Destructive methods of mucolysis degrade the mucin gel networks by reducing the size of the mucins. Doing so aids in reducing the elasticity of the mucin, allowing them to be cleared efficiently through airflow clearance (cough)192 but does not typically assist the burden of ciliary clearance. Dornase alfa is a highly-utilized example. It is the recombinant human enzyme DNase I and has demonstrated the ability to reduce sputum viscosity.193 It does so by decreasing the size of DNA molecules within sputum, which are the leading cause of the high viscosity of
sputum.194 Dornase alfa does not over-reduce these molecules to a point of liquefying the mucus gel so that it retains its necessary functionalities, and was the first FDA approved mucolytic prescribed in the United States.195,196
N-acetylcysteine (NAC) is another common destructive mucolytic agent. It is a thiol reducing agent that reduces the viscosity of sputum via mucin-chain scission, and though not used heavily in North America, has shown efficacy in aiding the clearance of sputum in COPD and CF patients.197 NAC reduces disulfide bonds within the mucus gel network to free thiols. As more novel disulfide reducing agents have been synthesized by today’s drug makers, NAC was found not to be a very efficient therapeutic mucolytic though early in vitro data was
promising.198-200 The reason for this is unknown and currently being studied by researchers worldwide.
1.4.4 Characterization of Mucins 1.4.4.a RT-PCR
RT-PCR is used to detect gene expression qualitatively by utilizing RNA of interest to create complementary DNA transcripts.201 These transcripts are then amplified using PCR, and can be used to determine the expressed genes within a biological sample.202,203 This has been shown to be highly useful in determining MUC genes in samples166 as well as quantifying the magnitude of overexpression of MUC genes in diseased sputum samples204,205, and identifying viruses in sputum.206,207
1.4.4.b Rheology
To obtain information about the viscous and elastic modulus of mucin gels, researchers turned to trying rheology on these systems. Rheology is the study of flow, and applies a stress to samples and measures the deformation strain of the material in response to this force.208
Biological scientist can use this methodology to understand the differences between different mucins209, the mucin response under different pH conditions210, 211, and changes in the mucin network after mucolysis methods have been applied.212
1.4.4.c Mass Spectrometry
Mass spectrometry methods have been a great tool to both quantify mucins213 and characterize them down to the peptides which make them up.214 Its use has changed the way scientist can analyze these intricate gels. Utilizing mass spectrometry as a detector after chromatography methods has been quite beneficial for size information and understanding the major MUC genes at different locations of the respiratory tract.215
1.4.4.d. Western Blot
To grasp understanding of the molecular weight of mucins and how their size is affected under various conditions, western blot is performed. Western blotting is the staple procedure in biomedical research for determining the rough molecular weight of a biological molecule. It involves the gel electrophoresis of native proteins which are stained with antibodies, and determining their size based on the resolution of the stained band they create in references to a marker of known size.216, 217 This method is what has given the molecular weight estimates of the identified MUC genes to-date. Western blot testing has shown that MUC5B and MUC5AC are of molecular weights larger than 25 MDa, but because of the nature of the test, cannot provide accurate quantitative data.218, 219
1.4.5 Research Objectives
To address the inability to obtain accurate data on the molecular weight of mucins, new characterization protocols must be installed. In this report, we propose the use of gel permeation chromatography (GPC) to afford useable data with high impact for drug development and to aid
the overall scientific understanding of mucin gel networks in the battle of pulmonary diseases. This tool will allow researchers to investigate the role of mucus in lowering patient wellbeing and fight mucin overexpression.
REFERENCES
1. Stevens, M. P.; Polymer Chemistry an Introduction 1999, 3, 175. 2. Schoff, C. K.; J. Coat. Tech. 1999, 71, 888, 57-72.
3. Kornum, L. O.; Raaschou Nielsen, H. K.; Prog. Org. Coat. 1980, 8, 275-324. 4. Bierwagen, G. F.; Prog. Org. Coat. 1975, 3, 101-113.
5. Fink-Jensen, Farbe Lack 1962, 68, 155-162.
6. Patton, T. C.; J. Paint Technol. 1966, 38, 502, 656-666. 7. Orchard, S. E.; Appl. Sci. Res. A 1962, 11, 451.
8. Smith, N. P. D.; Orchard, S. E.; Rhind-Tutt, A. J.; J. Oil Colour Chem. Assoc. 1961, 44, 618. 9. Overdiep, W. S.; Physiochemical Hydrodynamics, in: D.B. Spalding (Ed.) 1978, 683.
10.Overdiep, W.S.; Prog. Org. Coat. 1986, 14, 159.
11.Hawe, M.; Handbook of Industrial water soluble polymers 2007, 32-72.
12.Bosma, M.; Brinkhuis, R.; Rensen, E.; Watson, R., Prog. Org. Coat. 2011, 26-33. 13.Cramer, S.; Speiss, W.; Macromol. Chem. Phys. 2002, 203, 192-198.
14.Gerlock, J.; Bauer, D.; Polymer Degradation and Stability 1988, 20, 123-134. 15.Sim, S.; Forbes, M. D. E.; J. Phys. Chem. B 2014, 118, 9997-10006.
16. Goldstein, N.; BioCycle 2012 , 53, 1, 4.
17.Ratner, B.; Hoffman, A.; Schoen, F.; Lemons, J.; Biomaterials Science 2012, 3, 179-181. 18. Martina, M.; Hutmacher, D. W.; Polym. Int. 2007, 56, 145.
19.Xie, J.; Lee, S.; Chen, X.; Adv. Drug Del. Rev. 2010, 62, 11, 1064-1079. 20.15. Vert, M.; Biomacromolecules 2005, 6, 538,16.
21.Morachis, J. M.; Mahmoud, E. A.; Almutairi, A.; Pharmacol. Rev. 2012, 64, 505, 17. 22.Wei, H.; Zhuo, R.-X.; Zhang, X.-Z.; Prog. Polym. Sci. 2012, 38, 503.
23.Xuan, S.; Lee, C.U.; Chen, C.; Doyle, A.B.; Zhang, Y.; Guo, L.; John, V.T.; Hayes, D.; Zhang, D.; Chem Mater 2016, 28, 3, 727-737.
24.Aseyev, V.; Tenhu, H.; Winnik, F. M.; Self Organized Nanostructures of Amphiphilic Block Copolymers II 2011, 29–89.
25.Bae, Y. C.; Lambert, S. M.; Soane, D. S.; Prausnitz, D. S.; Macromolecules 1991, 24, 4403– 4407.
26.Halperin, A.; Kröger, M.; Winnik, F. M.; Angew. Chem., Int. Ed. 2015, 54, 15342–15367. 27.Seuring, J.; Agarwal, S.; Macromol. Rapid Commun. 2012, 33, 1898–1920.
28.Zhang, Q.; Hoogenboom, R.; Prog. Polym. Sci. 2015, 48, 122–142.
29.Plamper, F. A.; Schmalz, A.; Müller, A. H. E.; J. Am. Chem. Soc. 2007, 129, 14538–14539. 30.Plamper, F. A.; Steinschulte, A. A.; Hofmann, C. H.; Drude, N.; Mergel, O.; Herbert, C.;
Erberich, M.; Schulte, B.; Winter, R.; Richtering, W.; Macromolecules 2012, 8021–8026. 31.Niskanen, J.; Wu, C.; Ostrowski, M.; Fuller, G. G.; Hietala, S.; Tenhu, H.; Macromolecules
2013, 46, 2331–2340.
32.Maeda, Y.; Ide, M.; Kitano, H.; J. Mol. Liq. 1999, 80, 149– 163. 33.Kitano, H.; Polym. J. 2016, 48, 15–24.
34.Seuring, J.; Agarwal, S.; Macromol. Chem. Phys. 2010, 211, 2109–2117. 35.Xu, H.; Meng, F.; Zhong, Z.; J. Mater. Chem. 2009,19, 4183-4190.
36.Bang, E.-K.; Lista, M.; Sforazzini, G.; Sakai, N.; Matile, S.; Chem. Sci. 2012, 3, 1752. 37.Ko, N. R.; Yao, K.; Tang, C.; Oh, J. K.; J. Polym. Sci. A Polym. Chem. 2013, 51, 3071-3080. 38.Bauhuber, S.; Hozsa, C.; Breunig, M.; Göpferich, A.; Advanced Materials 2009, 21, 3286. 39.Emilitri, E.; Ranucci, E.; Ferruti, P.; J. Polym. Sci. A Polym. Chem. 2005, 43, 1404. 40.Meng, F.; Hennink, W. E.; Zhong, Z.; Biomaterials 2009, 30, 2180.
41.Pan, Y. J.; Chen, Y. Y.; Wang, D. R.; Wei, C.; Guo, J.; Lu, D. R.; Chu, C. C.; Wang, C. C.; Biomaterials 2012, 33, 6570.
43.Hu, J. H.; Yu, H.; Gan, L. H.; Hu, X.; Soft Matter 2011, 7, 11345–11350. 44.Lin, S. L.; Wang, Y. Y.; Cai, C. H.; Xing, Y. H.; Lin, J. P.; Chem, T.; He, X. H.;
Nanotechnology 2013, 24, 085602.
45.Jin, Q. A.; Liu, G. Y.; Liu, X. S.; Ji, J. A.; Soft Matter 2010, 6, 5589–5595.
46.Shen, G. Y.; Xue, G. S.; Cai, J.; Zou, G.; Li, Y. M.; Zhang, Q. J.; Soft Matter 2013, 9, 2512– 2517.
47.Hu, D.; Li, Y. F.; Niu, Y. L.; Li, L.; He, J. W.; Liu, X. Y.; Xia, X. N.; Lu, Y. B.; Xiong, Y. Q.; Xu, W. J.; RSC Adv. 2014, 4, 47929–47936.
48.Wei, R. B.; Ma, J. Y.; Zhang, H. X.; He, Y. N.; J. Appl. Polym. Sci. 2016, 133, 43695. 49.Wei, R. B.; Wang, X. G.; He, Y. N.; Chin. Chem. Lett. 2015, 26, 857–861.
50.Huang, G. X.; Zhu, J.; Zhang, Z. B.; Zhang, W.; Zhou, N. C.; Zhu, X. L.; J. Macromol. Sci., Part A: Pure Appl. Chem. 2013, 50, 193–199.
51.Hu, J.; Wang, X.; Zheng, S. H.; Polym. Adv. Technol. 2012, 23, 1590–1595.
52.Blasco, E.; Schmidt, B. V. K. J.; Barner-Kowollik, C.; Pinol, M.; Oriol, L.; Polym. Chem. 2013, 4, 4506–4514.
53.Guo, W. J.; Wang, T. S.; Tang, X. D.; Zhang, Q.; Yu, F. Q.; Pei, M. S.; J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2131–2138.
54.Chen, C. J.; Liu, G. Y.; Liu, X. S.; Li, D. D.; Ji, J.; New J. Chem. 2012, 36, 694–701.
55.Dong, R. J.; Liu, Y.; Zhou, Y. F.; Yan, D. Y.; Zhu, X. Y.; Polym. Chem. 2011, 2, 2771–2774. 56.Dong, S. Y.; Gao, L. Y.; Li, J. Y.; Xu, D. H.; Zhou, Q. Z.; Polym. Chem. 2013, 4, 3968–
3973.
57.Liu, L. C.; Rui, L. L.; Gao, Y.; Zhang, W. A.; Polym. Chem. 2014, 5, 5453–5460. 58.Yang, J.; Li, Z. T.; Zhou, Y. J.; Yu, G. C.; Polym. Chem. 2014, 5, 6645–6650. 59.Zhou, X. R.; Du, Y.; Wang, X. G.; ACS Macro Lett. 2016, 5, 234–237.
60.Marturano, V.; Cerruti, P.; Carfagna, C.; Giamberini, M.; Tylkowski, B.; Ambrogi, V.; Polymer 2015, 70, 222–230.
62.Yang, Y. Z.; Tang, Q.; Gong, C. B.; Ma, X. B.; Peng, J. D.; Lam, M. H. W.; New J. Chem. 2014, 38, 1780–1788.
63.Gong, C. B.; Yang, Y. Z.; Gao, C.; Tang, Q.; Chow, C. F.; Peng, J. D.; Lam, M. H. W.; J. Sol-Gel Sci. Technol. 2013, 67, 442–450.
64.Romasanta, L. J.; Lopez-Manchado, L. J.; Verdejo, R.; Prog. Polym. Sci. 2015, 51, 188–211. 65.Liu, H. L.; Zhang, L. Q.; Yang, D.; Ning, N. Y.; Yu, Y. C.; Yao, L.; Yan, B. Y.; Tian, M.; J.
Phys. D: Appl. Phys. 2012, 45, 485303.
66.Bhandari, B.; Lee, G. Y.; Ahn, S. H.; Int. J. Precis. Eng. Manuf. 2012, 13, 141–163. 67.Song, J.; Jeon, J. H.; Oh, I. K.; Park, K. C.; Macromol. Rapid Commun. 2011, 32, 1583–
1587.
68.He, Q. S.; Yu, M.; Song, L. L.; Ding, H. T.; Zhang, X. Q.; Dai, Z. D.; J. Bionic. Eng. 2011, 8, 77–85.
69.Gugliuzza, A.; Drioli, E.; J. Membr. Sci. 2013, 446, 350– 375.
70.Bhattacharya, S.; Bepari, B.; Bhaumik, S.; Mech. Based Des. Struct. Mach. 2014, 42, 312– 325.
71.Lu, J.; Kim, S. G.; Lee, S.; Oh, I. K.; Macromol. Chem. Phys. 2011, 212, 635–642. 72.Engel, L.; Kruk, S.; Shklovsky, J.; Shacham-Diamand, Y.; Krylov, S.; J. Micromech.
Microeng. 2014, 24, 125027.
73.Kim, S. S.; Kee, C. D.; Int. J. Precis. Eng. Manuf. 2014, 15, 315–321.
74.Jeon, J. H.; Oh, I. K.; Kee, C. D.; Kim, S. J.; Sens. Actuators, B 2010, 146, 307–313. 75.Kunchornsup, W.; Sirivat, A.; Sens. Actuators, A 2014, 220, 249–261.
76.Wang, X. L.; Oh, I. K.; Cheng, T. H.; Polym. Int. 2010, 59, 305–312. 77.Wang, X. L.; Oh, I. K.; Xu, L.; Sens. Actuators, B 2010, 145, 635–642.
78.Migliorini, L.; Santaniello, T.; Yan, Y. S.; Lenardi, C.; Milani, P.; Sens. Actuators, B 2016, 228, 758–766.
79.Cheedarala, R. K.; Jeon, J. H.; Kee, C. D.; Oh, I. K.; Adv. Funct. Mater. 2014, 24, 6005– 6015.
80.Morales, D.; Palleau, E.; Dickey, M. D.; Velev, O. D.; Soft Matter 2014, 10, 1337–1348. 81.Indermun, S.; Choonara, Y. E.; Kumar, P.; du Toit, L. C.; Modi, G.; Luttge, R.; Pillay, V.;
Int. J. Pharm. 2014, 462, 52–65.
82.Kwon, G. H.; Choi, Y. Y.; Park, J. Y.; Woo, D. H.; Lee, K. B.; Kim, J. H.; Lee, S. H.; Lab Chip 2010, 10, 1604–1610.
83.Jackson, N.; Cordero, N.; Stam, F.; J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1523– 1528.
84.Jackson, N.; Stam, F.; J. Appl. Polym. Sci. 2015, 132, 41687.
85.Bassil, M.; Ibrahim, M.; El Tahchi, M.; Soft Matter 2011, 7, 4833–4838.
86.Glazer, P. J.; van Erp, M.; Embrechts, A.; Lemay, S. G.; Mendes, E.; Soft Matter 2012, 8, 4421–4426.
87.Jo, C.; Naguib, H. E.; Kwon, R. H.; Smart Mater. Struct. 2011, 20, 045006.
88.Yang, C.; Wang, W.; Yao, C.; Xie, R.; Ju, X. J.; Liu, Z.; Chu, L. Y.; Sci. Rep. 2015, 5, 13622.
89.Borisova, O. V.; Billon, L.; Richter, R. P.; Reimhult, E.; Borisov, O. V.; Langmuir 2015, 31, 7684–7694.
90.Cao, Q. Q.; Zuo, C. C.; Li, L. J.; Yan, G.; Biomicrofluidics 2011, 5, 044119.
91.Wood, K. C.; Zacharia, N. S.; Schmidt, D. J.; Wrightman, S. N.; Andaya, B. J.; Hammond, P. T.; Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 2280–2285.
92.Al-Badri, Z. M.; Maddikeri, R. R.; Zha, Y. P.; Thaker, H. D.; Dobriyal, P.; Shunmugam, R.; Russell, T. P.; Tew, G. N.; Nat. Commun. 2011, 2, 482.
93.Zha, Y. P.; Maddikeri, R. R.; Gido, S. P.; Tew, G. N.; J. Inorg. Organomet. Polym. Mater. 2013, 23, 89–94.
94.Zha, Y. P.; Thaker, H. D.; Maddikeri, R. R.; Gido, S. P.; Tuominen, M. T.; Tew, G. N.; J. Am. Chem. Soc. 2012, 134, 14534–14541.
95.Mukherjee, S.; Dinda, H.; Shashank, L.; Chakraborty, I.; Bhattacharyya, R.; Das Sarma, J.; Shunmugam, R.; Macromolecules 2015, 48, 6791–6800.
96.Mukherjee, S.; Patra, D.; Dinda, H.; Chalkraborty, I.; Shashank, L.; Bhattacharyya, R.; Das Sarma, J.; Shunmugam, R.; Macromolecules 2016, 49, 2411–2418.
97.Jiang, B. Y.; Hom, W. L.; Chen, X. Y.; Yu, P. Q.; Payelka, L. C.; Kisslinger, K.; Parise, J. B.; Bhatia, S. R.; Grubbs, R. B.; J. Am. Chem. Soc. 2016, 138, 4616–4625.
98.Miao, W. G.; Qin, L.; Yang, D.; Jin, X.; Liu, M. H.; Chem. – Eur. J. 2015, 21, 1064–1072. 99.Yu, X. D.; Liu, Q. A.; Wu, J. C.; Zhang, M. M.; Cao, X. H.; Zhang, S.; Wang, Q.; Chen, L.
M.; Yi, T.; Chem. – Eur. J. 2010, 16, 9099–9106.
100. Fan, J. W.; Zou, J.; He, X.; Zhang, F. W.; Zhang, S. Y.; Raymond, J. E.; Wooley, K. L.; Chem. Sci. 2014, 5, 141– 150.
101.Min, Y. Q.; Huang, S. Y.; Wang, Y. X.; Zhang, Z. J.; Du, B. Y.; Zhang, X. H.; Fan, Z. Q.; Macromolecules 2015, 48, 316– 322.
102.Schaefer, M.; Icli, B.; Weder, C.; Lattuada, M.; Kilbinger, A. F. M.; Simon, Y. C.; Macromolecules 2016, 49, 1630–1636.
103.Sommer, M.; Komber, H.; Macromol. Rapid Commun. 2013, 34, 57–62. 104.Chen, W. Q.; Du, J. Z.; Sci. Rep. 2013, 3, 2162.
105.Gao, Z. G.; Fain, H. D.; Rapoport, N.; J. Controlled Release 2005, 102, 203–222. 106.Husseini, G. A.; Myrup, G. D.; Pitt, W. G.; Christensen, D. A.; Rapoport, N. Y.; J.
Controlled Release 2000, 69, 43– 52.
107.Marin, A.; Sun, H.; Husseini, G. A.; Pitt, W. G.; Christensen, D. A.; Rapoport, N. Y.; J. Controlled Release 2002, 84, 39–47.
108.Rapoport, N. Y.; Int. J. Pharm. 2004, 277, 155–162.
109.Rapoport, N. Y.; Christensen, D. A.; Fain, H. D.; Barrows, L.; Gao, Z.; Ultrasonics 2004, 42, 943–950.
110.Rapoport, N. Y.; Kennedy, A. M.; Shea, J. E.; Scaife, C. L.; Nam, K. H.; J. Controlled Release 2009, 138, 268– 276.
111.Zhang, H. J.; Xia, H. S.; Wang, J.; Li, Y. W.; J. Controlled Release 2009, 139, 31–39. 112.Narayan, R. In Science and Engineering of Composting: Design, Environmental,
Microbiological and Utilization Aspects 1993, 339.
114.Thompson, R. C.; Olsen, Y.; Mitchell, R. P.; Davis, A.; Rowland, S. J.; John, A. W. G.; McGonigle, D.; Russell, A. E.; Science 2004, 304, 838.
115.Mato, Y; Isobe, T; Takada, H; Kahnehiro, H; Ohtake, C; Kaminuma, T.; Environ. Sci. Technol. 2001, 35, 318–324.
116.Thompson, R. C.; Olsen, Y.; Mitchell, R. P.; Davis, A.; Rowland, S. J.; John, A. W. G.; McGonigle, D.; Russell, A. E.; Philos. Trans. R. Soc. B 2009, 364.
117.Stevens, M. P.; Polymer Chemistry: an Introduction 1999, 3, 193-194. 118.Shabat, D. J.; J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 1569-1578.
119.Peterson, G. I.; Larsen, M. B.; Boydston, A. J.; Macromolecules 2012, 45, 7317-7328. 120.de Groot, F. M. H.; Loos, W. J.; Kockkock, R.; van Berkom, L. W. A.; Busscher, G. F.;
Seelen, A. E.; Albreccht, C.; de Bruijn, P.; Scheeren, H. W.; J. Org. Chem. 2001, 66, 8815−8830.
121.de Groot, F. M. H.; Albrecht, C.; Koekkoek, R.; Beusker, P. H.; Scheeren, H. W.; Angew. Chem., Int. Ed. 2003, 42, 4490−4494.
122.Li, S.; Szalai, M. L.; Kevwitch, R. M.; McGrath, D. V.; J. Am. Chem. Soc. 2003, 125, 10516−10517.
123.Amir, R. J.; Pessah, N.; Shamis, M.; Shabat, D.; Angew. Chem., Int. Ed. 2003, 42, 4494−4499.
124.Esser-Kahn, A. P.; Odom, S. A.; Sottos, N. R.; White, S. R.; Moore, J. S.; Macromolecules 2011, 44, 5539−5553.
125.Avital-Shmilovici, M.; Shabat, D.; Soft Matter 2010, 6, 1073−1080.
126.Wong, A. D.; DeWit, M. A.; Gillies, E. R.; Adv. Drug Delivery Rev. 2012, 11, 1031-1045. 127.Shamis, M.; Lode, H. N.; Shabat, D.; J. Am. Chem. Soc. 2004, 126, 1726−1731.
128.Haba, K.; Popkov, M.; Shamis, M.; Lerner, R. A.; Barbas, C. F., III; Shabat, D.; Angew. Chem., Int. Ed. 2005, 44, 716−720.
129.Sagi, A.; Segal, E.; Satchi-Fainaro, R.; Shabat, D.; Bioorg. Med. Chem. 2007, 15, 3720−3727.
130.Amir, R. J.; Popkov, M.; Lerner, R. A.; Barbas, C. F., III; Shabat, D.; Angew. Chem., Int. Ed. 2005, 44, 4378−4381.
131.Danieli, E.; Shabat, D.; Bioorg. Med. Chem. 2007, 15, 7318−7324. 132.Shamis, M.; Shabat, D.; Chem. Eur. J. 2007, 13, 4523−4528.
133.Adler-Abramovich, L.; Perry, R.; Sagi, A.; Gazit, E.; Shabat, D.; Chem. BioChem. 2007, 8, 859−862.
134.Amir, R. J.; Danieli, E.; Shabat, D.; Chem. Eur. J. 2007, 13, 812−821.
135.Sagi, A.; Weinstain, R.; Karton, N.; Shabat, D.; J. Am. Chem. Soc. 2008, 130, 5434−5435. 136.Weinstain, R.; Sagi, A.; Karton, N.; Shabat, D.; Chem. Eur. J. 2008, 14, 6857−6861. 137.Weinstain, R.; Baran, P. S.; Shabat, D.; Bioconjugate Chem. 2009, 20, 1783−1791. 138.Shamis, M.; Lode, H. N.; Shabat, D.; J. Am. Chem. Soc. 2004, 126, 1726−1731.
139.Grinda, M.; Clarhaut, J.; Renoux, B.; Tranoy-Opalinski, I.; Papot, S.; Med. Chem. Commun. 2012, 3, 68−70.
140.DeWit, M. A.; Gillies, E. R.; J. Am. Chem. Soc. 2009, 131, 18327−18334. 141.Perry, R.; Amir, R. J.; Shabat, D.; New J. Chem. 2007, 31, 1307−1312.
142.Esser-Kahn, A. P.; Sottos, N. R.; White, S. R.; Moore, J. S.; J. Am. Chem. Soc. 2010, 132, 10266−10268.
143.Moore, K.; Photomedicine and Laser Surgery. 2013, 12,563–564.
144.Kevwitch, R. M.; Shanahan, C. S.; McGrath, D. V.; New J. Chem. 2012, 36, 492−505. 145.de Gracia Lux, C.; McFearin, C.; Sankaranarayanan, J.; Fomina, N.; Almutairi, A.; ACS
Macro Lett. 2012, 1, 922−926.
146.Long, S.; Science 2014, 344, 706-707.
147.Kumar, K. S.; Kumar, V. B.; Paik, P.; J. of Nanoparticles 2013, 24 p.
148.Chatterjee, K.; Sarkar, S.; Rao, K. J.; Paria, S.; Advances in Colloid and Interface Science 2014, 209, 8-39.
149.Button, B.; Cai, L.-H.; Ehre, C.; Kesimer, M.; Hill, D. B.; Sheehan, J. K.; Boucher, R. C.; Rubinstein, M.; Science 2012, 337, 937–941.
151.Baos, S. C.; Phillips, D. B.; Wildling, L.; McMaster, T. J.; Berry, M.; Biophys. J. 2012, 102, 176–184.
152.Tarran, R.; Button, B.; Boucher, R. C.; Annu. Rev. Physiol. 2006, 68, 543–561.
153.Matthews, L. W.; Spector, S.; Lemm, J.; Potter, J. L.; Am. Rev. Respir. Dis. 1963, 88, 199– 204.
154.Thornton, D. J.; Sheehan, J. K.; Proc. Am. Thorac. Soc. 2004, 1, 54–61.
155.McMaster, T. J.; Berry, M.; Corfield, A. P.; Miles, M. J.; Biophys. J. 1999, 77, 533–541. 156.Round, A. N.; Berry, M.; McMaster, T. J.; Stoll, S.; Gowers, D.; Corfield, A. P.; Miles, M.
J.; Biophys. J. 2002, 83, 1661–1670.
157.Rose, M .C.; Voynow, J .A.; Physiol. Rev. 2006, 86, 245–278.
158.Berry, M.; Corfield, A. P.; McMaster, T. J.; Soft Matter 2013, 9, 1740.
159.Sharma, P.; Dudus, L.; Nielsen, P. A.; Clausen, H.; Yankaskas, J. R.; Hollingsworth, M. A.; Engelhardt, J. F.; Am. J. Respir. Cell. Mol. Biol. 1998, 19, 30–37.
160.Takeyama, K.; Dabbagh, K.; Jeong Shim, J.; Dao-Pick, T.; Ueki, I.F.; Nadel, J. A.; J. Immunol. 2000, 164,1546–1552.
161.FitzGerald, J. M.; Boulet, L. P.; McIvor, R. A.; Zimmerman, S.; Chapman, K. R.; Can. Respir. J. 2006, 13, 253-259.
162.Lemanske, R. F.; Busse, W. W.; J. Allergy Clin. Immunol. 2010, 125, S95-S102. 163.Ordonez, C. L.; Khashayar, R.; Wong, H. H.; Ferrando, R.; Wu, R.; Hyde, D. M.;
Hotchkiss, J. A.; Zhang, Y.; Novikov, A.; Dolganov, G.; Fahy, J. V.; Am. J. Respir. Crit. Care Med. 2001, 163, 517-523.
164.Murray, C. J. L.; Lopez, A. D.; Mathers, C. D.; Stein, C.; The Global Burden of Disease 2000 Project: Geneva: WHO 2001, 36.
165.National Heart, Lung and Blood Institute; NHLBI Morbidity and Mortality Chartbook, 2012. Bethseda: USDHHS 2012. (available from https://www.nhlbi.nih.gov/research/ reports/2012-mortality-chart-book; accessed January 13, 2017).
166.National Centre for Health Statistics; Vital and Health Statistics, series 10 1974-1997. 167.Penman, R. W.; O’Neill, R. P.; Begley, L.; Am. Rev. Respir. Dis. 1970, 101, 536–544.
168.Colebatch, H. J.; Finucane, K. E.; Smith, M. M.; J. Appl. Physiol. 1973, 34, 143–153.