Carrier interactions with the biological barriers of the lung: Advanced in vitro models and challenges for pulmonary drug delivery

Advanced Drug Delivery Reviews

Volumn 75, Issue , 2014, Pages 129-140

  de Souza Carvalho, Cristiane ^a,c   Daum, Nicole ^a,c   Lehr, Claus Michael ^a,b,c  

^a SAARLAND UNIVERSITY   (Germany)

^b SAARLAND UNIVERSITY   (Germany)

^c HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

Author keywords

3D cell culture; Air blood barrier; Challenge; Mucus; Particles; Surfactant

Indexed keywords

BIOLOGICAL ORGANS; BLOOD; CELL CULTURE; ELEMENTARY PARTICLES; SURFACE ACTIVE AGENTS; TARGETED DRUG DELIVERY; TISSUE ENGINEERING;

3-D CELL CULTURE; BIOLOGICAL BARRIER; CARRIER INTERACTIONS; CARRIER TECHNOLOGY; CHALLENGE; MUCUS; PARTICLE DEPOSITIONS; PULMONARY DRUG DELIVERY;

CONTROLLED DRUG DELIVERY;

DRUG CARRIER;

BRONCHUS MUCOSA; CELL CULTURE; CELL DIFFERENTIATION; DENDRITIC CELL; DRUG DELIVERY SYSTEM; DRUG TARGETING; HUMAN; IMMUNE SYSTEM; IN VITRO STUDY; LUNG ALVEOLUS CELL; LUNG ALVEOLUS EPITHELIUM; LUNG ALVEOLUS MACROPHAGE; MICROFLUIDICS; NCI H441 CELL LINE; NONHUMAN; PARTICLE SIZE; PULMONARY DRUG DELIVERY SYSTEM; RESPIRATORY TRACT MUCOSA; REVIEW; SINGLE CELL ANALYSIS; TISSUE SCAFFOLD; AIR; ANIMAL; BIOLOGICAL MODEL; BLOOD; CULTURE TECHNIQUE; INHALATIONAL DRUG ADMINISTRATION; LUNG; METABOLISM; TISSUE ENGINEERING;

ADMINISTRATION, INHALATION; AIR; ANIMALS; BLOOD; CELL CULTURE TECHNIQUES; DRUG CARRIERS; HUMANS; LUNG; MODELS, BIOLOGICAL; TISSUE ENGINEERING;

EID: 84908253462     PISSN: 0169409X     EISSN: 18728294     Source Type: Journal    
DOI: 10.1016/j.addr.2014.05.014     Document Type: Review

References (109)

1. Ruge C.A., Kirch J., Lehr C.-M. Pulmonary drug delivery: from generating aerosols to overcoming biological barriers-therapeutic possibilities and technological challenges. Lancet Respir. Med. 2013, 1:402-413.
2. Fernandes C.A., Vanbever R. Preclinical models for pulmonary drug delivery. Expert Opin. Drug Deliv. 2009, 6:1231-1245.
3. Sporty J.L., Horalkova L., Ehrhardt C. In vitro cell culture models for the assessment of pulmonary drug disposition. Expert Opin. Drug Metab. Toxicol. 2008, 4:333-345.
4. Müller L., Riediker M., Wick P., Mohr M., Gehr P., Rothen-Rutishauser B. Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways. J. R. Soc. Interface 2010, 7:S27-S40.
5. Forbes B., Ehrhardt C. Human respiratory epithelial cell culture for drug delivery applications. Eur. J. Pharm. Biopharm. 2005, 60:193-205.
6. Rawlins E.L., Hogan B.L.M. Epithelial stem cells of the lung: privileged few or opportunities for many?. Development 2006, 133:2455-2465.
7. Rock J.R., Hogan B.L.M. Epithelial progenitor cells in lung development, maintenance, repair, and disease. Annu. Rev. Cell Dev. Biol. 2011, 27:493-512.
8. Fehrenbach H. Alveolar epithelial type II cell: defender of the alveolus revisited. Respir. Res. 2001, 2:33-46.
9. Zheng D., Limmon G.V., Yin L., Leung N.H.N., Yu H., Chow V.T.K., Chen J. A cellular pathway involved in clara cell to alveolar type ii cell differentiation after severe lung injury. PLoS One 2013, 8:e71028.
10. Smart J.D. The basics and underlying mechanisms of mucoadhesion. Adv. Drug Deliv. Rev. 2005, 57:1556-1568.
11. Antunes M.B., Cohen N.A. Mucociliary clearance-a critical upper airway host defense mechanism and methods of assessment. Curr. Opin. Allergy Clin. Immunol. 2007, 7:5-10.
12. Boucher R.C. Evidence for airway surface dehydration as the initiating event in CF airway disease. J. Intern. Med. 2007, 261:5-16.
13. Button B.M., Button B. Structure and function of the mucus clearance system of the lung. Cold Spring Harb. Perspect. Med. 2013, 3.
14. Knowles M.R., Boucher R.C. Mucus clearance as a primary innate defense mechanism for mammalian airways. J. Clin. Invest. 2002, 109:571-577.
15. Randell S.H., Boucher R.C. Effective mucus clearance is essential for respiratory health. Am. J. Respir. Cell Mol. Biol. 2006, 35:20-28.
16. Sigurdsson H.H., Kirch J., Lehr C.M. Mucus as a barrier to lipophilic drugs. Int. J. Pharm. 2013, 453:56-64.
17. Wright J.R. Immunoregulatory functions of surfactant proteins. Nat. Rev. Immunol. 2005, 5:58-68.
18. Kuroki Y., Takahashi M., Nishitani C. Pulmonary collectins in innate immunity of the lung. Cell. Microbiol. 2007, 9:1871-1879.
19. Seaton B.A., Crouch E.C., McCormack F.X., Head J.F., Hartshorn K.L., Mendelsohn R. Review: structural determinants of pattern recognition by lung collectins. Innate Immun. 2010, 16:143-150.
20. Chroneos Z.C., Midde K., Sever-Chroneos Z., Jagannath C. Pulmonary surfactant and tuberculosis. Tuberculosis 2009, 89(Supplement 1):S10-S14.
21. Glasser J.R., Mallampalli R.K. Surfactant and its role in the pathobiology of pulmonary infection. Microbes Infect. 2012, 14:17-25.
22. Willems C.H., Zimmermann L.J., Langen R.M., van den Bosch M.J., Kloosterboer N., Kramer B.W., van Iwaarden J.F. Surfactant protein A influences reepithelialization in an alveolocapillary model system. Lung 2012, 190:661-669.
23. Blusse van Oud Alblas A., van der Linden-Schrever B., van Furth R. Origin and kinetics of pulmonary macrophages during an inflammatory reaction induced by intravenous administration of heat-killed bacillus Calmette-Guerin. J. Exp. Med. 1981, 154:235-252.
24. Bowden D.H. The alveolar macrophage. Environ. Health Perspect. 1984, 55:327-341.
25. Gordon S., Taylor P.R. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 2005, 5:953-964.
26. Fathi M., Johansson A., Lundborg M., Orre L., Skold C.M., Camner P. Functional and morphological differences between human alveolar and interstitial macrophages. Exp. Mol. Pathol. 2001, 70:77-82.
27. Jakubzick C., Tacke F., Llodra J., van Rooijen N., Randolph G.J. Modulation of dendritic cell trafficking to and from the airways. J. Immunol. 2006, 176:3578-3584.
28. Geissmann F., Manz M.G., Jung S., Sieweke M.H., Merad M., Ley K. Development of monocytes, macrophages, and dendritic cells. Science 2010, 327:656-661.
29. Vermaelen K.Y., Carro-Muino I., Lambrecht B.N., Pauwels R.A. Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes. J. Exp. Med. 2001, 193:51-60.
30. Kaech S.M., Hemby S., Kersh E., Ahmed R. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 2002, 111:837-851.
31. Kosanovic D., Dahal B.K., Wygrecka M., Reiss I., Gunther A., Ghofrani H.A., Weissmann N., Grimminger F., Seeger W., Schermuly R.T., Banat G.A. Mast cell chymase: an indispensable instrument in the pathological symphony of idiopathic pulmonary fibrosis?. Histol. Histopathol. 2013, 28:691-699.
32. Takai S., Jin D., Muramatsu M., Okamoto Y., Miyazaki M. Therapeutic applications of chymase inhibitors in cardiovascular diseases and fibrosis. Eur. J. Pharmacol. 2004, 501:1-8.
33. Simon D.B., Lu Y., Choate K.A., Velazquez H., Al-Sabban E., Praga M., Casari G., Bettinelli A., Colussi G., Rodriguez-Soriano J., McCredie D., Milford D., Sanjad S., Lifton R.P. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 1999, 285:103-106.
34. Pezzulo A.A., Starner T.D., Scheetz T.E., Traver G.L., Tilley A.E., Harvey B.G., Crystal R.G., McCray P.B., Zabner J. The air-liquid interface and use of primary cell cultures are important to recapitulate the transcriptional profile of in vivo airway epithelia. Am. J. Physiol. Lung Cell. Mol. Physiol. 2011, 300:L25-L31.
35. Wu R., Wu M.M. Effects of retinoids on human bronchial epithelial cells: differential regulation of hyaluronate synthesis and keratin protein synthesis. J. Cell. Physiol. 1986, 127:73-82.
36. Wu R., Zhao Y.H., Chang M.M. Growth and differentiation of conducting airway epithelial cells in culture. Eur. Respir. J. 1997, 10:2398-2403.
37. Krunkosky T.M., Jordan J.L., Chambers E., Krause D.C. Mycoplasma pneumoniae host-pathogen studies in an air-liquid culture of differentiated human airway epithelial cells. Microb. Pathog. 2007, 42:98-103.
38. Dvorak A., Tilley A.E., Shaykhiev R., Wang R., Crystal R.G. Do airway epithelium air-liquid cultures represent the in vivo airway epithelium transcriptome. Am. J. Respir. Cell Mol. Biol. 2011, 44:465-473.
39. Grainger C.I., Greenwell L.L., Lockley D.J., Martin G.P., Forbes B. Culture of Calu-3 cells at the air interface provides a representative model of the airway epithelial barrier. Pharm. Res. 2006, 23:1482-1490.
40. Fiegel J., Ehrhardt C., Schaefer U.F., Lehr C.M., Hanes J. Large porous particle impingement on lung epithelial cell monolayers-toward improved particle characterization in the lung. Pharm. Res. 2003, 20:788-796.
41. Hein S., Bur M., Kolb T., Muellinger B., Schaefer U.F., Lehr C.M. The Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) in vitro system: design and experimental protocol. Altern. Lab. Anim. 2010, 38:285-295.
42. Lenz A.-G., Stoeger T., Cei D., Schmidmeir M., Pfister N., Burgstaller G., Lentner B., Eickelberg O., Meiners S., Schmid O. Efficient bioactive delivery of aerosolized drugs to human pulmonary epithelial cells cultured at air-liquid interface conditions. Am. J. Respir. Cell Mol. Biol. 2014, 10.1165/rcmb.2013-0479OC.
43. Wall D.A., Pierdomenico D., Wilson G. An in vitro pulmonary epithelial system for evaluating peptide transport. J. Control. Release 1993, 24:227-234.
44. Gnadt M., Trammer B., Kardziev B., Bayliss M.K., Edwards C.D., Schmidt M., Hogger P. Comparison of the bronchodilating effects of inhaled beta(2)-agonists after methacholine challenge in a human lung reperfusion model. Eur. J. Pharm. Biopharm. 2012, 81:617-626.
45. Mathias N.R., Kim K.J., Lee V.H. Targeted drug delivery to the respiratory tract: solute permeability of air-interface cultured rabbit tracheal epithelial cell monolayers. J. Drug Target. 1996, 4:79-86.
46. Lin H., Li H., Cho H.-J., Bian S., Roh H.-J., Lee M.-K., Kim J.S., Chung S.-J., Shim C.-K., Kim D.-D. Air-liquid interface (ALI) culture of human bronchial epithelial cell monolayers as an in vitro model for airway drug transport studies. J. Pharm. Sci. 2007, 96:341-350.
47. Johnson L.G., Dickman K.G., Moore K.L., Mandel L.J., Boucher R.C. Enhanced Na+ transport in an air-liquid interface culture system. Am. J. Physiol. 1993, 264:L560-L565.
48. Ehrhardt C., Fiegel J., Fuchs S., Abu-Dahab R., Schaefer U.F., Hanes J., Lehr C.M. Drug absorption by the respiratory mucosa: cell culture models and particulate drug carriers. J. Aerosol Med. 2002, 15:131-139.
49. Reddel RR D.S.R., Duncan E.L., Rogan E.M., Whitaker N.J., Zahra D.G., Ke Y., McMenamin M.G., Gerwin B.I., Harris C.C. SV40-induced immortalization and ras-transformation of human bronchial epithelial cells. Int. J. Cancer 1995, 61:7.
50. Elbert K.J., Schafer U.F., Schafers H.J., Kim K.J., Lee V.H., Lehr C.M. Monolayers of human alveolar epithelial cells in primary culture for pulmonary absorption and transport studies. Pharm. Res. 1999, 16:601-608.
51. Daum N., Kuehn A., Hein S., Schaefer U.F., Huwer H., Lehr C.M. Isolation, cultivation, and application of human alveolar epithelial cells. Methods Mol. Biol. 2012, 806:31-42.
52. Kemp S.J., Thorley A.J., Gorelik J., Seckl M.J., O'Hare M.J., Arcaro A., Korchev Y., Goldstraw P., Tetley T.D. Immortalization of human alveolar epithelial cells to investigate nanoparticle uptake. Am. J. Respir. Cell Mol. Biol. 2008, 39:591-597.
53. van den Bogaard E.H., Dailey L.A., Thorley A.J., Tetley T.D., Forbes B. Inflammatory response and barrier properties of a new alveolar type 1-like cell line (TT1). Pharm. Res. 2009, 26:1172-1180.
54. Sporty J.L., Horálková L., Ehrhardt C. In vitro cell culture models for the assessment of pulmonary drug disposition. Expert Opin. Drug Metab. Toxicol. 2008, 4:333-345.
55. Salomon J.J., Muchitsch V.E., Gausterer J.C., Schwagerus E., Huwer H., Daum N., Lehr C.-M., Ehrhardt C. The cell line NCl-H441 is a useful in vitro model for transport studies of human distal lung epithelial barrier. Mol. Pharm. 2014, 11:995-1006.
56. Gumbleton M., Al-Jayyoussi G., Crandon-Lewis A., Francombe D., Kreitmeyr K., Morris C.J., Smith M.W. Spatial expression and functionality of drug transporters in the intact lung: objectives for further research. Adv. Drug Deliv. Rev. 2011, 63:110-118.
57. Endter S., Francombe D., Ehrhardt C., Gumbleton M. RT-PCR analysis of ABC, SLC and SLCO drug transporters in human lung epithelial cell models. J. Pharm. Pharmacol. 2009, 61:583-591.
58. Guilliams M., Lambrecht B.N., Hammad H. Division of labor between lung dendritic cells and macrophages in the defense against pulmonary infections. Mucosal Immunol. 2013, 6:464-473.
59. Raschke W.C., Baird S., Ralph P., Nakoinz I. Functional macrophage cell lines transformed by Abelson leukemia virus. Cell 1978, 15:261-267.
60. Ruge C.A., Kirch J., Canadas O., Schneider M., Perez-Gil J., Schaefer U.F., Casals C., Lehr C.M. Uptake of nanoparticles by alveolar macrophages is triggered by surfactant protein A. Nanomedicine 2011, 7:690-693.
61. Tsuchiya S., Kobayashi Y., Goto Y., Okumura H., Nakae S., Konno T., Tada K. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 1982, 42:1530-1536.
62. Terpstra G.K., De Weger R.A., Wassink G.A., Kreuknit J., Huidekoper H.J. Changes in alveolar macrophage enzyme content and activity in smokers and patients with chronic obstructive lung disease. Int. J. Clin. Pharmacol. Res. 1987, 7:273-277.
63. Taylor A.E., Finney-Hayward T.K., Quint J.K., Thomas C.M.R., Tudhope S.J., Wedzicha J.A., Barnes P.J., Donnelly L.E. Defective macrophage phagocytosis of bacteria in COPD. Eur. Respir. J. 2010, 35:1039-1047.
64. Balhara J., Gounni A.S. The alveolar macrophages in asthma: a double-edged sword. Mucosal Immunol. 2012, 5:605-609.
65. Lambrecht B.N., Hammad H. Taking our breath away: dendritic cells in the pathogenesis of asthma. Nat. Rev. Immunol. 2003, 3:994-1003.
66. Hardy C.L., LeMasurier J.S., Mohamud R., Yao J., Xiang S.D., Rolland J.M., O'Hehir R.E., Plebanski M. Differential uptake of nanoparticles and microparticles by pulmonary APC subsets induces discrete immunological imprints. J. Immunol. 2013, 191:5278-5290.
67. Rothen-Rutishauser B.M., Kiama S.G., Gehr P. A three-dimensional cellular model of the human respiratory tract to study the interaction with particles. Am. J. Respir. Cell Mol. Biol. 2005, 32:281-289.
68. Rescigno M., Borrow P. The host-pathogen interaction: new themes from dendritic cell biology. Cell 2001, 106:267-270.
69. Rescigno U.M., Valzasina B., Francolini M., Rotta G., Bonasio R., Granucci F., Kraehenbuhl J.P., Ricciardi-Castagnoli P. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat. Immunol. 2001, 2:361-367.
70. Blank F., Rothen-Rutishauser B., Gehr P. Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am. J. Respir. Cell Mol. Biol. 2007, 36:669-677.
71. Blank F., Wehrli M., Lehmann A., Baum O., Gehr P., von Garnier C., Rothen-Rutishauser B.M. Macrophages and dendritic cells express tight junction proteins and exchange particles in an in vitro model of the human airway wall. Immunobiology 2011, 216:86-95.
72. Blank F., Rothen-Rutishauser B.M., Schurch S., Gehr P. An optimized in vitro model of the respiratory tract wall to study particle cell interactions. J. Aerosol Med. 2006, 19:13.
73. Lehmann A.D., Daum N., Bur M., Lehr C.-M., Gehr P., Rothen-Rutishauser B.M. An in vitro triple cell co-culture model with primary cells mimicking the human alveolar epithelial barrier. Eur. J. Pharm. Biopharm. 2011, 77:398-406.
74. Alfaro-Moreno E., Nawrot T.S., Vanaudenaerde B.M., Hoylaerts M.F., Vanoirbeek J.A., Nemery B., Hoet P.H.M. Co-cultures of multiple cell types mimic pulmonary cell communication in response to urban PM10. Eur. Respir. J. 2008, 32:1184-1194.
75. Klein S.G., Hennen J., Serchi T., Blömeke B., Gutleb A.C. Potential of coculture in vitro models to study inflammatory and sensitizing effects of particles on the lung. Toxicol. in Vitro 2011, 25:1516-1534.
76. Klein S.G., Serchi T., Hoffmann L., Blmeke B., Gutleb A.C. An improved 3D tetraculture system mimicking the cellular organisation at the alveolar barrier to study the potential toxic effects of particles on the lung. Part Fibre. Toxicol. 2013, 10:1-18.
77. Rothen-Rutishauser B., Mueller L., Blank F., Brandenberger C., Muehlfeld C., Gehr P. A newly developed in vitro model of the human epithelial airway barrier to study the toxic potential of nanoparticles. Altex 2008, 25:191-196.
78. Schleh C., Rothen-Rutishauser B.M., Blank F., Lauenstein H.D., Nassimi M., Krug N., Braun A., Erpenbeck V.J., Gehr P., Hohlfeld J.M. Surfactant protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model. Respir. Res. 2012, 13:8.
79. Erpenbeck V.J., Malherbe D.C., Sommer S., Schmiedl A., Steinhilber W., Ghio A.J., Krug N., Wright J.R., Hohlfeld J.M. Surfactant protein D increases phagocytosis and aggregation of pollen-allergen starch granules. Am. J. Physiol. Lung Cell. Mol. Physiol. 2005, 288:L692-L698.
80. Franzdottir S., Axelsson I., Arason A., Baldursson O., Gudjonsson T., Magnusson M. Airway branching morphogenesis in three dimensional culture. Respir. Res. 2010, 11:162.
81. Gill B.J., Gibbons D.L., Roudsari L.C., Saik J.E., Rizvi Z.H., Roybal J.D., Kurie J.M., West J.L. A synthetic matrix with independently tunable biochemistry and mechanical properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma model. Cancer Res. 2012, 72:6013-6023.
82. Brahatheeswaran Dhandayuthapani Y.Y., Maekawa Toru, Sakthi Kumar D. Polymeric scaffolds in tissue engineering application: a review. Int. J. Polym. Sci. 2011, 349-364.
83. Lutolf M.P., Hubbell J.A. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat. Biotechnol. 2005, 23:47-55.
84. Xi T.F., Fan C.X., Feng X.M., Wan Z.Y., Wang C.R., Chou L.L. Cytotoxicity and altered c-myc gene expression by medical polyacrylamide hydrogel. J. Biomed. Mater. Res. A 2006, 78A:283-290.
85. Nalayanda D.D., Puleo C.M., Fulton W.B., Wang T.-H., Abdullah F. Characterization of pulmonary cell growth parameters in a continuous perfusion microfluidic environment. Exp. Lung Res. 2007, 33:321-335.
86. Nalayanda D., Puleo C., Fulton W., Sharpe L., Wang T.-H., Abdullah F. An open-access microfluidic model for lung-specific functional studies at an air-liquid interface. Biomed. Microdevices 2009, 11:1081-1089.
87. Nalayanda D.D., Wang Q., Fulton W.B., Wang T.-H., Abdullah F. Engineering an artificial alveolar-capillary membrane: a novel continuously perfused model within microchannels. J. Pediatr. Surg. 2010, 45:45-51.
88. Huh D., Matthews B.D., Mammoto A., Montoya-Zavala M., Hsin H.Y., Ingber D.E. Reconstituting organ-level lung functions on a chip. Science 2010, 328:1662-1668.
89. Huh D., Leslie D.C., Matthews B.D., Fraser J.P., Jurek S., Hamilton G.A., Thorneloe K.S., McAlexander M.A., Ingber D.E. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci. Transl. Med. 2012, 4:159ra147.
90. Huh D., Hamilton G.A., Ingber D.E. From 3D cell culture to organs-on-chips. Trends Cell Biol. 2011, 21:745-754.
91. Schürch D., Vanhecke D., Clift M.J.D., Raemy D., de Aberasturi D.J., Parak W.J., Gehr P., Petri-Fink A., Rothen-Rutishauser B. Modeling nanoparticle-alveolar epithelial cell interactions under breathing conditions using captive bubble surfactometry. Langmuir 2014, 30:4924-4932.
92. Schurch S., Bachofen H., Goerke J., Possmayer F. A captive bubble method reproduces the in situ behavior of lung surfactant monolayers. J. Appl. Physiol. 1989, 67:2389-2396.
93. Edwards D.A., Ben-Jebria A., Langer R. Recent advances in pulmonary drug delivery using large, porous inhaled particles. J. Appl. Physiol. 1998, 85:379-385.
94. Geiser M. Update on macrophage clearance of inhaled micro- and nanoparticles. J. Aerosol Med. Pulm. Drug Deliv. 2010, 23:207-217.
95. Champion J.A., Mitragotri S. Shape induced inhibition of phagocytosis of polymer particles. Pharm. Res. 2009, 26:244-249.
96. Sturm R., Hofmann W. A theoretical approach to the deposition and clearance of fibers with variable size in the human respiratory tract. J. Hazard. Mater. 2009, 170:210-218.
97. Tsapis N., Bennett D., Jackson B., Weitz D.A., Edwards D.A. Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:12001-12005.
98. Kohler D., Schneider M., Kruger M., Lehr C.M., Mohwald H., Wang D. Template-assisted polyelectrolyte encapsulation of nanoparticles into dispersible, hierarchically nanostructured microfibers. Adv. Mater. 2011, 23:1376-1379.
99. Herd H., Daum N., Jones A.T., Huwer H., Ghandehari H., Lehr C.M. Nanoparticle geometry and surface orientation influence mode of cellular uptake. ACS Nano 2013, 7:1961-1973.
100. Sakagami M., Byron P.R. Respirable microspheres for inhalation: the potential of manipulating pulmonary disposition for improved therapeutic efficacy. Clin. Pharmacokinet. 2005, 44:263-277.
101. Berglind Eva Benediktsdóttir O.l.B., Másson Már Challenges in evaluation of chitosan and trimethylated chitosan (TMC) as mucosal permeation enhancers: from synthesis to in vitro application. J. Control. Release 2014, 173:18-31.
102. Takeuchi H., Yamamoto H., Kawashima Y. Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv. Drug Deliv. Rev. 2001, 47:39-54.
103. Frohlich E., Roblegg E. Mucus as barrier for drug delivery by nanoparticles. J. Nanosci. Nanotechnol. 2014, 14:126-136.
104. Lai S.K., Wang Y.-Y., Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv. Drug Deliv. Rev. 2009, 61:158-171.
105. Lai S.K., O'Hanlon D.E., Harrold S., Man S.T., Wang Y.-Y., Cone R., Hanes J. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc. Natl. Acad. Sci. 2007, 104:1482-1487.
106. Ensign LM T.B., Wang Y.Y., Tse T.A., Hoen T., Cone R., Hanes J. Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci. Transl. Med. 2012, 4:22.
107. Dames P., Gleich B., Flemmer A., Hajek K., Seidl N., Wiekhorst F., Eberbeck D., Bittmann I., Bergemann C., Weyh T., Trahms L., Rosenecker J., Rudolph C. Targeted delivery of magnetic aerosol droplets to the lung. Nat. Nanotechnol. 2007, 2:495-499.
108. Anabousi S., Bakowsky U., Schneider M., Huwer H., Lehr C.M., Ehrhardt C. In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer. Eur. J. Pharm. Sci. 2006, 29:367-374.
109. Gaspar M.M., Radomska A., Gobbo O.L., Bakowsky U., Radomski M.W., Ehrhardt C. Targeted delivery of transferrin-conjugated liposomes to an orthotopic model of lung cancer in nude rats. J. Aerosol Med. Pulm. Drug Deliv. 2012, 25:310-318.