31
Views
0
CrossRef citations to date
0
Altmetric
Review

Nanomedicines for intranasal delivery: understanding the nano-bio interactions at the nasal mucus-mucosal barrier

, &
Pages 553-572 | Received 04 Jan 2024, Accepted 02 Apr 2024, Published online: 08 May 2024

References

  • Moinuddin S, Razvi S, Uddin MS, et al. Nasal drug delivery system: a innovative approach. Perce. 2019;15:16.
  • Laffleur F, Bauer B. Progress in nasal drug delivery systems. Int J Pharmaceut. 2021;607:120994.
  • Chavda VP, Jogi G, Shah N, et al. Advanced particulate carrier-mediated technologies for nasal drug delivery. J Drug Deli Sci Technol. 2022:103569.
  • Khatri DK, Preeti K, Tonape S, et al. Nanotechnological advances for nose to brain delivery of therapeutics to improve the Parkinson therapy. Current Neuropharmacology. 2023;21:493–516.
  • Das Neves J, Arzi RS, Sosnik A. Molecular and cellular cues governing nanomaterial–mucosae interactions: from nanomedicine to nanotoxicology. Chem Soci Revi. 2020;49:5058–5100.
  • Johansson ME. Fast renewal of the distal colonic mucus layers by the surface goblet cells as measured by in vivo labeling of mucin glycoproteins. PLOS ONE. 2012;7:e41009.
  • Sonvico F, Clementino A, Buttini F, et al. Surface-modified nanocarriers for nose-to-brain delivery: from bioadhesion to targeting. Pharma. 2018;10:34.
  • Fleischer CC, Payne CK. Nanoparticle–cell interactions: molecular structure of the protein corona and cellular outcomes. Acc Chem Res Acco of Chem Rese. 2014;47:2651–2659.
  • Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: sources and toxicity. Bioin. 2007;2:MR17–MR71.
  • Mygind N, Änggård A. Anatomy and physiology of the nose–pathophysiologic alterations in allergic rhinitis. Clin Rev Allergy. 1984;2:173–188.
  • Jeong S, Jang J, Lee Y. Drug delivery to the brain via the nasal route of administration: exploration of key targets and major consideration factors. Jo of Phar Inve. 2023;53:119–152.
  • Pathan N, Shende P. Tailoring of P-glycoprotein for effective transportation of actives across blood-brain-barrier. J Control Release. 2021;335:398–407.
  • Suman, JD. Current understanding of nasal morphology and physiology as a drug delivery target. Drug Deliv Transl Res. 2013;3:4–15.
  • Gizurarson S. The effect of cilia and the mucociliary clearance on successful drug delivery. Biol Pharm Bull. 2015;38:497–506.
  • Netsomboon K, Bernkop-Schnürch A. Mucoadhesive vs. mucopenetrating particulate drug delivery. Eur J Pharm Biopharm. 2016;98:76–89.
  • Bustos NA, Ribbeck K, Wagner CE. The role of mucosal barriers in disease progression and transmission. Adv Drug Delivery Rev. 2023;200:115008.
  • Leal J, Smyth HD, Ghosh D. Physicochemical properties of mucus and their impact on transmucosal drug delivery. Int J Pharmaceut. 2017;532:555–572.
  • Fahy JV, Dickey BF. Airway mucus function and dysfunction. N Engl J Med. 2010;363:2233–2247.
  • Tomazic PV, Birner-Gruenberger R, Leitner A, et al. Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis. J Allergy Clin Immunol. 2014;133:741–750.
  • Sin B, Togias A. Pathophysiology of allergic and nonallergic rhinitis. Proc Am Thorac Soc. 2011;8:106–114.
  • Wagner C, Wheeler K, Ribbeck K. Mucins and their role in shaping the functions of mucus barriers. Annu Rev Cell Dev Biol. 2018;34:189–215.
  • Lieleg O, Ribbeck K. Biological hydrogels as selective diffusion barriers. trends in cell biology. Trends Cell Biol. 2011;21:543–551.
  • Pires PC, Santos AO. Nanosystems in nose-to-brain drug delivery: a review of non-clinical brain targeting studies. J Control Release. 2018;270:89–100.
  • Kočevar-Nared J, Kristl J, Šmid-Korbar J. Comparative rheological investigation of crude gastric mucin and natural gastric mucus. Biomaterials. 1997;18(9):677–681.
  • Dawson M, Krauland E, Wirtz D, et al. Transport of polymeric nanoparticle gene carriers in gastric mucus. Biotechnol Prog. 2004;20:851–857.
  • Formica ML, Real DA, Picchio ML, et al. On a highway to the brain: a review on nose-to-brain drug delivery using nanoparticles. Appl Mater Today. 2022;29:101631.
  • Shah S, Rangaraj N, Singh SB, et al. Exploring the unexplored avenues of surface charge in nano-medicine. Coll Inter Sci Commun. 2021;42:100406.
  • Finbloom JA, Sousa F, Stevens MM, et al. Engineering the drug carrier biointerface to overcome biological barriers to drug delivery. Adv Drug Deli Rev. 2020;167:89–108.
  • Guo Y, Ma Y, Chen X, et al. Mucus penetration of surface-engineered nanoparticles in various pH microenvironments. ACS Nano. 2023;17(3):2813–2828.
  • Kashyap K, Shukla R. Drug delivery and targeting to the brain through nasal route: mechanisms, applications and challenges. Curr Drug Deliv. 2019;16:887–901.
  • McGuckin MB, Wang J, Ghanma R, et al. Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes. J Control Release. 2022;345:334–353.
  • Bala R, Sindhu RK, Kaundle B, et al. The prospective of liquid crystals in nano formulations for drug delivery systems. J Mol Struct. 2021;1245:131117.
  • Wu S, Xia Y, Hu Y, et al. Bio-mimic particles for the enhanced vaccinations: lessons learnt from the natural traits and pathogenic invasion. Adv Drug Deli Rev. 2021;176:113871.
  • Kapate N, Clegg JR, Mitragotri S. Non-spherical micro-and nanoparticles for drug delivery: progress over 15 years. Adv Drug Delivery Rev. 2021;177:113807.
  • Lu X, Miao L, Gao W, et al. Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy. Sci Transl Med. 2020;12(556):eaaz6606.
  • Kumar S, Anselmo AC, Banerjee A, et al. Shape and size-dependent immune response to antigen-carrying nanoparticles. J Control Release. 2015;220:141–148.
  • Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature Biotechnol. 2015;33(9):941–951.
  • Lai SK, Wang Y-Y, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Delivery Rev. 2009;61(2):158–171.
  • Kaliner M, Shelhamer JH, Borson B, et al. Human respiratory mucus. Am Rev Respir Dis. 1986;134:612–621.
  • Bansil R, Turner BS. The biology of mucus: composition, synthesis and organization. Adv Drug Delivery Rev. 2018;124:3–15.
  • Fass D, Thornton DJ. Mucin networks: dynamic structural assemblies controlling mucus function. Curr Opin Struct Biol. 2023;79:102524.
  • McShane A, Bath J, Jaramillo AM, et al. Mucus. Curr Biol. 2021;31:R938–R945.
  • Das Neves J, Sverdlov Arzi R, Sosnik A. Molecular and cellular cues governing nanomaterial-mucosae interactions: from nanomedicine to nanotoxicology. Chem Soc Rev. 2020;49:5058–5100.
  • Das Neves J, Amiji M, Sarmento B. Mucoadhesive nanosystems for vaginal microbicide development: friend or foe? Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2011;3(4):389–399.
  • Puri V, Sharma A, Kumar P, et al. Thiolation of biopolymers for developing drug delivery systems with enhanced mechanical and mucoadhesive properties: a review. Polymers. 2020;12(8):1803.
  • Sellers LA, Allen A, Morris ER, et al. Mucus glycoprotein gels. Role of glycoprotein polymeric structure and carbohydrate side-chains in gel-formation. Carbohydr Res. 1988;178(1):93–110.
  • Liu Z, He H. Synthesis and applications of boronate affinity materials: from class selectivity to biomimetic specificity. Acc Chem Res. 2017;50:2185–2193.
  • Shan X, Aspinall S, Kaldybekov DB, et al. Synthesis and evaluation of methacrylated poly (2-ethyl-2-oxazoline) as a mucoadhesive polymer for nasal drug delivery. ACS Appl Polym Mater. 2021;3:5882–5892.
  • Porfiryeva NN, Nasibullin SF, Abdullina SG, et al. Acrylated Eudragit® E PO as a novel polymeric excipient with enhanced mucoadhesive properties for application in nasal drug delivery. Int J Pharmaceut. 2019;562:241–248.
  • Wang Y-Y, Lai SK, Suk JS, et al. Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that “slip” through the human mucus barrier. Angew Chem Int Ed. 2008;47:9726.
  • McCauley HA, Guasch G. Three cheers for the goblet cell: maintaining homeostasis in mucosal epithelia. Trends Mol Med. 2015;21(8):492–503.
  • Tomazic PV, Darnhofer B, Birner-Gruenberger R. Nasal mucus proteome and its involvement in allergic rhinitis. Expert Rev Proteomics. 2020;17(3):191–199.
  • Tong J, Gu Q. Expression and clinical significance of mucin gene in chronic rhinosinusitis. Curr Allergy Asthma Rep. 2020;20:1–11.
  • Nur Husna SM, Tan H-T-T, Md Shukri N, et al. Nasal epithelial barrier integrity and tight junctions disruption in allergic rhinitis: overview and pathogenic insights. Front Immunol. 2021;12:663626.
  • Brunner J, Ragupathy S, Borchard G. Target specific tight junction modulators. Adv Drug Delivery Rev. 2021;171:266–288.
  • Chegini Z, Noei M, Hemmati J, et al. The destruction of mucosal barriers, epithelial remodeling, and impaired mucociliary clearance: possible pathogenic mechanisms of Pseudomonas aeruginosa and staphylococcus aureus in chronic rhinosinusitis. Cell Commun Signaling. 2023;21(1):306.
  • Elkomy MH, Ali AA, Eid HM. Chitosan on the surface of nanoparticles for enhanced drug delivery: a comprehensive review. J Control Release. 2022;351:923–940.
  • Li M, Zhao M, Fu Y, et al. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra-and paracellular pathways. J Control Release. 2016;228:9–19.
  • Shim S, Yoo HS. The application of mucoadhesive chitosan nanoparticles in nasal drug delivery. Mar Drugs. 2020;18(12):605.
  • Teng Z, Meng L-Y, Yang J-K, et al. Bridging nanoplatform and vaccine delivery, a landscape of strategy to enhance nasal immunity. J Control Release. 2022;351:456–475.
  • Bernocchi B, Carpentier R, Betbeder D. Nasal nanovaccines. Int J Pharmaceut. 2017;530(1–2):128–138.
  • Lim JS, Na HS, Lee HC, et al. Caveolae-mediated entry of salmonella typhimurium in a human M-cell model. Biochem Biophys Res Commun. 2009;390(4):1322–1327.
  • Green BT, Brown DR. Differential effects of clathrin and actin inhibitors on internalization of Escherichia coli and Salmonella choleraesuis in porcine jejunal Peyer’s patches. Vet Microbiol. 2006;113:117–122.
  • Kyd JM, Cripps AW. Functional differences between M cells and enterocytes in sampling luminal antigens. Vaccine. 2008;26(49):6221–6224.
  • Cruz LJ, Rosalia RA, Kleinovink JW, et al. Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8+ T cell response: a comparative study. J Control Release. 2014;192:209–218.
  • Kumar M, Dogra R, Mandal UK. Nanomaterial-based delivery of vaccine through nasal route: opportunities, challenges, advantages, and limitations. J Drug Delivery Sci Technol. 2022;74:103533.
  • Madav Y, Wairkar S. Strategies for enhanced direct nose-to-brain drug delivery. In: Chandrakantsing P, editor. Direct nose-to-brain drug delivery. Amsterdam, Netherlands: Elsevier; 2021. p. 169–184.
  • Akhter MH, Khalilullah H, Gupta M, et al. Impact of protein corona on the biological identity of nanomedicine: understanding the fate of nanomaterials in the biological milieu. Biomedicines. 2021;9(10):1496.
  • Wang X, Zhang W. The Janus of protein corona on nanoparticles for tumor targeting, immunotherapy and diagnosis. J Control Release. 2022;345:832–850.
  • Fasoli E. Protein corona: Dr. Jekyll and Mr. Hyde of nanomedicine. Biotechnol Appl Biochem. 2021;68:1139–1152.
  • Lombardo R, Musumeci T, Carbone C, et al. Nanotechnologies for intranasal drug delivery: an update of literature. Pharm Dev Technol. 2021;26(8):824–845.
  • Digiacomo L, Pozzi D, Palchetti S, et al. Impact of the protein corona on nanomaterial immune response and targeting ability. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2020;12(4):e1615.
  • Wang J, Li Q, Xue J, et al. Shape matters: morphologically biomimetic particles for improved drug delivery. Chem Eng J. 2021;410:127849.
  • Bahng JH, Yeom B, Wang Y, et al. Anomalous dispersions of ‘hedgehog’ particles. Nature. 2015;517(7536):596–599.
  • Fung Y-C. Biomechanics: mechanical properties of living tissues. Media: Springer Science & Business; 2013.
  • Wu L-P, Wang D, Li Z. Grand challenges in nanomedicine. Mater Sci Eng C. 2020;106:110302.
  • Watchorn J, Clasky AJ, Prakash G, et al. Untangling mucosal drug delivery: engineering, designing, and testing nanoparticles to overcome the mucus barrier. ACS Biomater Sci Eng. 2022;8:1396–1426.
  • Marttin E, Schipper NG, Verhoef JC, et al. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Delivery Rev. 1998;29:13–38.
  • Kumar K, Dhawan N, Sharma H, et al. Bioadhesive polymers: novel tool for drug delivery. artificial cells, nanomedicine, and biotechnology. Artific Cells Nanomed Biotechnol. 2014;42(4):274–283.
  • Ugwoke MI, Agu RU, Verbeke N, et al. Nasal mucoadhesive drug delivery: background, applications, trends and future perspectives. Adv Drug Delivery Rev. 2005;57(11):1640–1665.
  • Mackie AR, Goycoolea FM, Menchicchi B, et al. Innovative methods and applications in mucoadhesion research. Macromol biosci. 2017;17:1600534.
  • Robinson TE, Moakes RJ, Grover LM. Low acyl gellan as an excipient to improve the sprayability and mucoadhesion of iota carrageenan in a nasal spray to prevent infection with SARS-CoV-2. Front Med Technol. 2021;3:687681.
  • Freitas AR, Ribeiro AJ, Ribeiro AB, et al. Modification of chicha gum: antibacterial activity, ex vivo mucoadhesion, antioxidant activity and cellular viability. Int j biol macromol. 2023;228:594–603.
  • Alcantara KP, Nalinratana N, Chutiwitoonchai N, et al. Enhanced nasal deposition and anti-coronavirus effect of favipiravir-loaded mucoadhesive chitosan–alginate nanoparticles. Pharmaceutics. 2022;14(12):2680.
  • Vasquez-Martínez N, Guillén D, Moreno-Mendieta SA, et al. In vivo tracing of immunostimulatory raw starch microparticles after mucosal administration. Eur J Pharm Biopharm. 2023;187:96–106. i:
  • Liu S, Yu Q, Guo R, et al. A biodegradable, adhesive, and stretchable hydrogel and potential applications for allergic rhinitis and epistaxis. Adv Healthcare Materials. 2023;12:2302059.
  • Bakhrushina E, Demina N, Krasnyuk I, et al. Development of the composition of the biopolymer base for nasal gel. Drug Res (Stuttg). 2020;70:97–100.
  • Nimi TN, Manohar DR. An overview on in-situ nasal gel for drug delivery. J Pharmaceutical Sci Res. 2019;11:2585–2589.
  • Kurakula M, Rao GK. Pharmaceutical assessment of polyvinylpyrrolidone (PVP): As excipient from conventional to controlled delivery systems with a spotlight on COVID-19 inhibition. J Drug Delivery Sci Technol. 2020;60:102046.
  • Agrawal M, Saraf S, Saraf S, et al. Stimuli-responsive In situ gelling system for nose-to-brain drug delivery. J Control Release. 2020;327:235–265.
  • Abbas Z, Marihal S. Gellan gum-based mucoadhesive microspheres of almotriptan for nasal administration: formulation optimization using factorial design, characterization, and in vitro evaluation. J Pharm Bioallied Sci. 2014;6(4):267.
  • Nathan KG, Genasan K, Kamarul T. Polyvinyl alcohol-chitosan scaffold for tissue engineering and regenerative medicine application: a review. Mar Drugs. 2023;21(5):304.
  • Ito T, Otani N, Fujii K, et al. Bioadhesive and biodissolvable hydrogels consisting of water‐swellable poly (acrylic acid)/poly (vinylpyrrolidone) complexes. J Biomed Mater Res, Part B. 2020;108:503–512.
  • Selvarajah J, Saim AB, Bt Hj Idrus R, et al. Current and alternative therapies for nasal mucosa injury: a review. Int J Mol Sci. 2020;21(2):480.
  • Giradkar P, Patel DH. Vilazodone hydrochloride multi-dose nasal spray solution for the treatment of depression: design, optimization and evaluation. Curr Drug Ther. 2021;16:224–240.
  • Von Zuben EDS, Eloy JO, Inácio MD, et al. Hydroxyethylcellulose-based hydrogels containing liposomes functionalized with cell-penetrating peptides for nasal delivery of insulin in the treatment of diabetes. Pharmaceutics. 2022;14:2492.
  • Trenkel M, Scherließ R. Nasal powder formulations: In-vitro characterisation of the impact of powders on nasal residence time and sensory effects. Pharmaceutics. 2021;13(3):385.
  • Cuggino JC, Blanco ERO, Gugliotta LM, et al. Crossing biological barriers with nanogels to improve drug delivery performance. J Cont Rele. 2019;307:221–246.
  • Pangua C, Reboredo C, Campión R, et al. In Theory and Applications of Nonparenteral Nanomedicines. Amsterdam, Netherlands: Elsevier; 2021; pp. 137–152.
  • Laffleur F, Hintzen F, Shahnaz G, et al. Development and in vitro evaluation of slippery nanoparticles for enhanced diffusion through native mucus. Nanomed. 2014;9:387–396.
  • Nazir I, Leichner C, Le-Vinh B, et al. Surface phosphorylation of nanoparticles by hexokinase: A powerful tool for cellular uptake improvement. Jou Col and int Sci. 2018;516:384–391.
  • Abdulkarim M, Laffleur F, Ramos-Pérez V, et al. Novel Zwitterionic Densely-Charged Neutral Sulfobetaine Nanoparticles for Oral Delivery of Therapeutic Peptides.
  • Shan W, Zhu X, Tao W, et al. Enhanced oral delivery of protein drugs using zwitterion-functionalized nanoparticles to overcome both the diffusion and absorption barriers. . ACS Appd Mat & Int. 2016;8:25444–25453.
  • Yu T, Chan KW, Anonuevo A, et al. Liposome-based mucus-penetrating particles (MPP) for mucosal theranostics: demonstration of diamagnetic chemical exchange saturation transfer (diaCEST) magnetic resonance imaging (MRI). Nanomed: Nanotechn, Bio and Medi. 2015;11:401–405.
  • de Oliveira Junior ER, Santos LCR, Salomão MA, et al. Nose-to-brain drug delivery mediated by polymeric nanoparticles: influence of PEG surface coating. Drug Deli and Trans Res. 2020;10:1688–1699.
  • Mohammadzadeh V, Rahiman N, Cabral H, et al. Poly-γ-glutamic acid nanoparticles as adjuvant and antigen carrier system for cancer vaccination. Jou of Cont Rele. 2023;362:278–296.
  • Ayoubi‐Joshaghani MH, Seidi K, Azizi M, et al. Potential applications of advanced nano/hydrogels in biomedicine: static, dynamic, multi‐stage, and bioinspired. Adv Funct Mat. 2020;30:2004098.
  • Passos M, Dias D, Bastos G, et al. pHEMA hydrogels: Synthesis, kinetics and in vitro tests. Jou Ther Anal and Calori. 2016;125:361–368.
  • Huckaby JT, Lai SK. Pegylation for enhancing nanoparticle diffusion in mucus. Adv Drug Delivery Rev. 2018;124:125–139.
  • Xu Q, Ensign LM, Boylan NJ, et al. Impact of surface polyethylene glycol (PEG) density on biodegradable nanoparticle transport in mucus ex vivo and distribution in vivo. ACS Nano. 2015;9(9):9217–9227.
  • Maisel K, Reddy M, Xu Q, et al. Nanoparticles coated with high molecular weight PEG penetrate mucus and provide uniform vaginal and colorectal distribution in vivo. Nanomedicine. 2016;11(11):1337–1343.
  • Mašek J, Lubasova D, Lukáč R, et al. Multi-layered nanofibrous mucoadhesive films for buccal and sublingual administration of drug-delivery and vaccination nanoparticles-important step towards effective mucosal vaccines. J Control Release. 2017;249:183–195.
  • Taipaleenmäki E, Städler B. Recent advancements in using polymers for intestinal mucoadhesion and mucopenetration. Macromol biosci. 2020;20(3):1900342.
  • Olmsted SS, Padgett JL, Yudin AI, et al. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys J. 2001;81(4):1930–1937.
  • Schattling P, Taipaleenmäki E, Zhang Y, et al. A polymer chemistry point of view on mucoadhesion and mucopenetration. Macro Biosci. 2017;17:1700060.
  • Yang D, Liu D, Qin M, et al. Intestinal mucin induces more endocytosis but less transcytosis of nanoparticles across enterocytes by triggering nanoclustering and strengthening the retrograde pathway. ACS Appl Mater Inter. 2018;10(14):11443–11456.
  • Rohrer J, Partenhauser A, Hauptstein S, et al. Mucus permeating thiolated self-emulsifying drug delivery systems. Euro Jou Pharma Biopharma. 2016;98:90–97.
  • de Sousa IP, Cattoz B, Wilcox MD, et al. Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier. Euro Jou Pharma Biopharma. 2015;97:257–264.
  • Müller C, Leithner K, Hauptstein S, et al. Preparation and characterization of mucus-penetrating papain/poly (acrylic acid) nanoparticles for oral drug delivery applications. Jou Nanopart Res. 2013;15:1–13.
  • Khafagy E-S, Morishita M, Kamei N, et al. Efficiency of cell-penetrating peptides on the nasal and intestinal absorption of therapeutic peptides and proteins. Int J Pharmaceut. 2009;381(1):49–55.
  • Samaridou E, Alonso MJ. Nose-to-brain peptide delivery–the potential of nanotechnology. Bioorg Med Chem. 2018;26(10):2888–2905.
  • Trabulo S, Cardoso AL, Mano M, et al. Cell-penetrating peptides–mechanisms of cellular uptake and generation of delivery systems. Pharmaceuticals. 2010;3:961–993.
  • Derossi D, Calvet S, Trembleau A, et al. Cell internalization of the third helix of the antennapedia homeodomain is receptor-independent. J Biol Chem. 1996;271(30):18188–18193.
  • Ghadiri M, Young PM, Traini D. Strategies to enhance drug absorption via nasal and pulmonary routes. Pharmaceutics. 2019;11(3):113.
  • Na L, Mao S, Wang J, et al. Comparison of different absorption enhancers on the intranasal absorption of isosorbide dinitrate in rats. Int J Pharmaceut. 2010;397(1–2):59–66.
  • Saini H, Rapolu Y, Razdan K, et al. Spanlastics: a novel elastic drug delivery system with potential applications via multifarious routes of administration. J Drug Targeting. 2023;31:999–1012.
  • Ansari MD, Saifi Z, Pandit J, et al. Spanlastics a novel nanovesicular carrier: its potential application and emerging trends in therapeutic delivery. AAPS Pharm Sci Tech. 2022;23(4):112.
  • Alharbi WS, Hareeri RH, Bazuhair M, et al. Spanlastics as a potential platform for enhancing the brain delivery of flibanserin: in vitro response-surface optimization and in vivo pharmacokinetics assessment. Pharmaceutics. 2022;14(12):2627.
  • Fasano A, Not T, Wang W, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000;355(9214):1518–1519.
  • Uchida H, Kondoh M, Hanada T, et al. A claudin-4 modulator enhances the mucosal absorption of a biologically active peptide. Biochem Pharmacol. 2010;79(10):1437–1444.
  • Martins PP, Smyth HD, Cui Z. Strategies to facilitate or block nose-to-brain drug delivery. Int J Pharmaceut. 2019;570:118635.
  • Nguyen T-T-L, Duong V-A, Maeng H-J. Pharmaceutical formulations with P-glycoprotein inhibitory effect as promising approaches for enhancing oral drug absorption and bioavailability. Pharmaceutics. 2021;13:1103.
  • Varma MV, Ashokraj Y, Dey CS, et al. P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement. Pharmacol Res. 2003;48:347–359.
  • Le-Vinh B, Le N-MN, Nazir I, et al. Chitosan based micelle with zeta potential changing property for effective mucosal drug delivery. Int j Biol Macromol. 2019;133:647–655.
  • Bernkop-Schnürch A. Strategies to overcome the polycation dilemma in drug delivery. Adv Drug Deli Rev. 2018;136:62–72.
  • Oh S, Borrós S. Mucoadhesion vs mucus permeability of thiolated chitosan polymers and their resulting nanoparticles using a quartz crystal microbalance with dissipation (QCM-D). Colloids Surf B Biointerfaces. 2016;147:434–441.
  • Bhattacharjee S. DLS and zeta potential–what they are and what they are not? J Control Release. 2016;235:337–351.
  • Di Cola E, Brocca P, Rondelli V, et al. Novel O/W nanoemulsions for nasal administration: structural hints in the selection of performing vehicles with enhanced mucopenetration. Colloids Surf B Biointerfaces. 2019;183:110439.
  • Ways TMM, Filippov SK, Maji S, et al. Mucus-penetrating nanoparticles based on chitosan grafted with various non-ionic polymers: synthesis, structural characterisation and diffusion studies. J Colloid Interface Sci. 2022;626:251–264.
  • Akel H, Csóka I, Ambrus R, et al. In vitro comparative study of solid lipid and PLGA nanoparticles designed to facilitate nose-to-brain delivery of insulin. Int J Mol Sci. 2021;22(24):13258.
  • Sabir F, Katona G, Ismail R, et al. Development and characterization of n-propyl gallate encapsulated solid lipid nanoparticles-loaded hydrogel for intranasal delivery. Pharmaceuticals. 2021;14(7):696.
  • Siddhanta S, Bhattacharjee S, Harrison SM, et al. Shedding light on the trehalose‐enabled mucopermeation of nanoparticles with label‐free raman spectroscopy. Small. 2019;15(33):1901679.
  • Yakubov GE, Singleton S, Williamson AM. Methods for assessing mucoadhesion: the experience of an integrative approach. Mucoadhesive Mat Drug Deli Syst. 2014;2014:197–232.
  • McGlynn JA, Wu N, Schultz KM. Multiple particle tracking microrheological characterization: fundamentals, emerging techniques and applications. J Appl Phys. 2020;127(20):127.
  • Schneider CS, Xu Q, Boylan NJ, et al. Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation. Sci Adv. 2017;3(4):e1601556.
  • Boyuklieva R, Zagorchev P, Pilicheva B. Computational, in vitro, and in vivo models for nose-to-brain drug delivery studies. Biomedicines. 2023;11(8):2198.
  • Haasbroek‐Pheiffer A, Van Niekerk S, Van der Kooy F, et al. In vitro and ex vivo experimental models for evaluation of intranasal systemic drug delivery as well as direct nose‐to‐brain drug delivery. Biopharm Drug Disp. 2023;44:94–112.
  • Volpe DA. Application of method suitability for drug permeability classification. Aaps J. 2010;12(4):670–678.
  • Veronesi MC, Alhamami M, Miedema SB, et al. Imaging of intranasal drug delivery to the brain. Am J Nucl Med Mol Imaging. 2020;10:1.
  • Geva-Zatorsky N, Alvarez D, Hudak JE, et al. In vivo imaging and tracking of host–microbiota interactions via metabolic labeling of gut anaerobic bacteria. Nature Med. 2015;21(9):1091–1100.
  • Hoover EE, Squier JA. Advances in multiphoton microscopy technology. Nat Photonics. 2013;7(2):93–101.
  • Jin C, Ye K, Luan H, et al. Tussilagone inhibits allergic responses in OVA-induced allergic rhinitis guinea pigs and IgE-stimulated RBL-2H3 cells. Fitoterapia. 2020;144:104496.
  • Lux CA, Douglas RG, Cho D-Y, et al. Animal models for inflammatory mucosal disease and their potential for studying the microbiome in chronic rhinosinusitis. Rhinology Online. 2019;2(2):69–80.
  • Emborg ME. Nonhuman primate models of Parkinson’s disease. Ilar J. 2007;48:339–355.
  • Yang M, Lai SK, Wang Y-Y, et al. Biodegradable nanoparticles composed entirely of safe materials that rapidly penetrate human mucus. Angew Chem Int Ed. 2011;50:2597.
  • Das Neves J, Rocha CM, Gonçalves MP, et al. Interactions of microbicide nanoparticles with a simulated vaginal fluid. Mol Pharmaceut. 2012;9:3347–3356.
  • Schömig VJ, Käsdorf BT, Scholz C, et al. An optimized purification process for porcine gastric mucin with preservation of its native functional properties. RSC Adv. 2016;6(50):44932–44943.
  • Larhed AW, Artursson P, Gråsjö J, et al. Diffusion of drugs in native and purified gastrointestinal mucus. J Pharmaceut sci. 1997;86(6):660–665.
  • Dimova S, Brewster M, Noppe M, et al. The use of human nasal in vitro cell systems during drug discovery and development. Toxicol In Vitro. 2005;19(1):107–122.
  • Wengst A, Reichl S. RPMI 2650 epithelial model and three-dimensional reconstructed human nasal mucosa as in vitro models for nasal permeation studies. Eur J Pharm Biopharm. 2010;74(2):290–297.
  • Yang X, Chen X, Lei T, et al. The construction of in vitro nasal cavity-mimic M-cell model, design of M cell-targeting nanoparticles and evaluation of mucosal vaccination by nasal administration. Acta Pharm Sin B. 2020;10(6):1094–1105.
  • Pho T, Champion JA. Surface engineering of protein nanoparticles modulates transport, adsorption, and uptake in mucus. ACS Appl Mater Inter. 2022;14(46):51697–51710.
  • Yip YL, Lin W, Deng W, et al. Establishment of nasopharyngeal carcinoma cell lines, patient-derived xenografts, and immortalized nasopharyngeal epithelial cell lines for nasopharyngeal carcinoma and epstein–barr virus infection studies. In Anne, WM Lee, editors. Nasopharyngeal carcinoma. Amsterdam, Netherlands: Elsevier; 2019. p. 85–107.
  • Forbes B, Shah A, Martin GP, et al. The human bronchial epithelial cell line 16HBE14o–as a model system of the airways for studying drug transport. Int J Pharmaceut. 2003;257(1–2):161–167.
  • Tratnjek L, Sibinovska N, Kristan K, et al. In vitro ciliotoxicity and cytotoxicity testing of repeated chronic exposure to topical nasal formulations for safety studies. Pharmaceutics. 2021;13(11):1750.
  • Ramezanpour M, Smith JL, Psaltis AJ, et al. In vitro safety evaluation of a povidone‐iodine solution applied to human nasal epithelial cells. Int Forum of Alle Rhino. 2020;10:1141–1148.
  • Sousa F, Castro P. Cell-based in vitro models for nasal permeability studies. In: Bruno S, Catarina LP, José DN, editors. Concepts and models for drug permeability studies. Amsterdam, Netherlands: Elsevier; 2016. p. 83–100.
  • Mercier C, Jacqueroux E, He Z, et al. Pharmacological characterization of the 3D MucilAir™ nasal model. Eur J Pharm Biopharm. 2019;139:186–196.
  • Schlachet I, Sosnik A. Mixed mucoadhesive amphiphilic polymeric nanoparticles cross a model of nasal septum epithelium in vitro. ACS Appl Mater Inter. 2019;11(24):21360–21371.
  • Ye D, Dawson KA, Lynch I. A TEM protocol for quality assurance of in vitro cellular barrier models and its application to the assessment of nanoparticle transport mechanisms across barriers. Analyst. 2015;140(1):83–97.
  • Noi I, Schlachet I, Kumarasamy M, et al. Permeability of novel chitosan-g-poly (methyl methacrylate) amphiphilic nanoparticles in a model of small intestine in vitro. Polymers. 2018;10(5):478.
  • Na K, Lee M, Shin H-W, et al. In vitro nasal mucosa gland-like structure formation on a chip. Lab Chip. 2017;17:1578–1584.
  • Usman Khan M, Cai X, Shen Z, et al. Challenges in the development and application of organ-on-chips for intranasal drug delivery studies. Pharmaceutics. 2023;15(5):1557.
  • Bendas S, Koch EV, Nehlsen K, et al. The path from nasal tissue to nasal mucosa on chip: part 1–establishing a nasal in vitro model for drug delivery testing based on a novel cell line. Pharmaceutics. 2023;15(9):2245.
  • Williams G, Suman JD. In vitro anatomical models for nasal drug delivery. Pharmaceutics. 2022;14(7):1353.
  • Alfaifi A, Hosseini S, Esmaeili AR, et al. Anatomically realistic nasal replicas capturing the range of nasal spray drug delivery in adults. Int J Pharmaceut. 2022;622:121858.
  • Deruyver L, Rigaut C, Lambert P, et al. The importance of pre-formulation studies and of 3D-printed nasal casts in the success of a pharmaceutical product intended for nose-to-brain delivery. Adv Drug Delivery Rev. 2021;175:113826.
  • Berben P, Bauer-Brandl A, Brandl M, et al. Drug permeability profiling using cell-free permeation tools: overview and applications. Eur J Pharmaceut Sci. 2018;119:219–233.
  • Furubayashi T, Inoue D, Nishiyama N, et al. Comparison of various cell lines and three-dimensional mucociliary tissue model systems to estimate drug permeability using an in vitro transport study to predict nasal drug absorption in rats. Pharmaceutics. 2020;12(1):79.
  • Fransén N, Espefält Westin U, Nyström C, et al. The in vitro transport of dihydroergotamine across porcine nasal respiratory and olfactory mucosa and the effect of a novel powder formulation. J Drug Delivery Sci Technol. 2007;17(4):267–271.
  • Bartos C, Szabó-Révész P, Horváth T, et al. Comparison of modern in vitro permeability methods with the aim of investigation nasal dosage forms. Pharmaceutics. 2021;13(6):846.
  • Haasbroek-Pheiffer A, Viljoen A, Steenekamp J, et al. An ex vivo investigation on drug permeability of sheep nasal epithelial tissue membranes from the respiratory and olfactory regions. Curr Drug Deliv. 2024;21:115–125.
  • Teng Z, Yang J, Chen X, et al. Intranasal morphology transformation nanomedicines for long-term intervention of allergic rhinitis. ACS Nano. 2023;17(24):25322–25334.
  • Li M, Pan G, Yang Y, et al. Smart aligned multi-layered conductive cryogels with hemostasis and breathability for coagulopathy epistaxis, nasal mucosal repair and bleeding monitoring. Nano Today. 2023;48:101720.
  • Utomo E, Domínguez-Robles J, Moreno-Castellanos N, et al. Development of intranasal implantable devices for schizophrenia treatment. Int J Pharmaceut. 2022;624:122061.
  • Gao X, Xiong Y, Chen H, et al. Mucus adhesion vs. mucus penetration? Screening nanomaterials for nasal inhalation by MD simulation. JControl Release. 2023;353:366–379.
  • Du J, Shao X, Bouteiller J-MC, et al. Computational optimization of delivery parameters to guide the development of targeted nasal spray. Sci Rep. 2023;13:4099.
  • Borthakur MP, Succi S, Sterpone F, et al. In-silico analysis of airflow dynamics and particle transport within a human nasal cavity. J Comput Sci. 2021;54:101411.
  • Feng Y, Zhao J, Hayati H, et al. Tutorial: understanding the transport, deposition, and translocation of particles in human respiratory systems using computational fluid-particle dynamics and physiologically based toxicokinetic models. J Aerosol Sci. 2021;151:105672.
  • Saltzman J, Bendtsen C. Modeling the effect of mucin binding in the gut on drug delivery. Bull Math Biol. 2019;81:3460–3476.
  • Faizal W, Ghazali NNN, Khor C, et al. Computational fluid dynamics modelling of human upper airway: a review. Comput Methods Programs Biomed. 2020;196:105627.
  • Funk J, Hall G, Crandall J, et al. Linear and quasi-linear viscoelastic characterization of ankle ligaments. J Biomech Eng. 2000;122(1):15–22.
  • Sedaghat MH, George UZ, Abouali O. A nonlinear viscoelastic model of mucociliary clearance. Rheol Acta. 2021;60(6–7):371–384.
  • Roy Y, Sivathanu V, Das SK. Effect of bunching of cilia and their interplay on muco-ciliary transport. Comput Biol Med. 2013;43(11):1758–1772.
  • Giesekus H. A simple constitutive equation for polymer fluids based on the concept of deformation-dependent tensorial mobility. J Non-Newtonian Fluid Mech. 1982;11(1–2):69–109.
  • Xu L, Jiang Y. Mathematical modeling of mucociliary clearance: a mini-review. Cells. 2019;8(7):736.
  • Vachhani S, Kleinstreuer C. Comparison of micron-and nano-particle transport in the human nasal cavity with a focus on the olfactory region. Comput Biol Med. 2021;128:104103.
  • Inthavong K, Das P, Singh N, et al. In silico approaches to respiratory nasal flows: A review. J Biomech. 2019;97:109434.
  • Zhao L, Arias SL, Brito IL, et al. Coarse-grained modeling and experimental investigation of the viscoelasticity of human gut mucus and nanoparticle dynamics. bioRxiv. 2023; 2002;2028:530485.
  • Wang J, Shi X. Molecular dynamics simulation of diffusion of nanoparticles in mucus. Acta Mech Solida Sinica. 2017;30(3):241–247.
  • Salo-Ahen OM, Alanko I, Bhadane R, et al. Molecular dynamics simulations in drug discovery and pharmaceutical development. Processes. 2020;9:71.
  • Porfiryeva NN, Semina II, Salakhov IA, et al. Mucoadhesive and mucus-penetrating interpolyelectrolyte complexes for nose-to-brain drug delivery. Nanomedicine. 2021;37:102432.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.