Mucus as a barrier for biopharmaceuticals and drug delivery systems

Mucosal Delivery of Biopharmaceuticals: Biology, Challenges and Strategies

Volumn 9781461495246, Issue , 2014, Pages 59-97

  Zhang, Hongbo ^a   Shahbazi, Mohammed Ali ^a   Almeida, Patrick V ^a   Santos, Hélder A ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Drug delivery; Mucoadhesion; Mucoadhesive drug delivery systems; Mucosal barrier; Mucus; Mucus penetrating particle; Nanoparticle; Penetration; Polymer

Indexed keywords

EID: 84930021781     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-9524-6_3     Document Type: Chapter

References (188)

1. Shmulewitz A, Langer R the ascendance of combination products. Nat Biotechnol. 2006;24(3):277-80.
2. Santos HA, Bimbo LM, Lehto VP, Airaksinen AJ, Salonen J, Hirvonen J. Multifunctional porous silicon for therapeutic drug delivery and imaging. Curr Drug Discov Technol. 2011;8(3)228-49.
3. Langer R. Drug delivery and targeting. Nature. 1998;392(6679 Suppl):5-10.
4. Farokhzad OC, Langer R. Nanomedicine: developing smarter therapeutic and diagnostic modalities. Adv Drug Deliv Rev. 2006;58(14):1456-9.
5. Wong C, Stylianopoulos T, Cui J, Martin J, Chauhan VP, Jiang W, Popovic Z, Jain RK, Bawendi MG, Fukumura D. Multistage nanoparticle delivery system for deep penetration into tumor tissue. Proc Natl Acad U S A. 2011;108(6):2426-31.
6. Yuan F, Leunig M, Huang SK, Berk DA, Papahadjopoulos D, Jain RK. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res. 1994;54(13):3352-6.
7. Jiang X-M, Wang L-M, Chen C-Y. Cellular uptake, intracellular trafficking and biological responses of gold nanoparticles. J Chinese Chem Soc. 2011;58(3):273-81.
8. Chiu Y-L, Ho Y-C, Chen Y-M, Peng S-F, Ke C-J, Chen K-J, Mi F-L, Sung H-W the characteristics, cellular uptake and intracellular trafficking of nanoparticles made of hydrophobically-modified chitosan. J Control Release. 2010;146(1):152-9.
9. Tarn D, Xue M, Zink JI. pH-responsive dual cargo delivery from mesoporous silica nanoparticles with a metal-latched nanogate. Inorg Chem. 2013;52(4):2044-9.
10. Agostini A, Mondragon L, Bernardos A, Martinez-Manez R, Marcos MD, Sancenon F, Soto J, Costero A, Manguan-Garcia C, Perona R, Moreno-Torres M, Aparicio-Sanchis R, Murguia JR. Targeted cargo delivery in senescent cells using capped mesoporous silica nanoparticles. Angew Chem Int Ed Engl. 2012;51(42):10556-60.
11. Aznar E, Mondragon L, Ros-Lis JV, Sancenon F, Marcos MD, Martinez-Manez R, Soto J, Perez-Paya E, Amoros P. Finely tuned temperature-controlled cargo release using paraffincapped mesoporous silica nanoparticles. Angew Chem Int Ed Engl. 2011;50(47):11172-5.
12. Cone RA. Barrier properties of mucus. Adv Drug Deliv Rev. 2009;61(2):75-85.
13. Khutoryanskiy VV. Advances in mucoadhesion and mucoadhesive polymers. Macromol Biosci. 2011;11(6):748-64.
14. Ishida M, MachidaY, Nambu N, Nagai T. New mucosal dosage form of insulin. Chem Pharm Bull. 1981;29(3):810-6.
15. Nagai T. Adhesive topical drug delivery system. J Control Release. 1985;2:121-34.
16. Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm. 2009;71(3):505-18.
17. Bagan J, Paderni C, Termine N, Campisi G, Lo Russo L, Compilato D, Di Fede O. Mucoadhesive polymers for oral transmucosal drug delivery: a review. Curr Pharm Des. 2012;18(34):5497-514.
18. de Araujo Pereira RR, Bruschi ML. Vaginal mucoadhesive drug delivery systems. Drug Dev Ind Pharm. 2012;38(6)643-52.
19. Shinkar DM, Dhake AS, Setty CM. Drug delivery from the oral cavity: a focus on mucoadhesive buccal drug delivery systems. PDA J Pharm Sci Technol/PDA. 2012;66(5):466-500.
20. Singh RM, Kumar A, Pathak K. Mucoadhesive in situ nasal gelling drug delivery systems for modulated drug delivery. Expert Opin Drug Deliv. 2013;10(1):115-30.
21. Swain S, Behera A, Beg S, Patra CN, Dinda SC, Sruti J, Rao ME. Modified alginate beads for mucoadhesive drug delivery system: an updated review of patents. Recent Pat Drug Deliv Formul. 2012;6(3):259-77.
22. Sandri G, Rossi S, Ferrari F, Bonferoni MC, Zerrouk N, Caramella C. Mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco-2 cell lines, and rat jejunum. J Pharm Pharmacol. 2004;56(9): 1083-90.
23. Bonferoni MC, Chetoni P, Giunchedi P, Rossi S, Ferrari F, Burgalassi S, Caramella C. Carrageenan-gelatin mucoadhesive systems for ion-exchange based ophthalmic delivery: in vitro and preliminary in vivo studies. Eur J Pharm Biopharm 2004;57(3):465-72.
24. Sandri G, Rossi S, Ferrari F, Bonferoni MC, Muzzarelli C, Caramella C. Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur J Pharm Sci. 2004; 21(2-3):351-59.
25. Sandri G, Bonferoni MC, Rossi S, Ferrari F, Boselli C, Caramella C. Insulin-loaded nanoparticles based on N-Trimethyl chitosan: in vitro (Caco-2 model) and ex vivo (excised rat jejunum, duodenum, and ileum) evaluation of penetration enhancement properties. AAPS PharmSciTech. 2010;11(1):362-71.
26. Ensign LM, Schneider C, Suk JS, Cone R, Hanes J. Mucus penetrating nanoparticles: biophysical tool and method of drug and gene delivery. Adv Mater. 2012;24(28):3887-94.
27. Paderni C, Compilato D, Giannola LI, Campisi G. Oral local drug delivery and new perspectives in oral drug formulation. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114(3):e25-34.
28. Carvalho FC, Rocha e Silva H, da Luz GM, Barbi Mda S, Landgraf DS, Chiavacci LA, Sarmento VH, Gremiao MP. Rheological, mechanical and adhesive properties of surfactantcontaining systems designed as a potential platform for topical drug delivery. J Biomed Nanotechnol. 2012;8(2):280-9.
29. Gee CM, Nicolazzo JA, Watkinson AC, Finnin BC. Assessment of the lateral diffusion and penetration of topically applied drugs in humans using a novel concentric tape stripping design. Pharm Res. 2012;29(8):2035-46.
30. Fulgencio Gde O, Viana FA, Ribeiro RR, Yoshida MI, Faraco AG, Cunha-Junior Ada S. New mucoadhesive chitosan film for ophthalmic drug delivery of timolol maleate: in vivo evaluation. J Ocul Pharmacol Ther. 2012;28(4):350-8.
31. Liu J, Wang Z, Liu C, Xi H, Li C, ChenY, Sun L, Mu L, Fang L. Silicone adhesive, a better matrix for tolterodine patches-A research based on in vitro/in vivo studies. Drug Dev Ind Pharm. 2012;38(8):1008-14.
32. Mahmoud AA, El-Feky GS, Kamel R, Awad GE. Chitosan/sulfobutylether-beta-cyclodextrin nanoparticles as a potential approach for ocular drug delivery. Int J Pharm. 2011;413(1-2):229-36.
33. Movassaghian S, Barzegar-Jalali M, Alaeddini M, Hamedyazdan S, Afzalifar R, Zakeri-Milani P, Mohammadi G, Adibkia K. Development of amitriptyline buccoadhesive tablets for management of pain in dental procedures. Drug Dev Ind Pharm. 2011;37(7):849-54.
34. Al-Hezaimi K, Al-Askar M, Selamhe Z, Fu JH, Alsarra IA, Wang HL. Evaluation of novel adhesive film containing ketorolac for post-surgery pain control: a safety and efficacy study. J Periodontol. 2011;82(7):963-8.
35. Morrow DI, McCarron PA, Woolfson AD, Juzenas P, Juzeniene A, Iani V, Moan J, Donnelly RF. Novel patch-based systems for the localised delivery of ALA-esters. J Photochem Photobiol B. 2010;101(1):59-69.
36. Gullick DR, Pugh WJ, Ingram MJ, Cox PA, Moss GP. Formulation and characterization of a captopril ethyl ester drug-in-Adhesive-Type patch for percutaneous absorption. Drug Dev Ind Pharm. 2010;36(8):926-32.
37. Zhang J, Deng L, Zhao H, Liu M, Jin H, Li J, Dong A. Pressure-sensitive adhesive properties of poly(N-vinyl pyrrolidone)/D, L-lactic acid oligomer/glycerol/water blends for TDDS. J Biomater Sci Polym Ed. 2010;21(1):1-15.
38. Jones DS, Bruschi ML, de Freitas O, Gremiao MP, Lara EH, Andrews GP. Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity. Int J Pharm. 2009;372(1-2):49-58.
39. Hung CF, Lin YK, Huang ZR, Fang JY. Delivery of resveratrol, a red wine polyphenol, from solutions and hydrogels via the skin. Biol Pharm Bull. 2008;31(5):955-62.
40. Martin MD, Sherman J, van derVen P, Burgess J.A controlled trial of a dissolving oral patch concerning glycyrrhiza (licorice) herbal extract for the treatment of aphthous ulcers. Gen Dent. 2008;56(2):206-10; quiz 211-202, 224.
41. Chandrashekar NS, Hiremath SR. Transdermal delivery of 5-fluorouracil for induced ehrlich ascites carcinoma tumor in BALB/c mice and pharmacokinetic study. Recent Pat Anticancer Drug Discov. 2007;2(3):235-9.
42. Abdulmajed K, Heard CM.Topical delivery of retinyl ascorbate. 3. Influence of follicle sealing and skin stretching. Skin Pharmacol Physiol. 2008;21(1):46-9.
43. Jain AK, Chalasani KB, Khar RK, Ahmed FJ, Diwan PV. Muco-Adhesive multivesicular liposomes as an effective carrier for transmucosal insulin delivery. J Drug Target. 2007;15(6):417-27.
44. Valtcheva-Sarker RV, O'Reilly JD, Sarker DK. Administration of drug and nutritional components in nano-engineered form to increase delivery ratio and reduce current inefficient practice. Recent Pat Drug Deliv Formul. 2007;1(2):147-59.
45. Donnelly RF, McCarron PA, Zawislak AA, Woolfson AD. Design and physicochemical characterisation of a bioadhesive patch for dose-controlled topical delivery of imiquimod. Int J Pharm. 2006;307(2):318-25.
46. Barnhart K. Vaginal drug delivery. IDrugs. 1999;2(8): 756-9.
47. Jones DS, Lawlor MS, Woolfson AD. Rheological and mucoadhesive characterization of polymeric systems composed of poly(methylvinylether-co-maleic anhydride) and poly(vinylpyrrolidone), designed as platforms for topical drug delivery. J Pharm Sci. 2003;92(5):995-1007.
48. Bian S, Doh HJ, Zheng J, Kim JS, Lee CH, Kim DD. In vitro evaluation of patch formulations for topical delivery of gentisic acid in rats. Eur J Pharm Sci. 2003;18(2):141-7.
49. BaeyensV, Felt-Baeyens O, Rougier S, Pheulpin S, Boisrame B, Gurny R. Clinical evaluation of bioadhesive ophthalmic drug inserts (BODI) for the treatment of external ocular infections in dogs. J Control Release. 2002;85(1-3):163-8.
50. Artusi M, Santi P, Colombo P, Junginger HE. Buccal delivery of thiocolchicoside: in vitro and in vivo permeation studies. Int J Pharm. 2003;250(1):203-13.
51. Taware CP, Mazumdar S, Pendharkar M, Adani MH, Devarajan PV. A bioadhesive delivery system as an alternative to infiltration anesthesia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997;84(6):609-15.
52. Genta I, Conti B, Perugini P, Pavanetto F, Spadaro A, Puglisi S. Bioadhesive microspheres for ophthalmic administration of acyclovir. J Pharm Pharmacol. 1997;49(8):737-42.
53. Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest. 2002;109(5):571-7.
54. Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev. 2009;61(2):158-71.
55. Lai SK, WangYY, Hida K, Cone R, Hanes J. Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proc Natl Acad Sci U S A. 2010;107(2):598-603.
56. Lai SK, WangYY, Cone R, Wirtz D, Hanes J. Altering mucus rheology to 'solidify' human mucus at the nanoscale. PloS One. 2009;4(1):e4294.
57. Lai SK, O'Hanlon DE, Harrold S, Man ST, Wang YY, Cone R, Hanes J. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc Natl Acad Sci U S A. 2007;104(5):1482-7.
58. Lai SK, WangYY, Wirtz D, Hanes J. Micro-And macrorheology of mucus. Adv Drug Deliv Rev. 2009;61(2):86-100.
59. Samet JM, Cheng PW the role of airway mucus in pulmonary toxicology. Environ Health Perspect. 1994;102(Suppl 2):89-103.
60. Quraishi MS, Jones NS, Mason J the rheology of nasal mucus: a review. Clin Otolaryngol Allied Sci. 1998;23(5):403-13.
61. Allen A, Flemstrom G, Garner A, Kivilaakso E. Gastroduodenal mucosal protection. Physiol Rev. 1993;73(4):823-57.
62. Carlstedt I, Lindgren H, Sheehan JK, Ulmsten U, Wingerup L. Isolation and characterization of human cervical-mucus glycoproteins. Biochem J. 1983;211(1):13-22.
63. Chao CC, Butala SM, Herp A. Studies on the isolation and composition of human ocular mucin. Exp Eye Res. 1988;47(2):185-96.
64. Engel E, Guth PH, NishizakiY, Kaunitz JD. Barrier function of the gastric mucus gel. Am J Physiol. 1995;269(6 Pt 1):G994-9.
65. Wang YY, Lai SK, Suk JS, Pace A, Cone R, Hanes J. Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that 'slip' through the human mucus barrier. Angew Chem Int Ed Engl. 2008;47(50):9726-9.
66. Olmsted SS, Padgett JL, Yudin AI, Whaley KJ, Moench TR, Cone RA. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys J. 2001;81(4):1930-7.
67. Crater JS, Carrier RL. Barrier properties of gastrointestinal mucus to nanoparticle transport. Macromol Biosci. 2010;10(12):1473-83.
68. Yoncheva K, Gomez S, Campanero MA, Gamazo C, Irache JM. Bioadhesive properties of pegylated nanoparticles. Expert Opin Drug Deliv. 2005;2(2):205-18.
69. Saltzman WM, Radomsky ML, Whaley KJ, Cone RA. Antibody diffusion in human cervical mucus. Biophys J. 1994;66(2 Pt 1):508-15.
70. Corthesy B, Kraehenbuhl JP. Antibody-mediated protection of mucosal surfaces. Curr Top Microbiol Immunol. 1999;236:93-111.
71. Larhed AW, Artursson P, Grasjo J, Bjork E. Diffusion of drugs in native and purified gastrointestinal mucus. J Pharm Sci. 1997;86(6):660-5.
72. Matthes I, Nimmerfall F, Vonderscher J, Sucker H. Mucus models for investigation of intestinal absorption mechanisms. 4. Comparison of mucus models with absorption models in vivo and in situ for prediction of intestinal drug absorption. Pharmazie. 1992;47(10):787-91.
73. Kas HS. Chitosan: properties, preparations and application to microparticulate systems. J Microencapsul. 1997;14(6):689-711.
74. Dawson M, Wirtz D, Hanes J. Enhanced viscoelasticity of human cystic fibrotic sputum correlates with increasing microheterogeneity in particle transport. J Biol Chem. 2003;278(50):50393-401.
75. Thornton DJ, Sheehan JK. From mucins to mucus: toward a more coherent understanding of this essential barrier. Proc Am Thorac Soc. 2004;1(1):54-61.
76. Wolf DP, Blasco L, Khan MA, Litt M. Human cervical mucus. I. Rheologic characteristics. Fertil Steril. 1977;28(1):41-6.
77. Boucher RC, Stutts MJ, Bromberg PA, Gatzy JT. Regional differences in airway surface liquid composition. J Appl Physiol. 1981;50(3):613-20.
78. Girod S, Galabert C, Lecuire A, Zahm JM, Puchelle E. Phospholipid composition and surfaceactive properties of tracheobronchial secretions from patients with cystic fibrosis and chronic obstructive pulmonary diseases. Pediatr Pulmonol. 1992;13(1):22-7.
79. Yeates DB, Besseris GJ, Wong LB. Physicochemical properties of mucus and its propulsion. In: Crystal RG, et al. editors the lung: scientific foundations. Philadelphia: Lippincott-Raven; 1997. pp. 487-503.
80. Lamont JT. Mucus: the front line of intestinal mucosal defense. Ann N Y Acad Sci. 1992;664:190-201.
81. Lethem MI, James SL, Marriott C the role of mucous glycoproteins in the rheologic properties of cystic fibrosis sputum. Am Rev Respir Dis. 1990;142(5):1053-8.
82. Cone R. Mucus, In: Ogra PL, et al. editors. Mucosal immunology. San Diego: Academic; 1999. pp. 43-64.
83. App EM, Zayas JG, King M. Rheology of mucus and transepithelial potential difference: small airways versus trachea. Eur Respir J. 1993;6(1):67-75.
84. Rubin BK, Druce H, Ramirez OE, Palmer R. Effect of clarithromycin on nasal mucus properties in healthy subjects and in patients with purulent rhinitis. Am J Respir Crit Care Med. 1997;155(6):2018-23.
85. Rubin BK. Mucus structure and properties in cystic fibrosis. Paediatric Respir Rev. 2007;8(1):4-7.
86. VoynowJA, Gendler SJ, Rose MC. Regulation of mucin genes in chronic inflammatory airway diseases. Am J Respir Cell Mol Biol. 2006;34(6):661-5.
87. Hattori M, Majima Y, Ukai K, Sakakura Y. Effects of nasal allergen challenge on dynamic viscoelasticity of nasal mucus. Ann Otol Rhinol Laryngol. 1993;102(4 Pt 1):314-7.
88. Allen A, Cunliffe WJ, Pearson JP, Sellers LA, Ward R. Studies on gastrointestinal mucus. Scand J Gastroenterol. 1984;Supplement 93:101-13.
89. Clift AF. Early studies on the rheology of cervical mucus. Am J Obstetr Gynecol. 1979;134(7):829-32.
90. Shahbazi MA, Santos HA. Improving oral absorption via drug-loaded nanocarriers: absorption mechanisms, intestinal models and rational fabrication. Curr Drug Metab. 2013;14(1): 28-56.
91. Wood KM, Stone GM, Peppas NA the effect of complexation hydrogels on insulin transport in intestinal epithelial cell models. Acta Biomaterialia. 2010;6(1):48-56.
92. Balimane PV, Chong S, Morrison RA. Current methodologies used for evaluation of intestinal permeability and absorption. J Pharmacol Toxicol Meth. 2000;44(1):301-12.
93. Antunes F, Andrade F, Araujo F, Ferreira D, Sarmento B. Establishment of a triple co-culture in vitro cell models to study intestinal absorption of peptide drugs. Euro J Pharm Biopharm. 2013;83(3):427-35.
94. Wikman A, Karlsson J, Carlstedt I, Artursson P. A drug absorption model based on the mucus layer producing human intestinal goblet cell line HT29-H. Pharm Res. 1993;10(6): 843-52.
95. Keely S, Rullay A, Wilson C, Carmichael A, Carrington S, Corfield A, Haddleton DM, Brayden DJ. In vitro and ex vivo intestinal tissue models to measure mucoadhesion of poly (methacrylate) and N-Trimethylated chitosan polymers. Pharm Res. 2005;22(1):38-49.
96. Nollevaux G, Deville C, El Moualij B, Zorzi W, Deloyer P, Schneider YJ, Peulen O, Dandrifosse G. Development of a serum-free co-culture of human intestinal epithelium cell-lines (Caco-2/HT29-5M21). BMC Cell Biol. 2006;7:20.
97. Mahler GJ, Shuler ML, Glahn RP. Characterization of Caco-2 and HT29-MTX cocultures in an in vitro digestion/cell culture model used to predict iron bioavailability. J Nutr Biochem. 2009;20(7):494-502.
98. Gamboa JM, Leong KW. In vitro and in vivo models for the study of oral delivery of nanoparticles. Adv Drug Deliv Rev. 2013;65:800-10.
99. Barthe L, Woodley JF, Kenworthy S, Houin G. An improved everted gut sac as a simple and accurate technique to measure paracellular transport across the small intestine. Eur J Drug Metab Pharmacokinet. 1998;23:313-23.
100. Alam MA, Al-Jenoobi FI, Al-MohizeaAM. Everted gut sac model as a tool in pharmaceutical research: limitations and applications. J Pharm Pharmacol. 2012;64(3):326-36.
101. Carreno-Gomez B, Duncan R. Everted rat intestinal sacs: a new model for the quantitation of P-glycoprotein mediated-efflux of anticancer agents. Anticancer Res. 2000;20(5A):3157-61.
102. van de Kerkhof EG, de Graaf IA, Ungell AL, Groothuis GM. Induction of metabolism and transport in human intestine: validation of precision-cut slices as a tool to study induction of drug metabolism in human intestine in vitro. Drug Metab Dispos. 2008;36(3):604-13.
103. van de Kerkhof EG, de Graaf IA, Groothuis GM. In vitro methods to study intestinal drug metabolism. Curr Drug Metab. 2007;8(7):658-75.
104. Groothuis GM, de Graaf IA. Precision-cut intestinal slices as in vitro tool for studies on drug metabolism. Curr Drug Metab. 2013;14(1):112-9.
105. van Midwoud PM, Merema MT, Verpoorte E, Groothuis GM. A microfluidic approach for in vitro assessment of interorgan interactions in drug metabolism using intestinal and liver slices. Lab Chip. 2010;10(20):2778-86.
106. de Kanter R, Tuin A, van de Kerkhof E, Martignoni M, Draaisma AL, de Jager MH, de Graaf IA, Meijer DK, Groothuis GM. A new technique for preparing precision-cut slices from small intestine and colon for drug biotransformation studies. J Pharmacol Toxicol Meth. 2005;51(1):65-72.
107. Boddupalli BM, Mohammed ZN, Nath RA, Banji D. Mucoadhesive drug delivery system: an overview. J Adv Pharm Technol Res. 2010;1(4):381-7.
108. Smart JD the basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev. 2005;57(11):1556-68.
109. Derjaguin BV, Aleinikova IN, ToporovYP. On the role of electrostatic forces in the adhesion of polymer particles to solid surfaces. Progr Surf Sci. 1994;45(1-4):119-23.
110. Shaikh R, Raj Singh TR, Garland MJ, Woolfson AD, Donnelly RF. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011;3(1):89-100.
111. Gu JM, Robinson JR, Leung SH. Binding of acrylic polymers to mucin/epithelial surfaces: structure-property relationships. Crit Rev Ther Drug Carrier Syst. 1988;5(1):21-67.
112. Dodou D, Breedveld P, Wieringa PA. Mucoadhesives in the gastrointestinal tract: revisiting the literature for novel applications. Eur J Pharm Biopharm. 2005;60(1):1-16.
113. das Neves J, Amiji M, Sarmento B. Mucoadhesive nanosystems for vaginal microbicide development: friend or foe?Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2011;3(4):389-99.
114. das Neves J, Bahia MF, Amiji MM, Sarmento B. Mucoadhesiveicines: characterization and modulation of mucoadhesion at the nanoscale. Expert Opin Drug Deliv. 2011;8(8):1085-104.
115. Andrews GP, Donnelly L, Jones DS, Curran RM, Morrow RJ, Woolfson AD, Malcolm RK. Characterization of the rheological, mucoadhesive, and drug release properties of highly structured gel platforms for intravaginal drug delivery. Biomacromolecules. 2009;10(9):2427-35.
116. Gurny R, Meyer JM, Peppas NA. Bioadhesive intraoral release systems: design, testing and analysis. Biomaterials. 1984;5(6):336-40.
117. Tiwari D, Goldman D, Sause R, Madan PL. Evaluation of polyoxyethylene homopolymers for buccal bioadhesive drug delivery device formulations. AAPS PharmSci. 1999;1(3):E13.
118. McCarron PA, Woolfson AD, Donnelly RF, Andrews GP, Zawislak A, Price JH. Influence of plasticizer type and storage conditions on properties of poly(methyl vinyl ether-co-maleic anhydride) bioadhesive films. J Appl Polym Sci. 2004;91(3):1576-89.
119. Solomonidou D, Cremer K, Krumme M, Kreuter J. Effect of carbomer concentration and degree of neutralization on the mucoadhesive properties of polymer films. J Biomater Sci Polym Ed. 2001;12(11):1191-205.
120. Dhawan S, Singla AK, Sinha VR. Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods. AAPS PharmSciTech. 2004;5(4):e67.
121. Peppas NA, Buri PA. Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues. J Control Release. 1985;2:257-75.
122. Patel MM, Smart JD, Nevell TG, Ewen RJ, Eaton PJ, Tsibouklis J. Mucin/poly(acrylic acid) interactions: a spectroscopic investigation of mucoadhesion. Biomacromolecules. 2003;4(5):1184-90.
123. Nikonenko NA, Bushnak IA, Keddie JL. Spectroscopic ellipsometry of mucin layers on an amphiphilic diblock copolymer surface. Appl Spectrosc. 2009;63(8):889-98.
124. Hu L, Sun Y, Wu Y. Advances in chitosan-based drug delivery vehicles. Nanoscale 2013;5(8):3103-11.
125. Sarmento B, das Neves J, editors. Chitosan-based systems for biopharmaceuticals: delivery, targeting and polymer therapeutics. 1st ed.Wiley; 2012.
126. Andrade F, Antunes F, Nascimento AV, da Silva SB, das Neves J, Ferreira D, Sarmento B. Chitosan formulations as carriers for therapeutic proteins. Curr Drug Discov Tech. 2011;8(3):157-72.
127. Bernkop-Schnurch A. Thiomers: a new generation of mucoadhesive polymers. Adv Drug Deliv Rev. 2005;57(11):1569-82.
128. Laffleur F, Bernkop-Schnurch A. Thiomers: promising platform for macromolecular drug delivery. Future Med Chem. 2012;4(17):2205-16.
129. Guggi D, Marschutz MK, Bernkop-SchnurchA. Matrix tablets based on thiolated poly(acrylic acid): pH-dependent variation in disintegration and mucoadhesion. Int J Pharm. 2004;274 (1-2):97-105.
130. Schmitz T, Grabovac V, Palmberger TF, Hoffer MH, Bernkop-Schnurch A. Synthesis and characterization of a chitosan-N-Acetyl cysteine conjugate. Int J Pharm. 2008;347(1-2): 79-85.
131. Nema T, Jain A, Shilpi S, Gulbake A, Hurkat P, Jain SK. Insulin delivery through nasal route using thiolated microspheres. Drug Deliv. 2013;20(5):210-5.
132. Wang J, Tabata Y, Bi D, Morimoto K. Evaluation of gastric mucoadhesive properties of aminated gelatin microspheres. J Control Release. 2001;73(2-3):223-31.
133. Thanou M, Nihot MT, Jansen M, Verhoef JC, Junginger HE. Mono-N-carboxymethyl chitosan (MCC), a polyampholytic chitosan derivative, enhances the intestinal absorption of low molecular weight heparin across intestinal epithelia in vitro and in vivo. J Pharm Sci. 2001;90(1):38-46.
134. Tripathi P, Beaussart A, Alsteens D, DupresV, Claes I, von Ossowski I, deVos WM, Palva A, Lebeer S, Vanderleyden J, DufreneYF.Adhesion and nanomechanics of pili from the probiotic Lactobacillus rhamnosus GG. ACS Nano. 2013;7(4):3685-97.
135. Vandamme TF, Brobeck L. Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release. 2005;102(1):23-38.
136. Ivanov AE, Nilsson L, Galaev IY, Mattiasson B. Boronate-containing polymers form affinity complexes with mucin and enable tight and reversible occlusion of mucosal lumen by poly(vinyl alcohol) gel. Int J Pharm. 2008;358(1-2):36-43.
137. Perioli L, Ambrogi V, Giovagnoli S, Blasi P, Mancini A, Ricci M, Rossi C. Influence of compression force on the behavior of mucoadhesive buccal tablets. AAPS PharmSciTech. 2008;9(1):274-81.
138. Shemer A, Amichai B, Trau H, Nathansohn N, Mizrahi B, Domb AJ. Efficacy of a mucoadhesive patch compared with an oral solution for treatment of aphthous stomatitis. Drugs R D. 2008;9(1):29-35.
139. Donnelly RF, McCarron PA, Tunney MM, David Woolfson A. Potential of photodynamic therapy in treatment of fungal infections of the mouth. Design and characterisation of a mucoadhesive patch containing toluidine blue O. J Photochem Photobiol B. 2007;86(1): 59-69.
140. Modi P, Mihic M, Lewin A the evolving role of oral insulin in the treatment of diabetes using a novel RapidMist System. Diabetes Metab Res Rev. 2002;18(1):S38-42.
141. Chaturvedi M, Kumar M, Pathak K. A review on mucoadhesive polymer used in nasal drug delivery system. J Adv Pharm Technol Res. 2011;2(4):215-22.
142. McInnes FJ, O'Mahony B, Lindsay B, Band J, Wilson CG, Hodges LA, Stevens HN. Nasal residence of insulin containing lyophilised nasal insert formulations, using gamma scintigraphy. Eur J Pharm Sci. 2007;31(1):25-31.
143. Coucke D, Schotsaert M, Libert C, Pringels E, Vervaet C, Foreman P, Saelens X, Remon JP. Spray-dried powders of starch and crosslinked poly(acrylic acid) as carriers for nasal delivery of inactivated influenza vaccine. Vaccine. 2009;27(8):1279-86.
144. Sensoy D, Cevher E, SariciA, Yilmaz M, OzdamarA, Bergisadi N. Bioadhesive sulfacetamide sodium microspheres: evaluation of their effectiveness in the treatment of bacterial keratitis caused by Staphylococcus aureus and Pseudomonas aeruginosa in a rabbit model. Eur J Pharm Biopharm. 2009;72(3):487-95.
145. de la Fuente M, Seijo B, Alonso MJ. Bioadhesive hyaluronan-chitosan nanoparticles can transport genes across the ocular mucosa and transfect ocular tissue. Gene Ther. 2008;15(9):668-76.
146. Varum FJ, McConnell EL, Sousa JJ, Veiga F, BasitAW. Mucoadhesion and the gastrointestinal tract. Crit Rev Ther Drug Carrier Syst. 2008;25(3):207-58.
147. Ahmed IS, Ayres JW. Bioavailability of riboflavin from a gastric retention formulation. Int J Pharm. 2007;330(1-2):146-54.
148. Rodes L, Coussa-Charley M, Marinescu D, Paul A, Fakhoury M, Abbasi S, Khan A, Tomaro-Duchesneau C, Prakash S. Design of a novel gut bacterial adhesion model for probiotic applications. Artif Cells Nanomed Biotechnol. 2013;41(2):116-24.
149. Chen S, CaoY, Ferguson LR, Shu Q, Garg S. Evaluation of mucoadhesive coatings of chitosan and thiolated chitosan for the colonic delivery of microencapsulated probiotic bacteria. J Microencapsul. 2013;30(2):103-15.
150. El-Leithy ES, Shaker DS, Ghorab MK, Abdel-Rashid RS. Evaluation of mucoadhesive hydrogels loaded with diclofenac sodium-chitosan microspheres for rectal administration. AAPS PharmSciTech. 2010;11(4):1695-702.
151. Bassi P, Kaur G. Innovations in bioadhesive vaginal drug delivery system. Expert Opin Ther Pat. 2012;22(9):1019-32.
152. Pereira RR, Ribeiro Godoy JS, Stivalet Svidzinski TI, Bruschi ML. Preparation and characterization of mucoadhesive thermoresponsive systems containing propolis for the treatment of vulvovaginal candidiasis. J Pharm Sci. 2013;102(4):1222-34.
153. Khanvilkar K, Donovan MD, Flanagan DR. Drug transfer through mucus. Adv Drug Deliv Rev. 2001;48(2-3):173-93.
154. Norris DA, Sinko PJ. Effect of size, surface charge, and hydrophobicity on the translocation of polystyrene microspheres through gastrointestinal mucin. J Appl Polym Sci. 1997;63: 1481-92.
155. Norris DA, Puri N, Labib ME, Sinko PJ. Determining the absolute surface hydrophobicity of microparticulates using thin layer wicking. J Control Release. 1999;59(2):173-85.
156. Shen H, Hu Y, Saltzman WM. DNA diffusion in mucus: effect of size, topology of DNAs, and transfection reagents. Biophys J. 2006;91(2):639-44.
157. Ribbeck K. Do viruses use vectors to penetrate mucus barriers?. Biosci Hypotheses. 2009;2(6):329-62.
158. Yuan H, Chen CY, Chai GH, Du YZ, Hu FQ. Improved transport and absorption through gastrointestinal tract by PEGylated solid lipid nanoparticles. Mol Pharmaceutics. 2013;10(5):1865-73.
159. Tang BC, Dawson M, Lai SK, Wang YY, Suk JS, Yang M, Zeitlin P, Boyle MP, Fu J, Hanes J. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci U S A. 2009;106(46):19268-73.
160. Ferrari S, Kitson C, Farley R, Steel R, Marriott C, ParkinsDA, Scarpa M, Wainwright B, Evans MJ, Colledge WH, Geddes DM, Alton EW. Mucus altering agents as adjuncts for nonviral gene transfer to airway epithelium. Gene Ther. 2001;8(18):1380-6.
161. Mert O, Lai SK, Ensign L, Yang M, WangYY, Wood J, Hanes J.Apoly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles. J Control Release. 2012;157(3):455-60.
162. Ensign LM, Tang BC, Wang YY, Tse TA, Hoen T, Cone R, Hanes J. Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci Transl Med. 2012;4(138):138ra179.
163. Suk JS, Boylan NJ, Trehan K, Tang BC, Schneider CS, Lin JM, Boyle MP, Zeitlin PL, Lai SK, Cooper MJ, Hanes J. N-Acetylcysteine enhances cystic fibrosis sputum penetration and airway gene transfer by highly compacted DNA nanoparticles. Mol Ther. 2011;19(11):1981-9.
164. Boylan NJ, Suk JS, Lai SK, Jelinek R, Boyle MP, Cooper MJ, Hanes J. Highly compacted DNA nanoparticles with low MW PEG coatings: in vitro, ex vivo and in vivo evaluation. J Control Release. 2012;157(1):72-9.
165. Collnot EM, Ali H, Lehr CM. Nano-And microparticulate drug carriers for targeting of the inflamed intestinal mucosa. J Control Release. 2012;161(2):235-46.
166. Siegmund B. Targeted therapies in inflammatory bowel disease. Dig Dis. 2009;27(4):465-9.
167. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet. 2007;369(9573):1627-40.
168. Lakatos PL. Recent trends in the epidemiology of inflammatory bowel diseases: up or down?. World J Gastroenterol. 2006;12(38):6102-8.
169. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307-17.
170. Zhou SY, Fleisher D, Pao LH, Li C, Winward B, Zimmermann EM. Intestinal metabolism and transport of 5-Aminosalicylate. Drug Metab Dispos. 1999;27(4):479-85.
171. Nakase H, Okazaki K, TabataY, Uose S, Ohana M, Uchida K, MatsushimaY, Kawanami C, Oshima C, IkadaY, Chiba T. Development of an oral drug delivery system targeting immuneregulating cells in experimental inflammatory bowel disease: a new therapeutic strategy. J Pharmacol Exp Ther. 2000;292(1):15-21.
172. Mladenovska K, Raicki RS, Janevik EI, Ristoski T, Pavlova MJ, Kavrakovski Z, Dodov MG, Goracinova K. Colon-specific delivery of 5-Aminosalicylic acid from chitosan-Ca-Alginate microparticles. Int J Pharm. 2007;342(1-2):124-36.
173. Lamprecht A, Yamamoto H, Takeuchi H, KawashimaY. Design of pH-sensitive microspheres for the colonic delivery of the immunosuppressive drug tacrolimus. Eur J Pharm Biopharm. 2004;58(1):37-43.
174. Lamprecht A, Ubrich N, Yamamoto H, Schafer U, Takeuchi H, Lehr CM, Maincent P, Kawashima. Design of rolipram-loaded nanoparticles: comparison of two preparation methods. J Control Release. 2001;71(3):297-306.
175. Lamprecht A, Yamamoto H, Takeuchi H, KawashimaY. A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles. J Control Release. 2005;104(2): 337-46.
176. Makhlof A, TozukaY, Takeuchi H. pH-sensitive nanospheres for colon-specific drug delivery in experimentally induced colitis rat model. Eur J Pharm Biopharm. 2009;72(1):1-8.
177. Pertuit D, Moulari B, Betz T, Nadaradjane A, Neumann D, Ismaili L, Refouvelet B, Pellequer Y, Lamprecht A. 5-Amino salicylic acid bound nanoparticles for the therapy of inflammatory bowel disease. J Control Release. 2007;123(3):211-8.
178. Jubeh TT, Nadler-Milbauer M, Barenholz Y, Rubinstein A. Local treatment of experimental colitis in the rat by negatively charged liposomes of catalase, TMN and SOD. J Drug Target. 2006;14(3):155-63.
179. Tirosh B, Khatib N, Barenholz Y, Nissan A, Rubinstein A. Transferrin as a luminal target for negatively charged liposomes in the inflamed colonic mucosa. Mol Pharm. 2009;6(4): 1083-91.
180. Serpe L, Canaparo R, Daperno M, Sostegni R, Martinasso G, Muntoni E, Ippolito L, Vivenza N, Pera A, Eandi M, Gasco MR, Zara GP. Solid lipid nanoparticles as anti-inflammatory drug delivery system in a human inflammatory bowel disease whole-blood model. Eur J Pharm Sci. 2010;39(5):428-36.
181. Bhol KC, Schechter PJ. Effects of nanocrystalline silver (NPI 32101) in a rat model of ulcerative colitis. Dig Dis Sci. 2007;52(10):2732-42.
182. Ensign LM, Cone R, Hanes J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv Drug Deliv Rev. 2012;64(6):557-70.
183. Owen DA, Reid PE. Histochemical alterations of mucin in normal colon, inflammatory bowel disease and colonic adenocarcinoma. Histochem J. 1995;27(11):882-9.
184. Corfield AP, Carroll D, Myerscough N, Probert CS. Mucins in the gastrointestinal tract in health and disease. Front Biosci. 2001;6:D1321-57.
185. Shirazi T, Longman RJ, Corfield AP, Probert CS. Mucins and inflammatory bowel disease. Postgrad Med J. 2000;76(898):473-8.
186. Stremmel W, Braun A, Hanemann A, Ehehalt R, Autschbach F, Karner M. Delayed release phosphatidylcholine in chronic-Active ulcerative colitis: a randomized, double-blinded, dose finding study. J Clin Gastroenterol. 2010;44(5):e101-7.
187. des Rieux A, Fievez V, Garinot M, Schneider Y-J, Preat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2006;116:1-27.
188. Wang X, ShahAA, Campbell RB, WanKT. Glycoprotein mucin molecular brush on cancer cell surface acting as mechanical barrier against drug delivery. Appl Phys Lett. 2010;97:26370.