Utilization of endogenous albumin trafficking pathways in the lungs has potential to modestly increase the lung interstitial access and absorption of drug delivery systems after inhaled administration

References

• Patton JS, Byron PR. Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov. 2007 Jan;6(1):67–74. doi: 10.1038/nrd2153
   PubMed Web of Science ®Google Scholar
• Patton JS, Fishburn CS, Weers JG. The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc. 2004;1(4):338–344. doi: 10.1513/pats.200409-049TA
   PubMedGoogle Scholar
• Reed MD. Optimal antibiotic dosing. The pharmacokinetic-pharmacodynamic interface. Postgrad Med. 2000 Dec;108(7 Suppl Contemporaty):17–24. doi: 10.3810/pgm.12.2000.suppl10.52
   PubMedGoogle Scholar
• Haque S, Whittaker MR, McIntosh MP, et al. Disposition and safety of inhaled biodegradable nanomedicines: opportunities and challenges. Nanomedicine. 2016 Aug;12(6):1703–1724. doi: 10.1016/j.nano.2016.03.002
   PubMed Web of Science ®Google Scholar
• Sakai N, Tager AM. Fibrosis of two: epithelial cell-fibroblast interactions in pulmonary fibrosis. Biochim Biophys Acta. 2013 Jul;1832(7):911–921. doi: 10.1016/j.bbadis.2013.03.001
   PubMed Web of Science ®Google Scholar
• Kumar A, Mantri SN. Lymphangitic Carcinomatosis. [Updated 2022 Sep 19]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. https://www.ncbi.nlm.nih.gov/books/NBK560921/
   Google Scholar
• Tiruppathi C, Song W, Bergenfeldt M, et al. Gp60 activation mediates albumin transcytosis in endothelial cells by tyrosine kinase-dependent pathway. J Biol Chem. 1997 Oct 10;272(41):25968–25975. doi: 10.1074/jbc.272.41.25968
   PubMed Web of Science ®Google Scholar
• van der Deen M, de Vries EG, Timens W, et al. ATP-binding cassette (ABC) transporters in normal and pathological lung. Respir Res. 2005 Jun 20;6(1):59.
   PubMedGoogle Scholar
• Neves J, Haider T, Gassmann M, et al. Iron homeostasis in the lungs-A balance between health and disease. Pharmaceuticals (Basel). 2019 Jan 1;12(1). doi: 10.3390/ph12010005
   Google Scholar
• Kratz F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Release. 2008 Dec 18;132(3):171–183. doi: 10.1016/j.jconrel.2008.05.010
   PubMed Web of Science ®Google Scholar
• Berthiaume Y, Albertine KH, Grady M, et al. Protein clearance from the air spaces and lungs of unanesthetized sheep over 144 h. J Appl Physiol (1985). 1989 Nov;67(5):1887–1897. doi: 10.1152/jappl.1989.67.5.1887
   PubMed Web of Science ®Google Scholar
• Kim KJ, Malik AB. Protein transport across the lung epithelial barrier. Am J Physiol Lung Cell Mol Physiol. 2003 Feb;284(2):L247–59. doi: 10.1152/ajplung.00235.2002
   PubMed Web of Science ®Google Scholar
• Karami E, Behdani M, Kazemi-Lomedasht F. Albumin nanoparticles as nanocarriers for drug delivery: Focusing on antibody and nanobody delivery and albumin-based drugs. J Drug Deliv Sci Tec. 2020 Feb 55;55:101471. doi: 10.1016/j.jddst.2019.101471
   Web of Science ®Google Scholar
• Joshi M, Nagarsenkar M, Prabhakar B. Albumin nanocarriers for pulmonary drug delivery: an attractive approach. J Drug Deliv Sci Tec. 2020 Apr 56;56:101529. doi: 10.1016/j.jddst.2020.101529
   Web of Science ®Google Scholar
• Huang YF, Upton RN, Runciman WB, et al. Insight into interstitial drug disposition: lymph concentrations of lidocaine, procainamide and meperidine in the hindquarters of unanesthetized and anesthetized sheep. J Pharmacol Exp Ther. 1991 Jan;256(1):69–75.
   PubMed Web of Science ®Google Scholar
• Wiig H, Swartz MA. Interstitial fluid and lymph formation and transport: physiological regulation and roles in inflammation and cancer. Physiol Rev. 2012 Jul;92(3):1005–1060. doi: 10.1152/physrev.00037.2011
   PubMed Web of Science ®Google Scholar
• Rutili G, Arfors KE. Protein concentration in interstitial and lymphatic fluids from the subcutaneous tissue. Acta Physiol Scand. 1977 Jan;99(1):1–8. doi: 10.1111/j.1748-1716.1977.tb10345.x
   PubMedGoogle Scholar
• Ryan GM, Bischof RJ, Enkhbaatar P, et al. A comparison of the pharmacokinetics and pulmonary lymphatic exposure of a generation 4 Pegylated dendrimer following intravenous and aerosol administration to rats and sheep. Pharm Res. 2016 Feb;33(2):510–525. doi: 10.1007/s11095-015-1806-z
   PubMed Web of Science ®Google Scholar
• Driscoll KE, Costa DL, Hatch G, et al. Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. Toxicol Sci. 2000 May;55(1):24–35. doi: 10.1093/toxsci/55.1.24
   PubMed Web of Science ®Google Scholar
• Kuehn A, Kletting S, de Souza Carvalho-Wodarz C, et al. Human alveolar epithelial cells expressing tight junctions to model the air-blood barrier. ALTEX. 2016;33(3):251–260. doi: 10.14573/altex.1511131
   PubMedGoogle Scholar
• Ibrahim JP, Haque S, Bischof RJ, et al. Liposomes are poorly absorbed via lung lymph after inhaled administration in sheep. Front Pharmacol. 2022;13:880448. doi: 10.3389/fphar.2022.880448
   PubMed Web of Science ®Google Scholar
• Bujacz A, Talaj JA, Zielinski K, et al. Crystal structures of serum albumins from domesticated ruminants and their complexes with 3,5-diiodosalicylic acid. Acta Crystallogr D Struct Biol. 2017 Nov;73(11):896–909. doi: 10.1107/S205979831701470X
   PubMedGoogle Scholar
• Kaminskas LM, Landersdorfer CB, Bischof RJ, et al. Aerosol pirfenidone pharmacokinetics after inhaled delivery in sheep: a viable approach to treating idiopathic pulmonary fibrosis. Pharm Res. 2019 Dec 10;37(1):3.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Huo M, Zhou J, et al. Pksolver: an add-in program for pharmacokinetic and pharmacodynamic data analysis in microsoft excel. Comput Methods Programs Biomed. 2010 Sep;99(3):306–314. doi: 10.1016/j.cmpb.2010.01.007
   PubMed Web of Science ®Google Scholar
• Taylor AE, Gaar KA. Estimation of equivalent pore radii of pulmonary capillary and alveolar membranes. Am J Physiol. 1970;218(4):1133–&. doi: 10.1152/ajplegacy.1970.218.4.1133
   PubMedGoogle Scholar
• Meyer EC, Ottaviano R, Higgins JJ. Albumin clearance from alveoli: tissue permeation vs. airway displacement. J Appl Physiol Respir Environ Exerc Physiol. 1977 Sep;43(3):487–497. doi: 10.1152/jappl.1977.43.3.487
   PubMed Web of Science ®Google Scholar
• Buchackert Y, Rummel S, Vohwinkel CU, et al. Megalin mediates transepithelial albumin clearance from the alveolar space of intact rabbit lungs. J Physiol. 2012 Oct 15;590(20):5167–5181.
   PubMed Web of Science ®Google Scholar
• Kim KJ, Matsukawa Y, Yamahara H, et al. Absorption of intact albumin across rat alveolar epithelial cell monolayers. Am J Physiol Lung Cell Mol Physiol. 2003 Mar;284(3):L458–65. doi: 10.1152/ajplung.00237.2002
   PubMed Web of Science ®Google Scholar
• Schnitzer JE. Gp60 is an albumin-binding glycoprotein expressed by continuous endothelium involved in albumin transcytosis. Am J Physiol. 1992 Jan;262(1 Pt 2):H246–54. doi: 10.1152/ajpheart.1992.262.1.H246
   PubMed Web of Science ®Google Scholar
• Tiruppathi C, Finnegan A, Malik AB. Isolation and characterization of a cell surface albumin-binding protein from vascular endothelial cells. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):250–254.
   PubMed Web of Science ®Google Scholar
• Li HH, Li J, Wasserloos KJ, et al. Caveolae-dependent and -independent uptake of albumin in cultured rodent pulmonary endothelial cells. Plos One. 2013;8(11):e81903. doi: 10.1371/journal.pone.0081903
   PubMed Web of Science ®Google Scholar
• Vogel SM, Minshall RD, Pilipovic M, et al. Albumin uptake and transcytosis in endothelial cells in vivo induced by albumin-binding protein. Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1512–22. doi: 10.1152/ajplung.2001.281.6.L1512
   PubMed Web of Science ®Google Scholar
• John TA, Vogel SM, Minshall RD, et al. Evidence for the role of alveolar epithelial gp60 in active transalveolar albumin transport in the rat lung. J Physiol. 2001 Jun 1;533(Pt 2):547–559.
   PubMed Web of Science ®Google Scholar
• John TA, Vogel SM, Minshall RD, et al. Evidence for the role of alveolar epithelial gp60 in active transalveolar albumin transport in the rat lung. J Physiol-London. 2001 Jun 1;533(2):547–559.
   PubMed Web of Science ®Google Scholar
• Rennard SI, Basset G, Lecossier D, et al. Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. J Appl Physiol (1R985). 1986 Feb;60(2):532–538.
   PubMed Web of Science ®Google Scholar
• Mackie WS, Fell BF. The half-life of serum albumin in relation to liver hypertrophy in the lactating ewe. Res Vet Sci. 1971 Jan;12(1):54–58. doi: 10.1016/S0034-5288(18)34238-3
   PubMed Web of Science ®Google Scholar
• Chaudhury C, Mehnaz S, Robinson JM, et al. The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J Exp Med. 2003 Feb 3;197(3):315–322. doi: 10.1084/jem.20021829
   PubMed Web of Science ®Google Scholar
• Andersen JT, Dalhus B, Cameron J, et al. Structure-based mutagenesis reveals the albumin-binding site of the neonatal Fc receptor. Nat Commun. 2012 Jan 3;3(1):610.
   PubMedGoogle Scholar
• Walker KW, Salimi-Moosavi H, Arnold GE, et al. Pharmacokinetic comparison of a diverse panel of non-targeting human antibodies as matched IgG1 and IgG2 isotypes in rodents and non-human primates. Plos One. 2019;14(5):e0217061. doi: 10.1371/journal.pone.0217061
   PubMed Web of Science ®Google Scholar
• Abdiche YN, Yeung YA, Chaparro-Riggers J, et al. The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity. MAbs. 2015;7(2):331–343. doi: 10.1080/19420862.2015.1008353
   PubMed Web of Science ®Google Scholar
• Andersen JT, Daba MB, Berntzen G, et al. Cross-species binding analyses of mouse and human neonatal Fc receptor show dramatic differences in immunoglobulin G and albumin binding. J Biol Chem. 2010 Feb 12;285(7):4826–4836.
   PubMed Web of Science ®Google Scholar
• Kuilamu E, Subasic C, Cowin GJ, et al. Cetuximab exhibits sex differences in lymphatic exposure after intravenous administration in rats in the absence of differences in plasma exposure. Pharm Res. 2020 Oct 19;37(11):224.
   PubMed Web of Science ®Google Scholar
• Li C, Marton I, Harari D, et al. Gelatin stabilizes nebulized proteins in pulmonary drug delivery against COVID-19. ACS Biomater Sci Eng. 2022 Jun 13;8(6):2553–2563.
   PubMed Web of Science ®Google Scholar
• Schultz AL, Grismer JT, Wada S, et al. Absorption of albumin from alveoli of perfused dog lung. Am J Physiol. 1964 Dec;207(6):1300–1304. doi: 10.1152/ajplegacy.1964.207.6.1300
   PubMedGoogle Scholar
• Trevaskis NL, Kaminskas LM, Porter CJ. From sewer to saviour - targeting the lymphatic system to promote drug exposure and activity. Nat Rev Drug Discov. 2015 Nov;14(11):781–803. doi: 10.1038/nrd4608
   PubMed Web of Science ®Google Scholar
• Furuyama A, Kanno S, Kobayashi T, et al. Extrapulmonary translocation of intratracheally instilled fine and ultrafine particles via direct and alveolar macrophage-associated routes. Arch Toxicol. 2009 May;83(5):429–437. doi: 10.1007/s00204-008-0371-1
   PubMed Web of Science ®Google Scholar
• Choi HS, Ashitate Y, Lee JH, et al. Rapid translocation of nanoparticles from the lung airspaces to the body. Nat Biotechnol. 2010 Dec;28(12):1300–1303. doi: 10.1038/nbt.1696
   PubMed Web of Science ®Google Scholar
• Wang YB, Watts AB, Peters JI, et al. The impact of pulmonary diseases on the fate of inhaled medicines–a review. Int J Pharm. 2014 Jan 30;461(1–2):112–128.
   PubMed Web of Science ®Google Scholar
• Haque S, Feeney O, Meeusen E, et al. Local inflammation alters the lung disposition of a drug loaded pegylated liposome after pulmonary dosing to rats. J Control Release. 2019 Aug 10;307:32–43.
   PubMed Web of Science ®Google Scholar