseases including cancer, inflammatory, and autoimmune diseases. Even though most biologics are administered parenterally, nasal and pulmonary delivery would be beneficial due to numerous advantages such as being patient-friendly, noninvasive, cost-effective, and less toxic. While there are currently a few nasal and inhaled biologics on the market, for example, Suprefact®, Minirin®, Miacalcin®, most of them are designed to treat ailments related to prostate carcinoma, diabetes, osteoporosis but not for respiratory diseases. Moreover, there are some marketed nasally delivered vaccines such as Flumist® and Nasovac-S® against influenza virus, inhaled vaccines that did not make it to market. Given the rise of respiratory infections such as MERS, SARS, and SARS-CoV-2, a great deal of interest exists in developing nasal and pulmonary-delivered biologics and vaccines for respiratory diseases. The objective of this chapter is to describe the potential for pulmonary and nasal delivery of biologics. Each section delves into introducing biologics and vaccines, followed by a portrayal of recent updates on nasal and pulmonary delivery of biologics and vaccines. The most promising formulation strategies for enhancing the stability and therapeutic efficacy of biologics as a part of research and development will be discussed.
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Notes
- 1.
Biologics, biological products, biotherapeutics, biological medicines, biopharmaceutical products are the terms used interchangeably even though there are some minor differences.
References
Agarwal R, Johnson CT, Imhoff BR, Donlan RM, McCarty NA, García AJ (2018) Inhaled bacteriophage-loaded polymeric microparticles ameliorate acute lung infections. Nat Biomed Eng 2(11):841–849. https://doi.org/10.1038/s41551-018-0263-5
Agu RU, Ugwoke MI, Armand M, Kinget R, Verbeke N (2001) The lung as a route for systemic delivery of therapeutic proteins and peptides. Respir Res 2(4):198–209. https://doi.org/10.1186/rr58
Al-Tabakha MM (2015) Future prospect of insulin inhalation for diabetic patients: the case of Afrezza versus Exubera. J Control Release 215:25–38. https://doi.org/10.1016/j.jconrel.2015.07.025
Amelina E, Krasovskiy S, Abdulganieva D, Asherova I, Zilber I, Trishina S, Kozyreva L, Kudelya L, Magnitskaya O, Ponomareva N, Revel-Muroz N, Reutskaya E, Stepanenko T, Fadeeva T, Seitova G, Uhanova O (2020) Efficacy and safety of the biosimilar medicinal product Tigerase® (dornase alfa) in long-term symptomatic treatment of patients with cystic fibrosis: results of a phase III clinical trial. Russian Pulmonol 29:695–706. https://doi.org/10.18093/0869-0189-2019-29-6-695-706
Anselmo AC, Gokarn Y, Mitragotri S (2019) Non-invasive delivery strategies for biologics. Nat Rev Drug Discov 18(1):19–40. https://doi.org/10.1038/nrd.2018.183
Antosova Z, Mackova M, Kral V, Macek T (2009) Therapeutic application of peptides and proteins: parenteral forever? Trends Biotechnol 27(11):628–635. https://doi.org/10.1016/j.tibtech.2009.07.009
Arias-Pinilla GA, Dalgleish AG, Mudan S, Bagwan I, Walker AJ, Modjtahedi H (2020) Development and application of two novel monoclonal antibodies against overexpressed CD26 and integrin α3 in human pancreatic cancer. Sci Rep 10(1):537. https://doi.org/10.1038/s41598-019-57287-w
Arrowsmith S, Wray S (2014) Oxytocin: its mechanism of action and receptor signalling in the myometrium. J Neuroendocrinol 26(6):356–369. https://doi.org/10.1111/jne.12154
Azizi A, Kumar A, Diaz-Mitoma F, Mestecky J (2010) Enhancing Oral vaccine potency by targeting intestinal M cells. PLoS Pathog 6:e1001147. https://doi.org/10.1371/journal.ppat.1001147
Bahamondez-Canas TF, Cui Z (2018) Intranasal immunization with dry powder vaccines. Eur J Pharm Biopharm 122:167–175. https://doi.org/10.1016/j.ejpb.2017.11.001
Bailey CJ, Barnett AH (2007) Why is Exubera being withdrawn? BMJ 335(7630):1156–1156. https://doi.org/10.1136/bmj.39409.507662.94
Bajracharya R, Song JG, Back SY, Han H-K (2019) Recent advancements in non-invasive formulations for protein drug delivery. Comput Struct Biotechnol J 17:1290–1308. https://doi.org/10.1016/j.csbj.2019.09.004
Beck-Broichsitter M (2019) Making concentrated antibody formulations accessible for vibrating-mesh nebulization. J Pharm Sci 108(8):2588–2592. https://doi.org/10.1016/j.xphs.2019.03.009
Bernasconi V, Norling K, Bally M, Höök F, Lycke NY (2016) Mucosal vaccine development based on liposome technology. J Immunol Res 2016:5482087. https://doi.org/10.1155/2016/5482087
Bigelow AM, Ghanayem NS, Thompson NE, Scott JP, Cassidy LD, Woods KJ, Woods RK, Mitchell ME, Hraŝka V, Hoffman GM (2019) Safety and efficacy of vasopressin after Fontan completion: a randomized pilot study. Ann Thorac Surg 108(6):1865–1874. https://doi.org/10.1016/j.athoracsur.2019.06.053
Bivas-Benita M, van Meijgaarden KE, Franken KLMC, Junginger HE, Borchard G, Ottenhoff THM, Geluk A (2004) Pulmonary delivery of chitosan-DNA nanoparticles enhances the immunogenicity of a DNA vaccine encoding HLA-A*0201-restricted T-cell epitopes of Mycobacterium tuberculosis. Vaccine 22(13):1609–1615. https://doi.org/10.1016/j.vaccine.2003.09.044
Blank F, Stumbles P, von Garnier C (2011) Opportunities and challenges of the pulmonary route for vaccination. Expert Opin Drug Deliv 8(5):547–563. https://doi.org/10.1517/17425247.2011.565326
Bodier-Montagutelli E, Mayor A, Vecellio L, Respaud R, Heuzé-Vourc’h N (2018) Designing inhaled protein therapeutics for topical lung delivery: what are the next steps? Expert Opin Drug Deliv 15(8):729–736. https://doi.org/10.1080/17425247.2018.1503251
Boehncke W-H, Brembilla NC (2018) Immunogenicity of biologic therapies: causes and consequences. Expert Rev Clin Immunol 14(6):513–523. https://doi.org/10.1080/1744666X.2018.1468753
Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL (2002) Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 5(6):514–516. https://doi.org/10.1038/nn0602-849
Brandström J, Vetander M, Sundqvist AC, Lilja G, Johansson SGO, Melén E, Sverremark-Ekström E, Nopp A, Nilsson C (2019) Individually dosed omalizumab facilitates peanut oral immunotherapy in peanut allergic adolescents. Clin Exp Allergy 49(10):1328–1341. https://doi.org/10.1111/cea.13469
Bruyn S, Smedt T, Allosery K, Crabbe P, De Brabandere V, Detalle L, Mortier K, Schoolmeester A, Wouters H, Stöhr T (2015) Depla E (2015) ALX-0171: safety and therapeutic potential of an inhaled anti-RSV Nanobody. RDD Europe 1:37–48
Burgess G, Boyce M, Jones M, Larsson L, Main MJ, Morgan F, Phillips P, Scrimgeour A, Strimenopoulou F, Vajjah P, Zamacona M, Palframan R (2018) Randomized study of the safety and pharmacodynamics of inhaled interleukin-13 monoclonal antibody fragment VR942. EBioMedicine 35:67–75. https://doi.org/10.1016/j.ebiom.2018.07.035
Carvalho AL, Fonseca S, Miquel-Clopés A, Cross K, Kok K-S, Wegmann U, Gil-Cardoso K, Bentley EG, Al Katy SHM, Coombes JL, Kipar A, Stentz R, Stewart JP, Carding SR (2019) Bioengineering commensal bacteria-derived outer membrane vesicles for delivery of biologics to the gastrointestinal and respiratory tract. J Extracell Vesicl 8(1):1632100. https://doi.org/10.1080/20013078.2019.1632100
Chan JCN, Chan ATC (2017) Biologics and biosimilars: what, why and how? ESMO Open 2(1):e000180. https://doi.org/10.1136/esmoopen-2017-000180
Chang RYK, Wallin M, Lin Y, Leung SSY, Wang H, Morales S, Chan HK (2018) Phage therapy for respiratory infections. Adv Drug Deliv Rev 133:76–86. https://doi.org/10.1016/j.addr.2018.08.001
Chang RYK, Kwok PCL, Khanal D, Morales S, Kutter E, Li J, Chan HK (2020) Inhalable bacteriophage powders: glass transition temperature and bioactivity stabilization. Bioeng Transl Med 5(2):e10159. https://doi.org/10.1002/btm2.10159
Chung SW, Al-Hilal T, Byun Y (2012) Strategies for non-invasive delivery of biologics. J Drug Target 20:481–501. https://doi.org/10.3109/1061186X.2012.693499
Cipolla DC, Gonda I (2011) Formulation technology to repurpose drugs for inhalation delivery. Drug Discov Today Therap Strat 8(3):123–130. https://doi.org/10.1016/j.ddstr.2011.07.001
Coates AL (2008) Guiding aerosol deposition in the lung. N Engl J Med 358(3):304–305. https://doi.org/10.1056/NEJMcibr0707489
Cohen S, Alonso MJ, Langer R (1994) Novel approaches to controlled-release antigen delivery. Int J Technol Assess Health Care 10(1):121–130. https://doi.org/10.1017/s0266462300014045
Colombo RE, Fiorentino C, Dodd LE, Hunsberger S, Haney C, Barrett K, Nabha L, Davey RT Jr, Olivier KN (2016) A phase 1 randomized, double-blind, placebo-controlled, crossover trial of DAS181 (Fludase®) in adult subjects with well-controlled asthma. BMC Infect Dis 16(1):54. https://doi.org/10.1186/s12879-016-1358-9
Cruz E, Kayser V (2020) Major classes of biotherapeutics. In: Ramzan I (ed) Biologics, biosimilars, and biobetters. https://doi.org/10.1002/9781119564690.ch4
D’Souza MJ, Gala RP, Ubale RV, D’Souza B, Vo TP, Parenky AC, Mulla NS, D’Sa S, D’Souza M, Braz-Gomes K, D’Souza N, Chiriva-Internati M, Zughaier S (2015) Chapter 5 - Trends in nonparenteral delivery of biologics, vaccines and Cancer therapies. In: Singh M, Salnikova M (eds) Novel approaches and strategies for biologics, vaccines and cancer therapies. Academic Press, San Diego, CA, pp 89–122. https://doi.org/10.1016/B978-0-12-416603-5.00005-5
Dabbagh A, Abu Kasim NH, Yeong CH, Wong TW, Abdul Rahman N (2018) Critical parameters for particle-based pulmonary delivery of chemotherapeutics. J Aerosol Med Pulm Drug Del 31(3):139–154. https://doi.org/10.1089/jamp.2017.1382
Dhakal S, Cheng X, Salcido J, Renu S, Bondra K, Lakshmanappa YS, Misch C, Ghimire S, Feliciano-Ruiz N, Hogshead B, Krakowka S, Carson K, McDonough J, Lee CW, Renukaradhya GJ (2018a) Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs. Int J Nanomedicine 13:6699–6715. https://doi.org/10.2147/ijn.S178809
Dhakal S, Renu S, Ghimire S, Shaan Lakshmanappa Y, Hogshead BT, Feliciano-Ruiz N, Lu F, HogenEsch H, Krakowka S, Lee CW, Renukaradhya GJ (2018b) Mucosal immunity and protective efficacy of intranasal inactivated influenza vaccine is improved by chitosan nanoparticle delivery in pigs. Front Immunol 9:934. https://doi.org/10.3389/fimmu.2018.00934
Díaz Ortega JL, Castaneda D, Arellano Quintanilla DM, Martínez D, Trumbo SP, Fernández de Castro J (2017) Antibody persistence in children aged 6–7years one year following booster immunization with two MMR vaccines applied by aerosol or by injection. Vaccine 35(23):3116–3122. https://doi.org/10.1016/j.vaccine.2017.04.027
Diaz KT, Skaria S, Harris K, Solomita M, Lau S, Bauer K, Smaldone GC, Condos R (2012) Delivery and safety of inhaled interferon-γ in idiopathic pulmonary fibrosis. J Aerosol Med Pulm Drug Deliv 25(2):79–87. https://doi.org/10.1089/jamp.2011.0919
Díaz-Ortega JL, Bennett JV, Castañeda D, Martinez D, Fernandez de Castro J (2010) Antibody persistence in young adults 1 year after MMR immunization by aerosol or by subcutaneous route. Vaccine 28(44):7228–7232. https://doi.org/10.1016/j.vaccine.2010.08.055
Dilraj A, Sukhoo R, Cutts FT, Bennett JV (2007) Aerosol and subcutaneous measles vaccine: measles antibody responses 6 years after re-vaccination. Vaccine 25(21):4170–4174. https://doi.org/10.1016/j.vaccine.2007.03.003
Earhart AP, Holliday ZM, Hofmann HV, Schrum AG (2020) Consideration of dornase alfa for the treatment of severe COVID-19 acute respiratory distress syndrome. New Microbes New Infect 35:100689. https://doi.org/10.1016/j.nmni.2020.100689
Ehrick JD, Shah SA, Shaw C, Kulkarni VS, Coowanitwong I, De S, Suman JD (2013) Considerations for the development of nasal dosage forms. Sterile Prod Dev 6:99–144. https://doi.org/10.1007/978-1-4614-7978-9_5
Fellner RC, Terryah ST, Tarran R (2016) Inhaled protein/peptide-based therapies for respiratory disease. Mol Cell Pediatr 3(1):16–16. https://doi.org/10.1186/s40348-016-0044-8
Feng CG, Demangel C, Kamath AT, Macdonald M, Britton WJ (2001) Dendritic cells infected with Mycobacterium bovis bacillus Calmette Guerin activate CD8+ T cells with specificity for a novel mycobacterial epitope. Int Immunol 13(4):451–458. https://doi.org/10.1093/intimm/13.4.451
Florindo HF, Kleiner R, Vaskovich-Koubi D, Acúrcio RC, Carreira B, Yeini E, Tiram G, Liubomirski Y, Satchi-Fainaro R (2020) Immune-mediated approaches against COVID-19. Nat Nanotechnol. https://doi.org/10.1038/s41565-020-0732-3
Garg H, Mehmetoglu-Gurbuz T, Joshi A (2020) Virus like particles (VLP) as multivalent vaccine candidate against chikungunya, Japanese encephalitis, yellow fever and Zika virus. Sci Rep 10(1):4017. https://doi.org/10.1038/s41598-020-61103-1
Ghadiri M, Young PM, Traini D (2019) Strategies to enhance drug absorption via nasal and pulmonary routes. Pharmaceutics 11(3):113. https://doi.org/10.3390/pharmaceutics11030113
Gharse S, Fiegel J (2016) Large porous hollow particles: lightweight champions of pulmonary drug delivery. Curr Pharm Des 22(17):2463–2469. https://doi.org/10.2174/1381612822666160128145356
Gibson E, Begum N, Martinón-Torres F, Safadi MA, Sackeyfio A, Hackett J, Rajaram S (2016) Cost-effectiveness analysis of the direct and indirect impact of intranasal live attenuated influenza vaccination strategies in children: alternative country profiles. J Mark Access Health Policy 4:31205. https://doi.org/10.3402/jmahp.v4.31205
Gomes dos Reis L, Traini D (2020) Advances in the use of cell penetrating peptides for respiratory drug delivery. Expert Opin Drug Deliv 17(5):647–664. https://doi.org/10.1080/17425247.2020.1739646
Griffin DE (2014) Current progress in pulmonary delivery of measles vaccine. Expert Rev Vaccines 13(6):751–759. https://doi.org/10.1586/14760584.2014.915753
Griffiths KL, Ahmed M, Das S, Gopal R, Horne W, Connell TD, Moynihan KD, Kolls JK, Irvine DJ, Artyomov MN, Rangel-Moreno J, Khader SA (2016) Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy. Nat Commun 7(1):13894. https://doi.org/10.1038/ncomms13894
Hajos F, Stark B, Hensler S, Prassl R, Mosgoeller W (2008) Inhalable liposomal formulation for vasoactive intestinal peptide. Int J Pharm 357(1):286–294. https://doi.org/10.1016/j.ijpharm.2008.01.046
Han J, Zhao D, Li D, Wang X, Jin Z, Zhao K (2018) Polymer-based nanomaterials and applications for vaccines and drugs. Polymers (Basel) 10(1):31. https://doi.org/10.3390/polym10010031
Hiremath GS, Omer SB (2005) A meta-analysis of studies comparing the respiratory route with the subcutaneous route of measles vaccine administration. Hum Vaccin 1(1):30–36. https://doi.org/10.4161/hv.1.1.1423
Holland MC, Wurthner JU, Morley PJ, Birchler MA, Lambert J, Albayaty M, Serone AP, Wilson R, Chen Y, Forrest RM, Cordy JC, Lipson DA, Bayliffe AI (2013) Autoantibodies to variable heavy (VH) chain Ig sequences in humans impact the safety and clinical pharmacology of a VH domain antibody antagonist of TNF-α receptor 1. J Clin Immunol 33(7):1192–1203. https://doi.org/10.1007/s10875-013-9915-0
Huang YY, Wang CH (2006) Pulmonary delivery of insulin by liposomal carriers. J Control Release 113(1):9–14. https://doi.org/10.1016/j.jconrel.2006.03.014
Illum L, Jordan F, Lewis A (2012) CriticalSorb (TM): a novel efficient nasal delivery system for human growth hormone based on Solutol HS15. J Controll Rel 162:194–200. https://doi.org/10.1016/j.jconrel.2012.06.014
Influenza Vaccine for 2019–2020 (2019) Med Lett Drugs Ther 61(1583):161–166
Influenza vaccine for 2020-2021 (2020) Med Lett Drugs Ther 62(1607):145–150
Introduction to Biologics and Monoclonal Antibodies (2012) In: Strohl WR, Strohl LM (eds) Therapeutic antibody engineering. Woodhead Publishing, pp 1–595. https://doi.org/10.1533/9781908818096.1
Irvine DJ, Su X, Kwong B (2013) Routes of delivery for biological drug products. In: Pharmaceutical sciences encyclopedia, pp 1–48. https://doi.org/10.1002/9780470571224.pse521
Jiao YY, Fu YH, Yan YF, Hua Y, Ma Y, Zhang XJ, Song JD, Peng XL, Huang J, Hong T, He JS (2017) A single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus. Antivir Res 144:57–69. https://doi.org/10.1016/j.antiviral.2017.05.005
Joshi M, Nagarsenkar M, Prabhakar B (2020) Albumin nanocarriers for pulmonary drug delivery: an attractive approach. J Drug Deliv Sci Technol 56. https://doi.org/10.1016/j.jddst.2020.101529
Kanojia G, Have RT, Soema PC, Frijlink H, Amorij J-P, Kersten G (2017) Developments in the formulation and delivery of spray dried vaccines. Hum Vaccin Immunother 13(10):2364–2378. https://doi.org/10.1080/21645515.2017.1356952
Kanojia G, Raeven RHM, van der Maas L, Bindels THE, van Riet E, Metz B, Soema PC, ten Have R, Frijlink HW, Amorij J-P, Kersten GFA (2018) Development of a thermostable spray dried outer membrane vesicle pertussis vaccine for pulmonary immunization. J Control Release 286:167–178. https://doi.org/10.1016/j.jconrel.2018.07.035
Kashangura R, Jullien S, Garner P, Johnson S (2019) MVA85A vaccine to enhance BCG for preventing tuberculosis. Cochrane Database Syst Rev 4(4):CD012915–CD012915. https://doi.org/10.1002/14651858.CD012915.pub2
Kayser V, Reslan M (2020) Pivotal biology, chemistry, biochemistry, and biophysical concepts of biologics and biosimilars. In: Ramzan I (ed) Biologics, biosimilars, and biobetters. https://doi.org/10.1002/9781119564690.ch6
Kayser V, Sen M (2020) New emerging biotherapies. In: Ramzan I (ed) Biologics, biosimilars, and biobetters. https://doi.org/10.1002/9781119564690.ch13
Kilgore PE, Salim AM, Zervos MJ, Schmitt H-J (2016) Pertussis: microbiology, disease, treatment, and prevention. Clin Microbiol Rev 29(3):449–486. https://doi.org/10.1128/CMR.00083-15
Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI (2019) Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov 18(8):585–608. https://doi.org/10.1038/s41573-019-0028-1
Lee Y-T, Ko E-J, Lee Y, Kim K-H, Kim M-C, Lee Y-N, Kang S-M (2018) Intranasal vaccination with M2e5x virus-like particles induces humoral and cellular immune responses conferring cross-protection against heterosubtypic influenza viruses. PLoS One 13(1):e0190868. https://doi.org/10.1371/journal.pone.0190868
Liu Y, Li S, Lin W, Li W, Yan X, Wang X, Pan X, Rutledge RB, Ma Y (2019) Oxytocin modulates social value representations in the amygdala. Nat Neurosci 22(4):633–641. https://doi.org/10.1038/s41593-019-0351-1
Lu R-M, Hwang Y-C, Liu IJ, Lee C-C, Tsai H-Z, Li H-J, Wu H-C (2020) Development of therapeutic antibodies for the treatment of diseases. J Biomed Sci 27(1):1. https://doi.org/10.1186/s12929-019-0592-z
Macleod M (2018) Learning lessons from MVA85A, a failed booster vaccine for BCG. BMJ 360:k66. https://doi.org/10.1136/bmj.k66
Mahajan PB (2016) Recent advances in application of pharmacogenomics for biotherapeutics. AAPS J 18(3):605–611. https://doi.org/10.1208/s12248-016-9903-4
Mallick P, Taneja G, Moorthy B, Ghose R (2017) Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics-small molecule drug interactions. Expert Opin Drug Metab Toxicol 13(6):605–616. https://doi.org/10.1080/17425255.2017.1292251
Manjaly Thomas Z-R, Satti I, Marshall JL, Harris SA, Lopez Ramon R, Hamidi A, Minhinnick A, Riste M, Stockdale L, Lawrie AM, Vermaak S, Wilkie M, Bettinson H, McShane H (2019) Alternate aerosol and systemic immunisation with a recombinant viral vector for tuberculosis, MVA85A: a phase I randomised controlled trial. PLoS Med 16(4):e1002790. https://doi.org/10.1371/journal.pmed.1002790
Marqus S, Pirogova E, Piva T (2017) Evaluation of the use of therapeutic peptides for cancer treatment. J Biomed Sci 24. https://doi.org/10.1186/s12929-017-0328-x
McCarthy MW, Kockler DR (2004) Trivalent intranasal influenza vaccine, live. Ann Pharmacother 38(12):2086–2093. https://doi.org/10.1345/aph.1E191
Menon JU, Ravikumar P, Pise A, Gyawali D, Hsia CCW, Nguyen KT (2014) Polymeric nanoparticles for pulmonary protein and DNA delivery. Acta Biomater 10(6):2643–2652. https://doi.org/10.1016/j.actbio.2014.01.033
Mócsai A, Kovács L, Gergely P (2014) What is the future of targeted therapy in rheumatology: biologics or small molecules? BMC Med 12:43. https://doi.org/10.1186/1741-7015-12-43
Mohanty RR, Das S (2017) Inhaled insulin - current direction of insulin research. J Clin Diagn Res 11(4):OE01–OE02. https://doi.org/10.7860/JCDR/2017/23626.9732
Mohsen MO, Zha L, Cabral-Miranda G, Bachmann MF (2017) Major findings and recent advances in virus-like particle (VLP)-based vaccines. Semin Immunol 34:123–132. https://doi.org/10.1016/j.smim.2017.08.014
Monteiro N, Martins A, Reis RL, Neves NM (2014) Liposomes in tissue engineering and regenerative medicine. J R Soc Interface 11(101):20140459–20140459. https://doi.org/10.1098/rsif.2014.0459
Morales JO, Fathe KR, Brunaugh A, Ferrati S, Li S, Montenegro-Nicolini M, Mousavikhamene Z, McConville JT, Prausnitz MR, Smyth HDC (2017) Challenges and future prospects for the delivery of biologics: oral mucosal, pulmonary, and transdermal routes. AAPS J 19(3):652–668. https://doi.org/10.1208/s12248-017-0054-z
Morris JK, Burns JM (2012) Insulin: an emerging treatment for Alzheimer’s disease dementia? Curr Neurol Neurosci Rep 12(5):520–527. https://doi.org/10.1007/s11910-012-0297-0
Morrow T, Felcone LH (2004) Defining the difference: what makes biologics unique. Biotechnol Healthc 1(4):24–29
Moschos SA, Jones SW, Perry MM, Williams AE, Erjefalt JS, Turner JJ, Barnes PJ, Sproat BS, Gait MJ, Lindsay MA (2007) Lung delivery studies using siRNA conjugated to TAT(48−60) and Penetratin reveal peptide induced reduction in gene expression and induction of innate immunity. Bioconjug Chem 18(5):1450–1459. https://doi.org/10.1021/bc070077d
Moscona A, Porotto M, Palmer S, Tai C, Aschenbrenner L, Triana-Baltzer G, Li Q-X, Wurtman D, Niewiesk S, Fang F (2010) A recombinant sialidase fusion protein effectively inhibits human parainfluenza viral infection in vitro and in vivo. J Infect Dis 202(2):234–241. https://doi.org/10.1086/653621
Moyer TJ, Zmolek AC, Irvine DJ (2016) Beyond antigens and adjuvants: formulating future vaccines. J Clin Invest 126(3):799–808. https://doi.org/10.1172/JCI81083
Nagpal PS, Kesarwani A, Sahu P, Upadhyay P (2019) Aerosol immunization by alginate coated mycobacterium (BCG/MIP) particles provide enhanced immune response and protective efficacy than aerosol of plain mycobacterium against M.tb. H37Rv infection in mice. BMC Infect Dis 19(1):568. https://doi.org/10.1186/s12879-019-4157-2
Naskalska A, Dabrowska A, Nowak P, Szczepanski A, Jasik K, Milewska A, Ochman M, Zeglen S, Rajfur Z, Pyrc K (2018) Novel coronavirus-like particles targeting cells lining the respiratory tract. PLoS One 13(9):e0203489. https://doi.org/10.1371/journal.pone.0203489
New RRC (2019) Formulation technologies for oral vaccines. Clin Exp Immunol 198(2):153–169. https://doi.org/10.1111/cei.13352
Nicholls JM, Moss RB, Haslam SM (2013) The use of sialidase therapy for respiratory viral infections. Antivir Res 98(3):401–409. https://doi.org/10.1016/j.antiviral.2013.04.012
Nigwekar PV, Kumar A, Padbidri VV, Choudhury A, Chaudhari AB, Kulkarni PS (2018) Safety of Russian-backbone trivalent, live attenuated seasonal influenza vaccine in healthy subjects: open-label, non-randomized phase 4 study. Drug Saf 41(2):171–177. https://doi.org/10.1007/s40264-017-0605-3
Nisini R, Poerio N, Mariotti S, De Santis F, Fraziano M (2018) The multirole of liposomes in therapy and prevention of infectious diseases. Front Immunol 9(155). https://doi.org/10.3389/fimmu.2018.00155
Nongkhlaw R, Patra P, Chavrasiya A, Jayabalan N, Dubey S (2020) Chapter 6 - Biologics: delivery options and formulation strategies. In: Shegokar R (ed) Drug delivery aspects. Elsevier, pp 115–155. https://doi.org/10.1016/B978-0-12-821222-6.00006-3
Osman N, Kaneko K, Carini V, Saleem I (2018) Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies. Expert Opin Drug Deliv 15(8):821–834. https://doi.org/10.1080/17425247.2018.1502267
Ozsoy Y, Gungor S, Cevher E (2009) Nasal delivery of high molecular weight drugs. Molecules 14(9):3754–3779. https://doi.org/10.3390/molecules14093754
Patton JS, Byron PR (2007) Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 6(1):67–74. https://doi.org/10.1038/nrd2153
Proudfoot A, Bayliffe A, O’Kane CM, Wright T, Serone A, Bareille PJ, Brown V, Hamid UI, Chen Y, Wilson R, Cordy J, Morley P, de Wildt R, Elborn S, Hind M, Chilvers ER, Griffiths M, Summers C, McAuley DF (2018) Novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury. Thorax 73(8):723. https://doi.org/10.1136/thoraxjnl-2017-210305
Qosa H, Volpe DA (2018) The development of biological therapies for neurological diseases: moving on from previous failures. Expert Opin Drug Discovery 13(4):283–293. https://doi.org/10.1080/17460441.2018.1437142
Rader RA (2008) (re)defining biopharmaceutical. Nat Biotechnol 26(7):743–751. https://doi.org/10.1038/nbt0708-743
Rahhal TB, Fromen CA, Wilson EM, Kai MP, Shen TW, Luft JC, DeSimone JM (2016) Pulmonary delivery of Butyrylcholinesterase as a model protein to the lung. Mol Pharm 13(5):1626–1635. https://doi.org/10.1021/acs.molpharmaceut.6b00066
Ramvikas M, Arumugam M, Chakrabarti SR, Jaganathan KS (2017) Nasal vaccine delivery. Micro Nanotechnol Vacc Dev:279–301. https://doi.org/10.1016/B978-0-323-39981-4.00015-4
Reslan M, Demir YK, Trout BL, Chan HK, Kayser V (2017) Lack of a synergistic effect of arginine-glutamic acid on the physical stability of spray-dried bovine serum albumin. Pharm Dev Technol 22(6):785–791. https://doi.org/10.1080/10837450.2016.1185116
Reslan M, Ranganathan V, Macfarlane DR, Kayser V (2018) Choline ionic liquid enhances the stability of Herceptin® (trastuzumab). Chem Commun 54(75):10622–10625. https://doi.org/10.1039/C8CC06397D
Respaud R, Marchand D, Parent C, Pelat T, Thullier P, Tournamille J-F, Viaud-Massuard M-C, Diot P, Si-Tahar M, Vecellio L, Heuzé-Vourc’h N (2014) Effect of formulation on the stability and aerosol performance of a nebulized antibody. MAbs 6(5):1347–1355. https://doi.org/10.4161/mabs.29938
Respaud R, Vecellio L, Diot P, Heuzé-Vourc’h N (2015) Nebulization as a delivery method for mAbs in respiratory diseases. Expert Opin Drug Deliv 12(6):1027–1039. https://doi.org/10.1517/17425247.2015.999039
Rohrer J, Lupo N, Bernkop-Schnürch A (2018) Advanced formulations for intranasal delivery of biologics. Int J Pharm 553(1):8–20. https://doi.org/10.1016/j.ijpharm.2018.10.029
Rombach-Riegraf V, Karle AC, Wolf B, Sordé L, Koepke S, Gottlieb S, Krieg J, Djidja M-C, Baban A, Spindeldreher S, Koulov AV, Kiessling A (2014) Aggregation of human recombinant monoclonal antibodies influences the capacity of dendritic cells to stimulate adaptive T-cell responses in vitro. PLoS One 9(1):e86322. https://doi.org/10.1371/journal.pone.0086322
Rosales-Mendoza S, González-Ortega O (2019) Virus-like particles-based mucosal nanovaccines. In: Nanovaccines. Springer, Cham, pp 267–318. https://doi.org/10.1007/978-3-030-31668-6_10
Salvatore M, Satlin MJ, Jacobs SE, Jenkins SG, Schuetz AN, Moss RB, Van Besien K, Shore T, Soave R (2016) DAS181 for treatment of parainfluenza virus infections in hematopoietic stem cell transplant recipients at a single center. Biol Blood Marrow Transplant 22(5):965–970. https://doi.org/10.1016/j.bbmt.2016.02.011
Satti I, Meyer J, Harris SA, Manjaly Thomas ZR, Griffiths K, Antrobus RD, Rowland R, Ramon RL, Smith M, Sheehan S, Bettinson H, McShane H (2014) Safety and immunogenicity of a candidate tuberculosis vaccine MVA85A delivered by aerosol in BCG-vaccinated healthy adults: a phase 1, double-blind, randomised controlled trial. Lancet Infect Dis 14(10):939–946. https://doi.org/10.1016/s1473-3099(14)70845-x
Schiffter HA (2011) The delivery of drugs – peptides and proteins. 5:587–604. https://doi.org/10.1016/B978-0-08-088504-9.00338-X
Schwartzman LM, Cathcart AL, Pujanauski LM, Qi L, Kash JC, Taubenberger JK (2015) An intranasal virus-like particle vaccine broadly protects mice from multiple subtypes of influenza a virus. mBio 6(4):e01044–e01015. https://doi.org/10.1128/mBio.01044-15
Sécher T, Dalonneau E, Ferreira M, Parent C, Azzopardi N, Paintaud G, Si-Tahar M, Heuzé-Vourc’H N (2019) In a murine model of acute lung infection, airway administration of a therapeutic antibody confers greater protection than parenteral administration. J Control Release 303:24–33. https://doi.org/10.1016/j.jconrel.2019.04.005
Serno T, Carpenter JF, Randolph TW, Winter G (2010) Inhibition of agitation-induced aggregation of an IgG-antibody by hydroxypropyl-beta-cyclodextrin. J Pharm Sci 99(3):1193–1206. https://doi.org/10.1002/jps.21931
Shakya AK, Nandakumar KS (2013) Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases. J R Soc Interface 10(79):20120536–20120536. https://doi.org/10.1098/rsif.2012.0536
Shen C, Gao Y, Li J, Du H, Liang R, Sun Y, Xie J, Dong L, Zhang Y, Zhu J, Zhang B, Shen G, Chen X, Zhu J, Tao J (2020) Intrinsic Adjuvanticity of branched Polyethylenimine in vitro and subcutaneously. ACS Appl Polym Mater 2(4):1438–1447. https://doi.org/10.1021/acsapm.9b01016
Shoyele SA, Sivadas N, Cryan S-A (2011) The effects of excipients and particle engineering on the biophysical stability and aerosol performance of parathyroid hormone (1-34) prepared as a dry powder for inhalation. AAPS PharmSciTech 12(1):304–311. https://doi.org/10.1208/s12249-011-9585-2
Skalko-Basnet N (2014) Biologics: the role of delivery systems in improved therapy. Biologics 8:107–114. https://doi.org/10.2147/BTT.S38387
Steeland S, Libert C, Vandenbroucke RE (2018) A New venue of TNF targeting. Int J Mol Sci 19(5). https://doi.org/10.3390/ijms19051442
Su F, Patel GB, Hu S, Chen W (2016) Induction of mucosal immunity through systemic immunization: phantom or reality? Hum Vaccin Immunother 12(4):1070–1079. https://doi.org/10.1080/21645515.2015.1114195
Talbot HK, Nian H, Zhu Y, Chen Q, Williams JV, Griffin MR (2015) Clinical effectiveness of split-virion versus subunit trivalent influenza vaccines in older adults. Clin Infect Dis 60(8):1170–1175. https://doi.org/10.1093/cid/civ019
Tambuyzer E, Vandendriessche B, Austin CP, Brooks PJ, Larsson K, Miller Needleman KI, Valentine J, Davies K, Groft SC, Preti R, Oprea TI, Prunotto M (2020) Therapies for rare diseases: therapeutic modalities, progress and challenges ahead. Nat Rev Drug Discov 19(2):93–111. https://doi.org/10.1038/s41573-019-0049-9
Thakur A, Rodríguez-Rodríguez C, Saatchi K, Rose F, Esposito T, Nosrati Z, Andersen P, Christensen D, Häfeli UO, Foged C (2018) Dual-isotope SPECT/CT imaging of the tuberculosis subunit vaccine H56/CAF01: induction of strong systemic and mucosal IgA and T-cell responses in mice upon subcutaneous prime and intrapulmonary boost immunization. Front Immunol 9(2825). https://doi.org/10.3389/fimmu.2018.02825
Tonnis WF, Lexmond AJ, Frijlink HW, de Boer AH, Hinrichs WL (2013) Devices and formulations for pulmonary vaccination. Expert Opin Drug Deliv 10(10):1383–1397. https://doi.org/10.1517/17425247.2013.810622
Tsao C, Yuan Z, Zhang P, Liu E, McMullen P, Wu K, Hung HC, Jiang S (2020) Enhanced pulmonary systemic delivery of protein drugs via zwitterionic polymer conjugation. J Control Release 322:170–176. https://doi.org/10.1016/j.jconrel.2020.03.019
Van Heeke G, Allosery K, De Brabandere V, De Smedt T, Detalle L, de Fougerolles A (2017) Nanobodies®††Nanobody is a registered trademark of Ablynx NV. As inhaled biotherapeutics for lung diseases. Pharmacol Ther 169:47–56. https://doi.org/10.1016/j.pharmthera.2016.06.012
van Rijt SH, Bein T, Meiners S (2014) Medical nanoparticles for next generation drug delivery to the lungs. Eur Respir J 44(3):765–774. https://doi.org/10.1183/09031936.00212813
Végh A (1987) Experiences with Kryptocur in the treatment of cryptorchism. Acta Chir Hung 28(4):257–261
Vela Ramirez JE, Sharpe LA, Peppas NA (2017) Current state and challenges in developing oral vaccines. Adv Drug Deliv Rev 114:116–131. https://doi.org/10.1016/j.addr.2017.04.008
Vu TN, Chen X, Foda HD, Smaldone GC, Hasaneen NA (2019) Interferon-γ enhances the antifibrotic effects of pirfenidone by attenuating IPF lung fibroblast activation and differentiation. Respir Res 20(1):206. https://doi.org/10.1186/s12931-019-1171-2
Vulto AG, Jaquez OA (2017) The process defines the product: what really matters in biosimilar design and production? Rheumatology (Oxford) 56(suppl_4):iv14–iv29. https://doi.org/10.1093/rheumatology/kex278
Wacker D, Ludwig M (2019) The role of vasopressin in olfactory and visual processing. Cell Tissue Res 375(1):201–215. https://doi.org/10.1007/s00441-018-2867-1
Wang N, Wei C, Zhang Z, Liu T, Wang T (2020) Aluminum nanoparticles acting as a pulmonary vaccine adjuvant-delivery system (VADS) able to safely elicit robust systemic and mucosal immunity. J Inorg Organomet Polym Mater. https://doi.org/10.1007/s10904-020-01572-z
Wilson EM, Luft JC, DeSimone JM (2018) Formulation of high-performance dry powder aerosols for pulmonary protein delivery. Pharm Res 35(10):195. https://doi.org/10.1007/s11095-018-2452-z
Xie X, Gao L, Shull A, Teng Y (2016) Stapled peptides: Providing the best of both worlds in drug development. Fut Med Chem:8. https://doi.org/10.4155/fmc-2016-0102
Xu J, Wong DHC, Byrne JD, Chen K, Bowerman C, DeSimone JM (2013) Future of the particle replication in nonwetting templates (PRINT) technology. Angew Chem Int Ed Engl 52(26):6580–6589. https://doi.org/10.1002/anie.201209145
Zaman M, Chandrudu S, Toth I (2013) Strategies for intranasal delivery of vaccines. Drug Deliv Transl Res 3(1):100–109. https://doi.org/10.1007/s13346-012-0085-z
Zelikin AN, Ehrhardt C, Healy AM (2016) Materials and methods for delivery of biological drugs. Nat Chem 8(11):997–1007. https://doi.org/10.1038/nchem.2629
Zhao L, T-h R, Wang DD (2012) Clinical pharmacology considerations in biologics development. Acta Pharmacol Sin 33(11):1339–1347. https://doi.org/10.1038/aps.2012.51
Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair C, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS (2020) Neutrophil extracellular traps in COVID-19. JCI Insight 5(11). https://doi.org/10.1172/jci.insight.138999
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Komalla, V., Haghi, M., Kayser, V. (2022). Biologics and Vaccines for Nasal and Pulmonary Drug Delivery. In: Chellappan, D.K., Pabreja, K., Faiyazuddin, M. (eds) Advanced Drug Delivery Strategies for Targeting Chronic Inflammatory Lung Diseases . Springer, Singapore. https://doi.org/10.1007/978-981-16-4392-7_21
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