Skip to main content

Current Status and Perspectives in Mucosal Drug Delivery of Nanotherapeutic Systems

  • Chapter
  • First Online:
  • 701 Accesses

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 41))

Abstract

Currently, nanoparticulate therapeutic systems are gaining importance and are capable of being delivered through various routes of administration while facilitating both systemic and local drug delivery. Delivering therapeutics to mucosal surfaces of various regions in the body is of special interest because it provides the ability to treat a wide range of disorders. However, due to the mucosal barriers encountered at respective organs/body cavities, it is challenging to deliver therapeutics to mucosal area. Hence, drugs demand certain carrier systems to overcome the barrier and facilitate drug delivery to the site of action. There are several strategies which enable efficient mucosal delivery of nanoparticles (NPs) and enhance the residence time of those systems at the mucosal site. Even though numerous approaches have been used with nanoparticle delivery systems, currently available strategies require further improvements to accomplish mucosal drug delivery. There is still a large gap in understanding the correlation between mucus clearance rates and NPs’ performance. This chapter summarizes various approaches utilized for enhancing mucosal delivery of nanoparticulate systems and strategies to evade mucus clearance.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Rosen H, Abribat T. The rise and rise of drug delivery. Nat Rev Drug Discov. 2005 May;4(5):381–5.

    Article  CAS  PubMed  Google Scholar 

  2. Shmulewitz A, Langer R, Patton J. Convergence in biomedical technology. Nat Biotechnol. 2006 Mar;24(3):277.

    PubMed  Google Scholar 

  3. Vaidya B, Parvathaneni V, Kulkarni NS, Shukla SK, Damon JK, Sarode A, et al. Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer. Int J Biol Macromol. 2019 Feb;122:338–47.

    Article  CAS  PubMed  Google Scholar 

  4. Kulkarni NS, Parvathaneni V, Shukla SK, Barasa L, Perron JC, Yoganathan S, et al. Tyrosine kinase inhibitor conjugated quantum dots for non-small cell lung cancer (NSCLC) treatment. Eur J Pharm Sci. 2019 May 15;133:145–59.

    Article  CAS  PubMed  Google Scholar 

  5. Rizvi SAA, Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J SPJ Off Publ Saudi Pharm Soc. 2018 Jan;26(1):64–70.

    Google Scholar 

  6. Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest. 2002 Mar 1;109(5):571–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Lee BK, Yun YH, Park K. Smart nanoparticles for drug delivery: boundaries and opportunities. Chem Eng Sci. 2015 Mar 24;125:158–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. das Neves J, Sarmento B. Technological strategies to overcome the mucus barrier in mucosal drug delivery. Adv Drug Deliv Rev. 2018 Jan 15;124:1–2.

    Article  CAS  PubMed  Google Scholar 

  9. Lai SK, Wang Y-Y, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev. 2009 Feb 27;61(2):158–71.

    Article  CAS  PubMed  Google Scholar 

  10. Hearnden V, Sankar V, Hull K, Juras DV, Greenberg M, Kerr AR, et al. New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Adv Drug Deliv Rev. 2012 Jan 1;64(1):16–28.

    Article  CAS  PubMed  Google Scholar 

  11. Roy S, Pal K, Anis A, Pramanik K, Prabhakar B. Polymers in mucoadhesive drug-delivery systems: a brief note. Des Monomers Polym. 2009 Jan 1;12(6):483–95.

    Article  CAS  Google Scholar 

  12. Tandel H. A systematic review on mucoadhesive drug delivery system. World J Pharm Res. 2017 Sep;1:337–66.

    Article  CAS  Google Scholar 

  13. Nordgård CT, Draget KI. Co association of mucus modulating agents and nanoparticles for mucosal drug delivery. Adv Drug Deliv Rev. 2018 Jan 15;124:175–83.

    Article  CAS  PubMed  Google Scholar 

  14. Menzel C, Bernkop-Schnürch A. Enzyme decorated drug carriers: targeted swords to cleave and overcome the mucus barrier. Adv Drug Deliv Rev. 2018 Jan 15;124:164–74.

    Article  CAS  PubMed  Google Scholar 

  15. Khutoryanskiy VV. Advances in mucoadhesion and mucoadhesive polymers. Macromol Biosci. 2011 Jun 14;11(6):748–64.

    Article  CAS  PubMed  Google Scholar 

  16. Kharenko EA, Larionova NI, Demina NB. Mucoadhesive drug delivery systems (review). Pharm Chem J. 2009;43:200–8.

    Article  CAS  Google Scholar 

  17. Vinod KR, Rohit Reddy T, Sandhya S, Banji D, Venkatram RB. Critical review on mucoadhesive drug delivery systems. Hygeia J Drugs Med. 2012;4(1):7–28.

    CAS  Google Scholar 

  18. Madan J, Sagar B, Mahesh D. Mucosal drug delivery system. Int J Res Ayurveda Pharm. 2010;1(1):63–70.

    CAS  Google Scholar 

  19. Yun Y, Cho YW, Park K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv Drug Deliv Rev. 2013 Jun 15;65(6):822–32.

    Article  CAS  PubMed  Google Scholar 

  20. Mahajan P, Kaur A, Aggarwal G, Sl H. Mucoadhesive drug delivery system: a review. Int J Drug Dev Res. 2013 Mar 1;5:11–20.

    CAS  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. Huang Y, Leobandung W, Foss A, Peppas NA. Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces. J Control Release Off J Control Release Soc. 2000 Mar 1;65(1–2):63–71.

    Article  CAS  Google Scholar 

  23. 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.

    CAS  PubMed  Google Scholar 

  24. Peppas NA, Buri PA. Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues. J Control Release. 1985 Nov 1;2:257–75.

    Article  CAS  Google Scholar 

  25. Ways TMM, Lau WM, Khutoryanskiy VV. Chitosan and its derivatives for application in mucoadhesive drug delivery systems. Polymers. 2018 Mar;10(3):267.

    Article  CAS  Google Scholar 

  26. Kassem MAA, ElMeshad AN, Fares AR. Lyophilized sustained release Mucoadhesive chitosan sponges for buccal Buspirone hydrochloride delivery: formulation and in vitro evaluation. AAPS PharmSciTech. 2014 Nov 6;16(3):537–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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 Feb 1;12:1191–205.

    Article  CAS  PubMed  Google Scholar 

  28. Birudaraj R, Mahalingam R, Li X, Jasti BR. Advances in buccal drug delivery. Crit Rev Ther Drug Carrier Syst. 2005;22(3):295–330.

    Article  CAS  PubMed  Google Scholar 

  29. Lee JW, Park JH, Robinson JR. Bioadhesive-based dosage forms: the next generation. J Pharm Sci. 2000 Jul;89(7):850–66.

    Article  CAS  PubMed  Google Scholar 

  30. Kumar K, Dhawan N, Sharma H, Vaidya S, Vaidya B. Bioadhesive polymers: novel tool for drug delivery. Artif Cells Nanomedicine Biotechnol. 2014 Aug 1;42(4):274–83.

    Article  CAS  Google Scholar 

  31. Nikalje A, Pratima, Tiwari S, Kamble S, Anna P, Nikalje. Mucoadhesive: as oral controlled gastroretentive drug delivery system. 2012 Sep 1;22:32–59.

    Google Scholar 

  32. Singh R, Deepak S, Garg R. Review on mucoadhesive drug delivery system with special emphasis on buccal route: an important tool in designing of novel controlled drug delivery system for the effective delivery of pharmaceuticals. J Dev Drugs. 2017 Mar 20;6:1–12.

    Google Scholar 

  33. Woodley J. Bioadhesion: new possibilities for drug administration? Clin Pharmacokinet. 2001;40(2):77–84.

    Article  CAS  PubMed  Google Scholar 

  34. Yu T, Choi W-J, Anonuevo A, Chisholm J, Pulicare S, Zhong W, et al. Mucus-penetrating nanosuspensions for enhanced delivery of poorly soluble drugs to mucosal surfaces. Adv Healthc Mater. 2016 Nov;5(21):2745–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Nance EA, Woodworth GF, Sailor KA, Shih T-Y, Xu Q, Swaminathan G, et al. A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue. Sci Transl Med. 2012 Aug 29;4(149):149ra119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Aljayyoussi G, Abdulkarim M, Griffiths P, Gumbleton M. Pharmaceutical nanoparticles and the mucin biopolymer barrier. BioImpacts BI. 2012;2(4):173–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Liu M, Zhang J, Shan W, Huang Y. Developments of mucus penetrating nanoparticles. Asian J Pharm Sci. 2015 Jul 1;10(4):275–82.

    Article  Google Scholar 

  38. Wang Y-Y, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Wang X, Fu L, Lin W, Zhang W, Pei Q, Zheng X, et al. Vaginal delivery of mucus-penetrating organic nanoparticles for photothermal therapy against cervical intraepithelial neoplasia in mice. J Mater Chem B. 2019 Jul 25;7(29):4528–37.

    Article  CAS  Google Scholar 

  40. Azarmi S, Roa WH, Löbenberg R. Targeted delivery of nanoparticles for the treatment of lung diseases. Adv Drug Deliv Rev. 2008 May 22;60(8):863–75.

    Article  CAS  PubMed  Google Scholar 

  41. Esmaeili F, Ghahremani MH, Esmaeili B, Khoshayand MR, Atyabi F, Dinarvand R. PLGA nanoparticles of different surface properties: preparation and evaluation of their body distribution. Int J Pharm. 2008 Feb 12;349(1–2):249–55.

    Article  CAS  PubMed  Google Scholar 

  42. Cu Y, Saltzman WM. Controlled surface modification with poly(ethylene)glycol enhances diffusion of PLGA nanoparticles in human cervical mucus. Mol Pharm. 2009;6(1):173–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Liu M, Zhang J, Shan W, Huang Y. Developments of mucus penetrating nanoparticles. Asian J Pharm Sci. 2015 Jul 1;10(4):275–82.

    Article  Google Scholar 

  44. Tang BC, Dawson M, Lai SK, Wang Y-Y, Suk JS, Yang M, et al. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci. 2009 Nov 17;106(46):19268–73.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Suk JS, Kim AJ, Trehan K, Schneider CS, Cebotaru L, Woodward OM, et al. Lung gene therapy with highly compacted DNA nanoparticles that overcome the mucus barrier. J Control Release Off J Control Release Soc. 2014 Mar 28;178:8–17.

    Article  CAS  Google Scholar 

  46. Boylan NJ, Suk JS, Lai SK, Jelinek R, Boyle MP, Cooper MJ, et al. Highly compacted DNA nanoparticles with low MW PEG coatings: in vitro, ex vivo and in vivo evaluation. J Control Release. 2012 Jan 10;157(1):72–9.

    Article  CAS  PubMed  Google Scholar 

  47. Kabanov AV, Batrakova EV, Alakhov VY. Pluronic block copolymers as novel polymer therapeutics for drug and gene delivery. J Control Release Off J Control Release Soc. 2002 Aug 21;82(2–3):189–212.

    Article  CAS  Google Scholar 

  48. Yang M, Lai SK, Wang Y-Y, Zhong W, Happe C, Zhang M, et al. Biodegradable nanoparticles composed entirely of safe materials that rapidly penetrate human mucus. Angew Chem Int Ed Engl. 2011 Mar 7;50(11):2597–600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Saltzman WM, Radomsky ML, Whaley KJ, Cone RA. Antibody diffusion in human cervical mucus. Biophys J. 1994 Feb;66(2 Pt 1):508–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mall MA. Unplugging mucus in cystic fibrosis and chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2016 Apr 1;13(Supplement_2):177–85.

    Google Scholar 

  51. Lai SK, Hida K, Man ST, Chen C, Machamer C, Schroer TA, et al. Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway. Biomaterials. 2007 Jun;28(18):2876–84.

    Article  CAS  PubMed  Google Scholar 

  52. McGuckin MA, Thornton DJ, Whitsett JA. Chapter 14 – Mucins and Mucus. In: Mestecky J, Strober W, Russell MW, Kelsall BL, Cheroutre H, Lambrecht BN, editors. Mucosal Immunology. Fourth ed. Boston: Academic; 2015. p. 231–50.

    Chapter  Google Scholar 

  53. Duncan GA, Jung J, Joseph A, Thaxton AL, West NE, Boyle MP, et al. Microstructural alterations of sputum in cystic fibrosis lung disease. JCI Insight. 2016 03;1(18):e88198.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Hill DB, Vasquez PA, Mellnik J, McKinley SA, Vose A, Mu F, et al. A biophysical basis for mucus solids concentration as a candidate biomarker for airways disease. PLoS One. 2014 Feb 18;9(2):e87681.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nordgård CT, Nonstad U, Olderøy MØ, Espevik T, Draget KI. Alterations in mucus barrier function and matrix structure induced by guluronate oligomers. Biomacromolecules. 2014 Jun 9;15(6):2294–300.

    Article  CAS  PubMed  Google Scholar 

  56. Pritchard MF, Powell LC, Menzies GE, Lewis PD, Hawkins K, Wright C, et al. A new class of safe oligosaccharide polymer therapy to modify the mucus barrier of chronic respiratory disease. Mol Pharm. 2016 Mar 7;13(3):863–72.

    Article  CAS  PubMed  Google Scholar 

  57. Agrahari V, Hiremath P. Challenges associated and approaches for successful translation of nanomedicines into commercial products. Nanomed. 2017 Mar 24;12(8):819–23.

    Article  CAS  Google Scholar 

  58. Bukstein DA, Luskin AT. Pharmacoeconomics of biologic therapy. Immunol Allergy Clin N Am. 2017;37(2):413–30.

    Article  Google Scholar 

  59. Chen EY, Daley D, Wang Y-C, Garnica M, Chen C-S, Chin W-C. Functionalized carboxyl nanoparticles enhance mucus dispersion and hydration. Sci Rep. 2012;2:211.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Takatsuka S, Morita T, Horikiri Y, Yamahara H, Saji H. Absorption enhancement of poorly absorbed hydrophilic compounds from various mucosal sites by combination of mucolytic agent and non-ionic surfactant. Int J Pharm. 2007 Jul 1;338:87–93.

    Article  CAS  PubMed  Google Scholar 

  61. Takatsuka S, Morita T, Horikiri Y, Yamahara H, Saji H. Influence of various combinations of mucolytic agent and non-ionic surfactant on intestinal absorption of poorly absorbed hydrophilic compounds. Int J Pharm. 2008 Feb 12;349(1–2):94–100.

    Article  CAS  PubMed  Google Scholar 

  62. Broughton-Head VJ, Smith JR, Shur J, Shute JK. Actin limits enhancement of nanoparticle diffusion through cystic fibrosis sputum by mucolytics. Pulm Pharmacol Ther. 2007;20(6):708–17.

    Article  CAS  PubMed  Google Scholar 

  63. Suk JS, Lai SK, Boylan NJ, Dawson MR, Boyle MP, Hanes J. Rapid transport of muco-inert nanoparticles in cystic fibrosis sputum treated with N-acetyl cysteine. Nanomed. 2011 Feb 1;6(2):365–75.

    Article  CAS  Google Scholar 

  64. Rubin BK. Mucus structure and properties in cystic fibrosis. Paediatr Respir Rev. 2007 Mar 1;8(1):4–7.

    Article  PubMed  Google Scholar 

  65. Lai SK, Wang Y-Y, Wirtz D, Hanes J. Micro- and macrorheology of mucus. Adv Drug Deliv Rev. 2009 Feb 27;61(2):86–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Sheffner AL, Medler EM, Jacobs LW, Sarett HP. The in vitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine. Am Rev Respir Dis. 1964 Nov;90:721–9.

    CAS  PubMed  Google Scholar 

  67. Gallon AM. Evaluation of nebulised acetylcysteine and normal saline in the treatment of sputum retention following thoracotomy. Thorax. 1996 Apr;51(4):429–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. App EM, Baran D, Dab I, Malfroot A, Coffiner M, Vanderbist F, et al. Dose-finding and 24-h monitoring for efficacy and safety of aerosolized nacystelyn in cystic fibrosis. Eur Respir J. 2002 Feb 1;19(2):294–302.

    Article  CAS  PubMed  Google Scholar 

  69. Anderson WH, Coakley RD, Button B, Henderson AG, Zeman KL, Alexis NE, et al. The relationship of mucus concentration (hydration) to mucus osmotic pressure and transport in chronic bronchitis. Am J Respir Crit Care Med. 2015 Apr 24;192(2):182–90.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Henderson AG, Ehre C, Button B, Abdullah LH, Cai L-H, Leigh MW, et al. Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressure. J Clin Invest. 2014 Jul 1;124(7):3047–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ibrahim BM, Park S, Han B, Yeo Y. A strategy to deliver genes to cystic fibrosis lungs: a battle with environment. J Control Release. 2011 Oct 30;155(2):289–95.

    Article  CAS  PubMed  Google Scholar 

  72. Blackmon RL, Kreda SM, Sears PR, Chapman BS, Hill DB, Tracy JB, et al. Direct monitoring of pulmonary disease treatment biomarkers using plasmonic gold nanorods with diffusion-sensitive OCT. Nanoscale. 2017 Apr 13;9(15):4907–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Flume PA, Aitken ML, Bilton D, Agent P, Charlton B, Forster E, et al. Optimising inhaled mannitol for cystic fibrosis in an adult population. Breathe. 2015 Mar;11(1):39–48.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Ensign LM, Hoen TE, Maisel K, Cone RA, Hanes JS. Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake. Biomaterials. 2013 Sep;34(28):6922–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mueller C, Leithner K, Hauptstein S, Hintzen F, Salvenmoser W, Bernkop-Schnürch A. Preparation and characterization of mucus-penetrating papain/poly(acrylic acid) nanoparticles for oral drug delivery applications. J Nanopart Res. 2012 Dec;1:15.

    Google Scholar 

  76. Mahmood A, Laffleur F, Leonaviciute G, Bernkop-Schnürch A. Protease-functionalized mucus penetrating microparticles: in-vivo evidence for their potential. Int J Pharm. 2017 Oct 30;532(1):177–84.

    Article  CAS  PubMed  Google Scholar 

  77. Leichner C, Menzel C, Laffleur F, Bernkop-Schnürch A. Development and in vitro characterization of a papain loaded mucolytic self-emulsifying drug delivery system (SEDDS). Int J Pharm. 2017 Sep 15;530(1):346–53.

    Article  CAS  PubMed  Google Scholar 

  78. Efiana NA, Phan TNQ, Wicaksono AJ. Bernkop- Schnürch A. Mucus permeating self-emulsifying drug delivery systems (SEDDS): About the impact of mucolytic enzymes. Colloids Surf B Biointerfaces. 2018 Jan 1;161:228–35.

    Article  CAS  PubMed  Google Scholar 

  79. Crater JS, Carrier RL. Barrier properties of gastrointestinal mucus to nanoparticle transport. Macromol Biosci. 2010 Dec 8;10(12):1473–83.

    Article  CAS  PubMed  Google Scholar 

  80. Laffleur F, Hintzen F, Shahnaz G, Rahmat D, Leithner K, Bernkop-Schnürch A. Development and in vitro evaluation of slippery nanoparticles for enhanced diffusion through native mucus. Nanomed. 2014 Mar;9(3):387–96.

    Article  CAS  Google Scholar 

  81. Dautzenberg H, Hartmann J, Grunewald S, Brand F. Stoichiometry and structure of polyelectrolyte complex particles in diluted solutions. Berichte Bunsenges Für Phys Chem. 1996;100(6):1024–32.

    Article  CAS  Google Scholar 

  82. Mottais A, Le Gall T, Sibiril Y, Ravel J, Laurent V, d’Arbonneau F, et al. Enhancement of lung gene delivery after aerosol: a new strategy using non-viral complexes with antibacterial properties. Biosci Rep. 2017 Dec 22;37(6):BSR20160618.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhou H, Fan Z, Deng J, Lemons PK, Arhontoulis DC, Bowne WB, et al. Hyaluronidase embedded in Nanocarrier PEG Shell for enhanced tumor penetration and highly efficient antitumor efficacy. Nano Lett. 2016 May 11;16(5):3268–77.

    Article  CAS  PubMed  Google Scholar 

  84. 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(11):1481–92.

    Article  CAS  Google Scholar 

  85. Groo A-C, Lagarce F. Mucus models to evaluate nanomedicines for diffusion. Drug Discov Today. 2014 Aug;19(8):1097–108.

    Article  CAS  PubMed  Google Scholar 

  86. Shen H, Hu Y, Saltzman WM. DNA diffusion in mucus: effect of size, topology of DNAs, and transfection reagents. Biophys J. 2006 Jul 15;91(2):639–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Suh J, Dawson M, Hanes J. Real-time multiple-particle tracking: applications to drug and gene delivery. Adv Drug Deliv Rev. 2005 Jan 2;57(1):63–78.

    Article  CAS  PubMed  Google Scholar 

  88. Lai S, Hanes J. Real-time multiple particle tracking of gene nanocarriers in complex biological environments. Methods Mol Biol Clifton NJ. 2008 Feb 1;434:81–97.

    CAS  Google Scholar 

  89. Dünnhaupt S, Barthelmes J, Hombach J, Sakloetsakun D, Arkhipova V, Bernkop-Schnürch A. Distribution of thiolated mucoadhesive nanoparticles on intestinal mucosa. Int J Pharm. 2011 Apr 15;408(1–2):191–9.

    Article  CAS  PubMed  Google Scholar 

  90. Gradauer K, Barthelmes J, Vonach C, Almer G, Mangge H, Teubl B, et al. Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats. J Control Release. 2013 Dec 28;172(3):872–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Suk JS, Suh J, Lai SK, Hanes J. Quantifying the intracellular transport of viral and nonviral gene vectors in primary neurons. Exp Biol Med Maywood NJ. 2007 Mar;232(3):461–9.

    CAS  Google Scholar 

  92. Boegh M, Foged C, Müllertz A, Nielsen H. Mucosal drug delivery: barriers, in vitro models and formulation strategies. J Drug Deliv Sci Technol. 2013 Dec 31;23:383–91.

    Article  CAS  Google Scholar 

  93. Behrens I, Stenberg P, Artursson P, Kissel T. Transport of lipophilic drug molecules in a new mucus-secreting cell culture model based on HT29-MTX cells. Pharm Res. 2001 Aug;18(8):1138–45.

    Article  CAS  PubMed  Google Scholar 

  94. 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 Jul;20(7):494–502.

    Article  CAS  PubMed  Google Scholar 

  95. Walter E, Janich S, Roessler BJ, Hilfinger JM, Amidon GL. HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: in vitro-in vivo correlation with permeability data from rats and humans. J Pharm Sci. 1996 Oct;85(10):1070–6.

    Article  CAS  PubMed  Google Scholar 

  96. Gebert A, Rothkötter HJ, Pabst R. M cells in Peyer’s patches of the intestine. Int Rev Cytol. 1996;167:91–159.

    Article  CAS  PubMed  Google Scholar 

  97. Schimpel C, Teubl B, Absenger M, Meindl C, Fröhlich E, Leitinger G, et al. Development of an advanced intestinal in vitro triple culture permeability model to study transport of nanoparticles. Mol Pharm. 2014 Mar 3;11(3):808–18.

    Article  CAS  PubMed  Google Scholar 

  98. Fan T, Chen C, Guo H, Xu J, Zhang J, Zhu X, et al. Design and evaluation of solid lipid nanoparticles modified with peptide ligand for oral delivery of protein drugs. Eur J Pharm Biopharm Off J Arbeitsgemeinschaft Pharm Verfahrenstechnik EV. 2014 Oct;88(2):518–28.

    Article  CAS  Google Scholar 

  99. Gamboa JM, Leong KW. In vitro and in vivo models for the study of oral delivery of nanoparticles. Adv Drug Deliv Rev. 2013 Jun 15;65(6):800–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Jin Y, Song Y, Zhu X, Zhou D, Chen C, Zhang Z, et al. Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport. Biomaterials. 2012 Feb;33(5):1573–82.

    Article  CAS  PubMed  Google Scholar 

  101. Li X, Guo S, Zhu C, Zhu Q, Gan Y, Rantanen J, et al. Intestinal mucosa permeability following oral insulin delivery using core shell corona nanolipoparticles. Biomaterials. 2013 Dec;34(37):9678–87.

    Article  CAS  PubMed  Google Scholar 

  102. Chen D, Xia D, Li X, Zhu Q, Yu H, Zhu C, et al. Comparative study of Pluronic(®) F127-modified liposomes and chitosan-modified liposomes for mucus penetration and oral absorption of cyclosporine a in rats. Int J Pharm. 2013 Jun 5;449(1–2):1–9.

    Article  CAS  PubMed  Google Scholar 

  103. Lamprecht A, Schäfer U, Lehr CM. Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa. Pharm Res. 2001 Jun;18(6):788–93.

    Article  CAS  PubMed  Google Scholar 

  104. Arbós P, Campanero MA, Arangoa MA, Renedo MJ, Irache JM. Influence of the surface characteristics of PVM/MA nanoparticles on their bioadhesive properties. J Control Release. 2003 Apr 14;89(1):19–30.

    Article  CAS  PubMed  Google Scholar 

  105. Gamboa JM, Leong KW. In vitro and in vivo models for the study of oral delivery of nanoparticles. Adv Drug Deliv Rev. 2013 Jun 15;65(6):800–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Sustr D, Hlaváček A, Duschl C, Volodkin D. Multi-fractional analysis of molecular diffusion in polymer multilayers by FRAP: a new simulation-based approach. J Phys Chem B. 2018 Jan 25;122(3):1323–33.

    Article  CAS  PubMed  Google Scholar 

  107. Lock JY, Carlson TL, Carrier RL. Mucus models to evaluate the diffusion of drugs and particles. Adv Drug Deliv Rev. 2018 Jan 15;124:34–49.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vivek Gupta .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 American Association of Pharmaceutical Scientists

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Parvathaneni, V., Kulkarni, N.S., Gupta, V. (2020). Current Status and Perspectives in Mucosal Drug Delivery of Nanotherapeutic Systems. In: Muttil, P., Kunda, N. (eds) Mucosal Delivery of Drugs and Biologics in Nanoparticles. AAPS Advances in the Pharmaceutical Sciences Series, vol 41. Springer, Cham. https://doi.org/10.1007/978-3-030-35910-2_4

Download citation

Publish with us

Policies and ethics