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Mucoadhesive Polymers as Enabling Excipients for Oral Mucosal Drug Delivery

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Oral Mucosal Drug Delivery and Therapy

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

The oral cavity, in particular the buccal mucosa, can be profitably employed for the administration of drugs intended for either local or systemic action. Conventional dosage forms are not able to assure therapeutic drug levels in the oral mucosa and in the systemic circulation; to obtain therapeutic action, it is required to develop oral mucoadhesive dosage forms, capable of withstanding the physiological removal action due to saliva and mechanical stresses and to prolong and improve the contact between the active substance and the mucosa. To achieve this aim, formulations intended for oral mucosal administration should contain mucoadhesive polymers as enabling excipients.

Several classes of polymers have been shown to possess pronounced adhesion properties when placed in contact with the oral mucosa. Their hydrophilic properties together with the capability to spread over the mucosal surface represent the main requirements to develop an intimate and prolonged contact with the mucosa. Good swelling properties are also important to favour the interpenetration between polymer and mucin chains. Furthermore, the ionic (cationic and anionic) charge density contributes to the formation of weak chemical bonds. Following the application of a dry or partially hydrated polymer, its hydration and the consequent mucus dehydration cause an increase in mucus cohesive properties which, in turn, promotes mucoadhesion. In summary, hydration, swelling and cohesive as well as rheological properties of the polymers are closely linked to their mucoadhesive properties.

This chapter focuses on the assessment of the mucoadhesive properties of materials, and the selection thereof, as based on a number of tests capable of evaluating the interplay of the above mechanisms depending also on the type of formulation/dosage form. Among mucoadhesive polymers, particular attention is paid to chitosans and hyaluronans, which are also endowed with absorption enhancement properties through the oral mucosa.

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References

  1. Bernkop-Schnurch A (2005a) Mucoadhesive systems in oral drug delivery. Drug Discov Today Technol 1:83–87

    Google Scholar 

  2. Chickering DE III, Mathiowitz E (1999) Definitions, mechanisms and theories of bioadhesion, cap 1. In: Mathiowitz E, Chickering DE III, Lehr C-M (eds) Bioadhesive drug delivery systems. Fundamental, novel approaches and development. Drug and pharmaceutical science, vol 98. Marcel Dekker Inc., New York, pp 1–10

    Google Scholar 

  3. Smart JD, Kellaway IW, Worthington HEC (1984) An in-vitro investigation of mucosa-adhesive materials for use in controlled drug delivery. J Pharm Pharmacol 36(5):295–299

    CAS  PubMed  Google Scholar 

  4. Smart JD (1999) The role of water movement and polymer hydration in mucoadhesion, cap.2. In: Mathiowitz E, Chickering DE III, Lehr C-M (eds) Bioadhesive drug delivery systems. Fundamental, novel approaches and development. Drug and pharmaceutical science, vol 98. Marcel Dekker Inc., New York, pp 11–23

    Google Scholar 

  5. Lee JW, Park JH, Robinson JR (2000) Bioadhesive-based dosage forms: the next generation. J Pharm Sci 89:850–866

    CAS  PubMed  Google Scholar 

  6. Smart JD (2005) The basic and the underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev 57:1556–1568

    CAS  PubMed  Google Scholar 

  7. Campbell BJ (1999) Biochemical and functional aspects of mucus and mucin-type glycoproteins, cap.5. In: Mathiowitz E, Chickering DE III, Lehr C-M (eds) Bioadhesive drug delivery systems. Fundamental, novel approaches and development, Drug and pharmaceutical science, vol 98. Marcel Dekker Inc., New York, pp 85–130

    Google Scholar 

  8. Peppas NA, Huang Y (2004) Nanoscale technologies of mucoadhesive interactions. Adv Drug Deliv Rev 56:1675–1687

    CAS  PubMed  Google Scholar 

  9. Edsman K, Hägerström H (2005) Pharmaceutical applications of mucoadhesion for the non-oral routes. J Pharm Pharmacol 57:3–22

    CAS  PubMed  Google Scholar 

  10. Khurana S, Madhav NVS (2011) Mucoadhesive drug delivery: mechanism and methods of evaluation. Int J Pharm Biosci 2(1):458–467

    Google Scholar 

  11. Derjaguin BV, Toporov YP, Muller VM, Aleinikova IN (1977) On the relationship between the molecular component of the adhesion of elastic particles to a solid surface. J Colloid Interface Sci 58:528–533

    Google Scholar 

  12. Good RJ (1977) Surface energy of solid and liquids: thermodynamics, molecular forces and structure. J Colloid Interface Sci 59:398–419

    CAS  Google Scholar 

  13. Tabor D (1977) Surface forces and interactions. J Colloid Interface Sci 58:2–13

    CAS  Google Scholar 

  14. Mikos AG, Peppas NA (1986) Systems for controlled release of drugs. V. Bioadhesive systems. STP Pharmacol 2:705–716

    Google Scholar 

  15. Baszikin A, Proust JE, Montesenego P, Boissonnade MM (1990) Wettability of polymers by mucin aqueous solutions. Biorheology 27:503–514

    Google Scholar 

  16. Ponchel G, Touchard F, Duchene D, Peppas N (1987) Bioadhesive analysis of controlled release systems. I. Fracture and interpenetration analysis in poly (acrylic acid) containing systems. J Control Release 5:129–141

    CAS  Google Scholar 

  17. Accili D, Manghi G, Bonacucina G, Di Martino P, Palmieri GF (2004) Mucoadhesion dependance of pharmaceutical polymers on mucosa characteristics. Eur J Pharm Sci 22:225–234

    CAS  PubMed  Google Scholar 

  18. Caramella CM, Rossi S, Bonferoni MC (1999) A rheological approach to explain the mucoadhesive behaviour of polymer hydrogel, cap.3. In: Mathiowitz E, Chickering DE III, Lehr C-M (eds) Bioadhesive drug delivery systems. Fundamental, novel approaches and development. Drug and pharmaceutical science, vol 98. Marcel Dekker Inc., New York, pp 25–65

    Google Scholar 

  19. Duchene D, Touchard F, Peppas NA (1988) Pharmaceutical and medical aspects of bioadhesive systems for drug administration. Drug Dev Ind Pharm 14:283–318

    CAS  Google Scholar 

  20. Bernkop-Schnurch A, Scholler S, Biebel RG (2000a) Development of controlled drug release systems based on polymer–cysteine conjugates. J Control Release 66:39–48

    CAS  PubMed  Google Scholar 

  21. Salamat-Miller N, Chittchang M, Johnston TP (2005) The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev 57:1666–1691

    CAS  PubMed  Google Scholar 

  22. Hearnden V, Sankar V, Hull K, Vidović Juras D, Greenberg M, Kerr AR, Lockhart PB, Patton LL, Porter S, Thornhill MH (2012) New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Adv Drug Deliv Rev 64:16–28

    CAS  PubMed  Google Scholar 

  23. Rossi S, Sandri G, Caramella C (2005a) Buccal drug delivery: a challenge already won? Drug Discov Today Technol 2(1):59–65

    CAS  PubMed  Google Scholar 

  24. Chinna Reddy P, Chaitanya KSC, Madhusudan Rao Y (2011) A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. Daru 19(6):385–403

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Alur HH (2001) Peptides and proteins: buccal absorption. In: Swarbrick J, Boylan JC (eds) Encyclopedia of pharmaceutical technology, vol 20(3). Marcel Dekker Inc., New York, pp 193–218

    Google Scholar 

  26. Lueßen HL (1996) Mucoadhesive polymers in peroral peptide drug delivery. Influence of mucoadhesive excipients on the proteolytic activity of intestinal enzymes. Eur J Pharm Sci 4:117–128

    Google Scholar 

  27. Bernkop-Schnurch A (1997) Novel bioadhesive chitosan-EDTA conjugate protects leucine enkephalin from degradation by aminopeptidase N. Pharm Res 14:917–922

    CAS  PubMed  Google Scholar 

  28. Bernkop-Schnurch A, Krauland AH, Leitner VM, Palmberger T (2004) Thiomers: potential excipients for non-invasive peptide delivery systems. Eur J Pharm Biopharm 58:253–263

    CAS  PubMed  Google Scholar 

  29. Palem CR, Battu SK, Ganu R, Yamsani VV, Repka MA, Yamsani MR (2012) Role of cyclodextrin complexation in felodipine-sustained release matrix tablets intended for oral transmucosal delivery: in vitro and ex vivo characterization. Pharm Dev Tech 17(3):321–332

    CAS  Google Scholar 

  30. Jacobsen J, Bjerregaard S, Pedersen M (1999) Cyclodextrin inclusion complexes of anti mycotics intended to act in the oral cavity-drug supersaturation, toxicity on TR 146 cells and release from a delivery system. Eur J Pharm Biopharm 48(3):217–224

    CAS  PubMed  Google Scholar 

  31. Patel VF, Liu F, Brown MB (2011) Advances in oral transmucosal drug delivery. J Control Release 153:106–116

    CAS  PubMed  Google Scholar 

  32. Madhav NVS, Semwal R, Semwal DK, Semwal RB (2012) Recent trends in oral transmucosal drug delivery systems: an emphasis on the soft palatal route. Expert Opin Drug Deliv 9(6):629–647

    Google Scholar 

  33. Khanvilkar K, Donovanl MD, Flanagan DR (2001) Drug transfer through mucus. Adv Drug Deliv Rev 48(2–3):173–193

    CAS  PubMed  Google Scholar 

  34. Roberts GAF (1992) Chitin chemistry. Mac Millan, London, pp 1–110, 274–315

    Google Scholar 

  35. Tsaih M, Chen R (1999) Effects of ionic strength and pH on the diffusion coefficients and conformation of chitosans in molecule solution. J Appl Polym Sci 73:2041–2050

    CAS  Google Scholar 

  36. Şenel S, Ikinci G, Kas S, Yousefi-Rad A, Sargon MF, Hincal AA (2000) Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm 193:197–203

    PubMed  Google Scholar 

  37. Chen JL, Cyr GN (1970) Compositions producing adhesion through hydration. In: Manly RS (ed) Adhesion in biological systems. Academic, New York, pp 163–181

    Google Scholar 

  38. Lehr CM, Bouwstra JA, Schacht EH, Junginger HE (1992) In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm 78:43–48

    CAS  Google Scholar 

  39. Fiebrig I, Harding SE, Rowe AJ, Hyman SC, Davis SS (1995) Transmission electron microscopy on pig gastric mucin and its interactions with chitosan. Carbohydr Polym 28:239–244

    CAS  Google Scholar 

  40. He P, Davis SS, Illum L (1998) In vitro evaluation of the mucoadhesive properties of chitosan microspheres. Int J Pharm 166:75–88

    CAS  Google Scholar 

  41. Deacon MP, McGurk S, Roberts CJ, Williams PM, Tendler SJB, Davies MC, Davies SS, Harding SE (2000) Atomic force microscopy of gastric mucin and chitosan mucoadhesive systems. Biochem J 348:557–563

    PubMed Central  CAS  PubMed  Google Scholar 

  42. Patel D, Smith AW, Grist N, Barnett P, Smart JD (1999) An in vitro mucosal model predictive of bioadhesive agents onto the oral cavity. J Control Release 61:175–183

    CAS  PubMed  Google Scholar 

  43. Nordman H, Davies JR, Herrman A, Karlsson NG, Hanson GC, Carlstedt I (1997) Mucus glycoproteins from pig gastric mucosa: identification of different mucin populations from the surface epithelium. Biochem J 326:903–910

    PubMed Central  CAS  PubMed  Google Scholar 

  44. Lehr CM, Bouwstra JA, Schacht EH, Junginger HE (1992) In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm 78:43–48

    CAS  Google Scholar 

  45. Peppas NA, Buri PA (1985) Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues. J Control Release 2:257–275

    CAS  Google Scholar 

  46. Rossi S, Ferrari F, Bonferoni MC, Caramella C (2001) Characterization of chitosan hydrochloride-mucin rheological interaction: influence of polymer concentration and polymer: mucin weight ratio. Eur J Pharm Sci 12(4):479–485

    CAS  PubMed  Google Scholar 

  47. Bernkop-Schnurch A, Humenberger C, Valenta C (1998) Basic studies on bioadhesive delivery systems for peptide and protein drugs. Int J Pharm 165:217–225

    CAS  Google Scholar 

  48. Genta I, Perugini P, Pavanetto F, Modena T, Conti B, Muzzarelli RA (1999) Microparticulate drug delivery systems. EXS 87:305–313

    CAS  PubMed  Google Scholar 

  49. Gåserød O, Jolliffe AG, Hampson FC, Dettmar PW, Skjåk-Bræk G (1998) The enhancement of the bioadhesive properties of calcium alginate gel beads by coating with chitosan. Int J Pharm 175:237–246

    Google Scholar 

  50. Takeuchi H, Yamamoto H, Niwa T, Hino T, Kawashima Y (1996) Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes. Pharm Res 13:896–901

    CAS  PubMed  Google Scholar 

  51. Yamamoto H, Takeuchi H, Hino T, Kawashima Y (2000) Mucoadhesive liposomes: physicochemical properties and release behaviour of water-soluble drugs from chitosan coated liposomes. STP Pharm Sci 10:63–68

    CAS  Google Scholar 

  52. Remuñan-López C, Portero A, Lemos M, Vila-Jato JL, Nuñez MJ, Riveiro P, López JM, Piso M, Alonso MJ (2000) Chitosan microspheres for the specific delivery of amoxycillin to the gastric cavity. STP Pharm Sci 10:69–76

    Google Scholar 

  53. Shimoda J, Onishi H, Machida Y (2001) Bioadhesive characteristics of chitosan microspheres to the mucosa of rat small intestine. Drug Dev Ind Pharm 27:567–576

    CAS  PubMed  Google Scholar 

  54. Jiménez-Castellanos NR, Zia H, Rhodes CT (1993) Mucoadhesive drug delivery systems. Drug Dev Ind Pharm 19:143–194

    Google Scholar 

  55. Felt O, Buri P, Gurny R (1998) Chitosan: a unique polysaccharide for drug delivery. Drug Dev Ind Pharm 24:979–993

    CAS  PubMed  Google Scholar 

  56. Artursson P, Lindmark T, Davis SS, Illum L (1994) Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2). Pharm Res 11:1358–1361

    CAS  PubMed  Google Scholar 

  57. Dodane V, Amin Khan A, Mervin JR (1999) Effect of chitosan on epithelial permeability and structure. Int J Pharm 182:21–32

    CAS  PubMed  Google Scholar 

  58. Thanou MM, Kotzé AF, Scharringhausen T, Lueï¢en HL, de Boer AG, Verhoef JC, Junginger HE (2000) Effect of degree of quaternization of N-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal Caco-2 cell monolayers. J Control Release 64:15–25

    CAS  PubMed  Google Scholar 

  59. Hamman JH, Stander M, Kotzè AF (2002) Effect of the degree of quaternization of N-trimethyl chitosan chloride on absorption enhancement: in vivo evaluation in rat nasal epithelia. Int J Pharm 232:235–242

    CAS  PubMed  Google Scholar 

  60. Hamman JH, Schultz CM, Kotzè AF (2003) N-trimethyl chitosan chloride: optimum degree of quaternization for drug absorption enhancement across epithelial cells. Drug Dev Ind Pharm 29:161–172

    CAS  PubMed  Google Scholar 

  61. Rossi S, Sandri G, Ferrari F, Bonferoni MC, Caramella C (2003a) Buccal delivery of acyclovir from films based on chitosan and polyacrylic acid. Pharm Dev Technol 8(2):199–208

    CAS  PubMed  Google Scholar 

  62. Sandri G, Rossi S, Ferrari F, Bonferoni MC, Muzzarelli C, Caramella C (2004a) Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur J Pharm Sci 21:351–359

    CAS  PubMed  Google Scholar 

  63. Sandri G, Rossi S, Bonferoni MC, Ferrari F, Zambito Y, Di Colo G, Caramella C (2005) Buccal penetration enhancement properties of N-trimethyl chitosan: influence of quaternization degree on absorption of a high molecular weight molecule. Int J Pharm 297:146–155

    CAS  PubMed  Google Scholar 

  64. Rossi S, Sandri G, Ferrari F, Bonferoni MC, Caramella C (2003b) Development of films and matrices based on chitosan and polyacrylic acid for vaginal delivery of acyclovir. STP Pharm Sci 13:181–189

    Google Scholar 

  65. Yi X, Wang Y, Yu FS (2000) Corneal epithelial tight junctions and their response to lipopolysaccharide challenge. Invest Ophthalmol Vis Sci 41:4093–4100

    CAS  PubMed  Google Scholar 

  66. Di Colo G, Burgalassi S, Zambito Y, Monti D, Chetoni P (2004) Effects of different N-trimethyl chitosans on in vitro/in vivo ofloxacin transcorneal permeation. J Pharm Sci 93:2851–2862

    CAS  PubMed  Google Scholar 

  67. Reichl S, Muller-Goymann CC (2003) The use of a porcine organotypic cornea construct for permeation studies from formulations containing befunolol hydrochloride. Int J Pharm 250:191–201

    CAS  PubMed  Google Scholar 

  68. Li Q, Dunn ET, Grandmaison EW, Goosen MFA (1992) Applications and properties of chitosan. J Bioact Compat Polym 7:370–397

    CAS  Google Scholar 

  69. Illum L (1998) Chitosan and its use as a pharmaceutical excipient. Pharm Res 15:1326–1331

    CAS  PubMed  Google Scholar 

  70. Dodane V, Vilivalam VD (1998) Pharmaceutical applications of chitosano. Pharm Sci Technol Today 1:246–253

    CAS  Google Scholar 

  71. Paul W, Sharma CP (2000) Chitosan, a drug carrier for 21st century: a review. STP Pharm Sci 10:5–22

    CAS  Google Scholar 

  72. Janes KA, Calvo P, Alonso MJ (2001) Polysaccharide colloidal particles as delivery systems for macromolecules. Adv Drug Deliv Rev 47:83–97

    CAS  PubMed  Google Scholar 

  73. Singla AK, Chawla M (2001) Chitosan: some pharmaceutical and biological aspects—an update. J Pharm Pharmacol 53:1047–1067

    CAS  PubMed  Google Scholar 

  74. Alonso MJ, Sanchez A (2003) The potential of chitosan in ocular drug delivery. J Pharm Pharmacol 55(11):1451–1463

    CAS  PubMed  Google Scholar 

  75. Arai K, Kinumaki T, Fujita T (1968) Toxicity of chitosan. Bull Tokai Reg Fish Res Lab 43:89–94

    Google Scholar 

  76. Muzzarelli R, Baldassare V, Conti F, Ferrara P, Biagini G, Gazzanelli G, Vasi V (1988) Biological activity of chitosan: ultrastructure study. Biomaterials 9:247–252

    CAS  PubMed  Google Scholar 

  77. Knapczyk J, Krówczynski L, Pawlik B, Liber Z (1989) Pharmaceutical dosage forms with chitosan. In: Skjåk-Bræek G, Anthonsen T, Sandford P (eds) Chitin and chitosan: sources, chemistry, biochemistry, physical properties and applications. Elsevier, London, pp 665–670

    Google Scholar 

  78. Kim S-K, Park P-J, Yang H-P, Han S-S (2001) Subacute toxicity of chitosan oligosaccharide in Sprague-Dawley rats. Arzneimittelforschung 51:769–774

    CAS  PubMed  Google Scholar 

  79. Knapczyk J (1993) Chitosan hydrogel as a base for semisolid drug forms. Int J Pharm 93:233–237

    CAS  Google Scholar 

  80. Kristl J, Smid-Korbar J, Struc E, Schara M, Rupprecht H (1993) Hydrocolloids and gels of chitosan as drug carriers. Int J Pharm 99:13–19

    CAS  Google Scholar 

  81. Kawashima Y, Lin SY, Kasai A, Handa T, Takenaka H (1985) Preparation of a prolonged release tablet of aspirin with chitosan. Chem Pharm Bull 33:2107–2113

    CAS  PubMed  Google Scholar 

  82. Acartürk F (1989) Preparation of a prolonged-release tablet formulation of diclofenac sodium. Pharmazie 44:547–549

    PubMed  Google Scholar 

  83. Hou W-M, Miyazaki S, Takada M, Komai T (1985) Sustained release of indomethacin from chitosan granules. Chem Pharm Bull 33:3986–3992

    CAS  PubMed  Google Scholar 

  84. Goskonda S, Upadrashta S (1993) Avicel RC591/chitosan beads by extrusion-spheronization technology. Drug Dev Ind Pharm 19:915–927

    CAS  Google Scholar 

  85. Thanoo C, Sunny MC, Jayakrishnan A (1992) Cross-linked chitosan microspheres: preparation and evaluation as a matrix for the controlled release of pharmaceuticals. J Pharm Pharmacol 44:283–286

    CAS  PubMed  Google Scholar 

  86. Chandy T, Sharma CP (1993) Chitosan matrix for oral sustained delivery of ampicillin. Biomaterials 14:939–944

    CAS  PubMed  Google Scholar 

  87. Kas S (1997) Chitosan: properties, preparations and application to microparticulate systems. J Microencapsul 14:689–711

    CAS  PubMed  Google Scholar 

  88. Sawayanagi Y, Nambu N, Nagai T (1982a) Directly compressed tablets containing chitin or chitosan in addition to lactose or potato starch. Chem Pharm Bull 30:2935–2940

    CAS  PubMed  Google Scholar 

  89. Sawayanagi Y, Nambu N, Nagai T (1982b) Directly compressed tablets containing chitin or chitosan in addition to mannitol. Chem Pharm Bull 30:4216–4218

    CAS  Google Scholar 

  90. Ritthidej G, Chomto P, Pummangura S, Menasveta P (1994) Chitin and chitosan as disintegrants in paracetamol tablets. Drug Dev Ind Pharm 20:2109–2134

    CAS  Google Scholar 

  91. Shiraishi S, Arahira M, Imai T, Otagri M (1990) Enhancement of dissolution rates of several drugs by low-molecular chitosan and alginate. Chem Pharm Bull 38:185–187

    CAS  Google Scholar 

  92. Portero A, Remuñan-López C, Vila-Jato JL (1998) Effect of chitosan and chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine. Int J Pharm 175:75–84

    CAS  Google Scholar 

  93. Rossi S, Sandri G, Caramella C (2005b) Buccal delivery systems for peptides: recent advances. Am J Drug Deliv 3(4):215–225

    CAS  Google Scholar 

  94. Ikinci G, Şenel S, Akincibay H, Kas S, Ercis S, Wilson CG, Hincal AA (2002) Effect of chitosan on a periodontal pathogen porphyromonas gingivalis. Int J Pharm 235:121–127

    CAS  PubMed  Google Scholar 

  95. Snyman D, Hamman JH, Kotzè AF (2003) Evaluation of mucoadhesive properties of N-trimethyl chitosan chloride. Drug Dev Ind Pharm 29:61–69

    CAS  PubMed  Google Scholar 

  96. Illum L, Farraj NF, Davis SS (1994) Chitosan as a novel nasal delivery system for peptide drugs. Pharm Res 11:1186–1189

    CAS  PubMed  Google Scholar 

  97. Thanou MM, Verhoef JC, Junginger HE (2001) Oral drug absorption enhancement by chitosan and its derivatives. Adv Drug Deliv Rev 52:117–126

    CAS  PubMed  Google Scholar 

  98. Junginger HE, Verhoef JC (1998) Macromolecules as safe penetration enhancers for hydrophilic drugs—a fiction? Pharm Sci Technol Today 1:370–376

    CAS  Google Scholar 

  99. Goa KL, Benfield P (1994) Hyaluronic acid, a review of its pharmacology and use as surgical aid in ophthalmology, and its therapeutic potential in joint disease and wound healing. Drugs 47:536–566

    CAS  PubMed  Google Scholar 

  100. Pritchard K, Lansley AB, Martin GP, Heliwell M, Mariott C, Benedetti LM (1996) Evaluation of the bioadhesive properties of hyaluronan derivatives: detachment weight and mucociliary transport rate studies. Int J Pharm 129:137–145

    CAS  Google Scholar 

  101. Sandri G, Rossi S, Ferrari F, Bonferoni MC, Zerrouk N, Caramella C (2004b) 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 56(9):1083–1090

    CAS  PubMed  Google Scholar 

  102. Bonucci E, Ballanti P, Ramires PA, Richardson JL, Benedetti LM (1995) Prevention of ovariectomy osteopenia in rats after vaginal administration of Hyaff 11 microspheres containing salmon calcitonin. Calcif Tissue Int 56(4):274–279

    CAS  PubMed  Google Scholar 

  103. Puccio A, Ferrari F, Rossi S, Bonferoni MC, Sandri G, Dacarro C, Grisoli P, Caramella C (2011) Comparison of functional and biological properties of chitosan and hyaluronic acid, to be used for the treatment of mucositis in cancer patients. J Drug Deliv Sci Tech 21(3):241–247

    CAS  Google Scholar 

  104. Sukumar S, Dřízhal I (2007) Hyaluronic acid and periodontitis. Acta Medica 50(4):225–228

    CAS  PubMed  Google Scholar 

  105. Rajan P, Nair D, Kumar CS, Dusanapudi LN (2013) Hyaluronic acid—a simple, unusual polysaccharide: a potential mediator for periodontal regeneration. Univ Res J Dent 3(3):113–119

    Google Scholar 

  106. Kumar V, Banker GS (1993) Chemically-modified cellulosic polymers. Drug Dev Ind Pharm 19(1–2):1–31

    CAS  Google Scholar 

  107. Valenta C (2005) The use of mucoadhesive polymers in vaginal delivery. Adv Drug Deliv Rev 57:1692–1712

    CAS  PubMed  Google Scholar 

  108. Ludwig A (2005) The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev 57:1595–1639

    CAS  PubMed  Google Scholar 

  109. Grabovac V, Gucci D, Bernkop-Schnurch A (2005) Comparison of the mucoadhesive properties of various polymers. Adv Drug Deliv Rev 57:1713–1723

    CAS  PubMed  Google Scholar 

  110. Ferrari F, Bertoni M, Caramella C, La Manna A (1994) Description and validation of an apparatus for gel strength measurements. Int J Pharm 109:115–124

    CAS  Google Scholar 

  111. Rossi S, Bonferoni MC, Lippoli G, Bertoni M, Ferrari F, Caramella C, Conte U (1995) Influence of mucin type on polymer-mucin rheological interactions. Biomaterials 16:1073–1079

    CAS  PubMed  Google Scholar 

  112. Madsen F, Eberth K, Smart JD (1998) A rheological assessment of the nature of interactions between mucoadhesive polymers and a homogenised mucus gel. Biomaterials 19:1083–1092

    CAS  PubMed  Google Scholar 

  113. Rillosi M, Buckton G (1995) Modelling mucoadhesion by use of surface energy terms obtained from the Lewis acid-Lewis base approach. II. Studies on anionic, cationic, and unionisable polymers. Pharm Res 12(5):669–675

    CAS  PubMed  Google Scholar 

  114. Bhimrao JK, Kishanchandra KR, Anant KR, Sambhaji PS (2004) Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases. Drug Dev Ind Pharm 30(2):195–203

    Google Scholar 

  115. Repka MA, ElSohly MA, Munjal M, Ross SA (2006) Temperature stability and bioadhesive properties of Δ9-tetrahydrocannabinol incorporated hydroxypropylcellulose polymer matrix systems. Drug Dev Ind Pharm 32(1):21–32

    PubMed Central  CAS  PubMed  Google Scholar 

  116. Singla AK, Chawla M, Singh A (2000) Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: a review. Drug Dev Ind Pharm 26(9):913–924

    CAS  PubMed  Google Scholar 

  117. Mortazavi SA (1995) An in-vitro assessment of mucus/mucoadhesive interactions. Int J Pharm 124:173–182

    CAS  Google Scholar 

  118. Warren SJ, Kellaway W (1998) The synthesis and in vitro characterization of the mucoadhesion and swelling of poly(acrylic acid) hydrogels. Pharm Dev Technol 3(2):199–208

    Google Scholar 

  119. Park H, Robinson JR (1987) Mechanisms of mucoadhesion of poly(acrylic acid) hydrogels. Pharm Res 4(6):457–464

    CAS  PubMed  Google Scholar 

  120. Dubolazov AV, Nurkeeva ZS, Mun GA, Khutoryanskiy VV (2006) Design of mucoadhesive polymeric films based on blends of poly (acrylic acid) and (hydroxypropyl) cellulose. Biomacromolecules 7(5):1637–1643

    CAS  PubMed  Google Scholar 

  121. Tobyn M, Johnson JR, Dettmar PW (1996) Factors affecting in vitro gastric mucoadhesion. Part2. Physical properties of polymers. Eur J Pharm Biopharm 42(1):56–61

    CAS  Google Scholar 

  122. Mortazavi SA, Smart JD (1993) An investigation into the role of water movement and mucus gel dehydration in mucoadhesion. J Control Release 25:197–203

    CAS  Google Scholar 

  123. Shojaei AH, Zhuo SL, Li X (1998) Transbuccal delivery of acyclovir (II): feasibility, system design, and in vitro permeation studies. J Pharm Sci 1(2):66–73

    CAS  Google Scholar 

  124. Serra L, Domenich J, Peppas NA (2006) Design of poly(ethylene glycol)-tethered copolymers as novel mucoadhesive drug delivery systems. Eur J Pharm Biopharm 63(1):11–18

    CAS  PubMed  Google Scholar 

  125. Shojaei AH, Paulson J, Honary S (2000) Evaluation of poly(acrylic acid-co-ethylhexyl acrylate films for mucoadhesive transbuccal drug delivery: factors affecting the force of mucoadhesion. J Control Release 67(2–3):223–232

    CAS  PubMed  Google Scholar 

  126. Xiang J, Li X (2004) Novel mucoadhesive polymer: synthesis and mucoadhesion of poly [acrylic acid-co-poly (ethylene glycol) monomethylether monomethacrylate-co-dimethylaminoethyl methacrylate. J Appl Polym Sci 94(6):2431–2437

    CAS  Google Scholar 

  127. Andrews GP, Laverty TP, Jones DS (2009) Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm 71:505–518

    CAS  PubMed  Google Scholar 

  128. Leitner VM, Walker GF, Bernkop-Schnurch A (2003) Thiolated polymers: evidence for the formation of disulphide bonds with mucus glycoproteins. Eur J Pharm Biopharm 56:207–214

    CAS  PubMed  Google Scholar 

  129. Bernkop-Schnurch A, Hornhof M, Zoldi T (2003) Thiolated polymers—thiomers: modification of chitosan with 2-iminothiolane. Int J Pharm 260:229–237

    CAS  PubMed  Google Scholar 

  130. Marschutz MK, Bernkop-Schnurch A (2002a) Thiolated polymers: advance in mucoadhesion by use of in-situ cross linking cysteine conjugates. Eur J Pharm Sci 15:387–394

    CAS  PubMed  Google Scholar 

  131. Bernkop-Schnurch A (2005b) Thiomers: a new generation of mucoadhesive polymers. Adv Drug Deliv Rev 57:1569–1582

    PubMed  Google Scholar 

  132. Bernkop-Schnurch A, Schwarz V, Steininger S (1999) Polymers with thiol groups: a new generation of mucoadhesive polymers? Pharm Res 16:876–881

    CAS  PubMed  Google Scholar 

  133. Marschutz MK, Bernkop-Schnurch A (2002b) Thiolated polymers: selfcrosslinking properties of thiolated 450 kDa polyacrylic acid and their influence on mucoadhesion. Eur J Pharm Sci 15:387–394

    CAS  PubMed  Google Scholar 

  134. Bernkop-Schnurch A, Steininger S (2000b) Synthesis and characterisation of mucoadhesive thiolated polymers. Int J Pharm 194:239–247

    CAS  PubMed  Google Scholar 

  135. Bernkop-Schnurch A, Kast CE, Richter MF (2001) Improvement in the mucoadhesive properties of alginate by the covalent attachment of cysteine. J Control Release 71:277–285

    CAS  PubMed  Google Scholar 

  136. Langoth N, Kalbe J, Bernkp-Schnurch A (2003) Development of buccal drug delivery systems based on a thiolated polymer. Int J Pharm 252:141–148

    CAS  PubMed  Google Scholar 

  137. Marschutz MK, Caliceti P, Bernkop-Schnurch A (2000) Design and in vivo evaluation of an oral delivery system for insulin. Pharm Res 17:1468–1474

    CAS  PubMed  Google Scholar 

  138. Kast CE, Guggi D, Langoth N, Bernkop-Schnürch A (2003) Development and in vivo evaluation of an oral delivery system for low molecular weight heparin based on thiolated polycarbophil. Pharm Res 20:931–936

    CAS  PubMed  Google Scholar 

  139. Leitner V, Guggi D, Bernkop-Schnürch A (2004) Thiomers in non-invasive peptide delivery: in vitro and in vivo characterisation of a polycarbophil–cysteine/glutathione gel formulation for hGH. J Pharm Sci 93:1682–1691

    CAS  PubMed  Google Scholar 

  140. Weidener J (2003) Mucoadhesive ocular inserts as an improved delivery vehicle for ophthalmic indications. Drug Discov Today 8:906–907

    Google Scholar 

  141. Hornof M, Weyenberg W, Ludwig A, Bernkop-Schnrch A (2003) Mucoadhesive ocular insert based on thiolated poly(acrylic acid): development and in vivo evaluation in humans. J Control Release 89:419–428

    CAS  PubMed  Google Scholar 

  142. Clark MA, Hirst B, Jepson M (2000) Lectin-mediated mucosal delivery of drugs and microparticles. Adv Drug Deliv Rev 43:207–223

    CAS  PubMed  Google Scholar 

  143. Hassan EE, Gallo JM (1990) A simple rheological emthod for the in vitro assessment of mucin-polymer bioadhesive bond strength. Pharm Res 7:491–495

    CAS  PubMed  Google Scholar 

  144. Caramella C, Bonferoni MC, Rossi S, Ferrari F (1994) Rheological and tensile tests for the assessment of polymer-mucin interactions. Eur J Pharm Biopharm 40(4):213–217

    CAS  Google Scholar 

  145. Sandri G, Rossi S, Bonferoni MC, Ferrari F, Mori M, Caramella C (2012) The role of chitosan as a mucoadhesive agent in mucosal drug delivery. J Drug Deliv Sci Tech 22(4):275–284

    CAS  Google Scholar 

  146. Hägerström H, Bergström CAS, Edsman K (2004) The importance of gel properties for mucoadhesion measurements: a multivariate analysis approach. J Pharm Pharmacol 56:161–168

    PubMed  Google Scholar 

  147. Sandri G, Bonferoni MC, Ferrari F, Rossi S, Del Fante C, Perotti C, Gallanti A, Caramella C (2011) An in situ gelling buccal spray containing platelet lysate for the treatment of oral mucositis. Curr Drug Discov Technol 8(3):277–285

    CAS  PubMed  Google Scholar 

  148. Bonferoni MC, Rossi S, Ferrari F, Caramella C (1999) A modified Franz diffusion cell for simultaneous assessment of drug release and washability of mucoadhesive gel. Pharm Dev Technol 4:45–54

    CAS  PubMed  Google Scholar 

  149. Rossi S, Bonferoni MC, Ferrari F, Caramella C (1999) Drug release and washability of mucoadhesive gels based on sodium carboxymethylcellulose and polyacrylic acid. Pharm Dev Technol 4:55–63

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Drug Sciences, University of Pavia, Via Taramelli, 12, 27100, Pavia, Italy

    Giuseppina Sandri, Silvia Rossi, Franca Ferrari, Maria Cristina Bonferoni & Prof. Carla M. Caramella

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  1. Giuseppina Sandri
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  2. Silvia Rossi
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  3. Franca Ferrari
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  4. Maria Cristina Bonferoni
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  5. Prof. Carla M. Caramella
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Correspondence to Carla M. Caramella .

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  1. Ulti Pharmaceuticals Ltd., Hamilton, New Zealand

    Michael J. Rathbone

  2. Hacettepe University, Faculty of Pharmacy, Ankara, Turkey

    Sevda Senel

  3. California Northstate University, College of Pharmacy, Elk Grove, California, USA

    Indiran Pather

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Sandri, G., Rossi, S., Ferrari, F., Bonferoni, M., Caramella, C. (2015). Mucoadhesive Polymers as Enabling Excipients for Oral Mucosal Drug Delivery. In: Rathbone, M., Senel, S., Pather, I. (eds) Oral Mucosal Drug Delivery and Therapy. Advances in Delivery Science and Technology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7558-4_4

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