Mucoadhesive polymers for oral transmucosal drug delivery: A review

Current Pharmaceutical Design

Volumn 18, Issue 34, 2012, Pages 5497-5514

  Bagan, Jose' ^a   Paderni, Carlo ^b   Termine, Nicoletta ^b   Campisi, Giuseppina ^b   Lo Russo, Lucio ^c   Compilato, Domenico ^b   Di Fede, Olga ^b  

^a UNIVERSITY OF VALENCIA   (Spain)

^b UNIVERSITY OF PALERMO   (Italy)

^c UNIVERSITY OF FOGGIA   (Italy)

Author keywords

Dosage form; Drug controlled release; Mucoadhesion; Mucoadhesive polymers; Mucosal permeability; Oral mucosa; Oral transmucosal drug delivery

Indexed keywords

MUCIN; POLYMER;

BASEMENT MEMBRANE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DOSAGE FORM; DRUG FORMULATION; DRUG PENETRATION; GINGIVA; HARD PALATE; HUMAN; LAMINA PROPRIA; MECHANICAL STRESS; MOUTH CAVITY; MOUTH MUCOSA; MUCOADHESION; MUCOSAL ADMINISTRATION; MUCUS; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REVIEW; SALIVA; SUBMUCOSA; SUSTAINED DRUG RELEASE; TABLET FORMULATION;

ADHESIVENESS; ANIMALS; BIOLOGICAL AVAILABILITY; DELAYED-ACTION PREPARATIONS; DRUG DELIVERY SYSTEMS; HUMANS; MOUTH MUCOSA; PHARMACEUTICAL PREPARATIONS; POLYMERS;

EID: 84867733509     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161212803307545     Document Type: Review

References (151)

1. Sayani AP, Chien YW. Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Ther Drug Carrier Syst 1996; 13: 85-184.
2. Song Y, Wang Y, Thakur R, Meidan VM, Michniak B. Mucosal drug delivery: membranes, methodologies, and applications. Crit Rev Ther Drug Carrier Syst 2004; 21: 195-256.
3. Lee VH. Mucosal drug delivery. J Natl Cancer Inst Monogr 2001: 41-4.
4. Harris D, Robinson JR. Drug delivery via the mucous membranes of the oral cavity. J Pharm Sci 1992; 81: 1-10.
5. Hao J, Heng PW. Buccal delivery systems. Drug Dev Ind Pharm 2003; 29: 821-32.
6. Veuillez F, Kalia YN, Jacques Y, Deshusses J, Buri P. Factors and strategies for improving buccal absorption of peptides. Eur J Pharm Biopharm 2001; 51: 93-109.
7. Birudaraj R, Mahalingam R, Li X, Jasti BR. Advances in buccal drug delivery. Crit Rev Ther Drug Carrier Syst 2005; 22: 295-330.
8. Khutoryanskiy VV. Advances in mucoadhesion and mucoadhesive polymers. Macromol Biosci 2011; 11: 748-64.
9. Smart JD. Buccal drug delivery. Expert Opin Drug Deliv 2005; 2: 507-17.
10. Harris D, Robinson JR. Bioadhesive polymers in peptide drug delivery. Biomaterials 1990; 11: 652-8.
11. Senel S, Hincal AA. Drug permeation enhancement via buccal route: possibilities and limitations. J Control Release 2001; 72: 133-44.
12. Salamat-Miller N, Chittchang M, Johnston TP. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev 2005; 57: 1666-91.
13. Chen SY, Squier CA. The ultrastructure of the oral epithelium. In Meyer J, Squier CA, Gerson SJ, Eds. The structure and function of oral mucosa. Pergamon Press: London 1984, pp. 7-30.
14. Gandhi RB, Robinson JR. Oral cavity as a site for bioadhesive drug delivery. Adv. Drug Deliv. rev. 1994; 13: 43-74.
15. Shojaei AH. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharm Sci 1998; 1: 15-30.
16. Squier CA, Johnson NW, Hopps RM, Eds. Human oral mucosa: development, structure and function. Oxford (UK): Blackwell Scientific 1976.
17. Collins LM, Dawes C. The surface area of the adult human mouth and thickness of the salivary film covering the teeth and oral mucosa. J Dent Res 1987; 66: 1300-2.
18. Rathbone MJ, Hadgraft J. Absorption of drugs from the human oral cavity. Int J Pharm 1991; 74: 9-24.
19. Squier CA, Johnson NW. Permeability of oral mucosa. Br Med Bull 1975; 31: 169-75.
20. Campisi G, Paderni C, Saccone R, Di Fede O, Wolff A, Giannola LI. Human buccal mucosa as an innovative site of drug delivery. Curr Pharm Des 2010; 16: 641-52.
21. Squier CA. The permeability of keratinized and nonkeratinized oral epithelium to horseradish peroxidase. J Ultrastruct Res 1973; 43: 160-77.
22. Squier CA, Wertz PW. Structure and function of the oral mucosa and implications for drug delivery. In Rathbone MJ, Ed. Oral Mucosal Drug Delivery. New York: Marcel Dekker 1996.
23. Wertz PW, Squier CA. Cellular and molecular basis of barrier function in oral epithelium. Crit Rev Ther Drug Carrier Syst 1991; 8: 237-69.
24. Wertz PW, Swartzendruber DC, Squier CA. Regional variation in the structure and permeability of oral mucosa and skin. Adv. Dug Deliv Rev 1993; 12: 1-12.
25. Squier CA, Kremer MJ. Biology of oral mucosa and esophagus. J Natl Cancer Inst Monogr 2001; (29): 7-15.
26. Galey WR, Lonsdale HK, Nacht S. The in vitro permeability of skin and buccal mucosa to selected drugs and tritiated water. J Invest Dermatol 1976; 67: 713-7.
27. Squier CA, Cox P, Wertz PW. Lipid content and water permeability of skin and oral mucosa. J Invest Dermatol 1991; 96: 123-6.
28. Squier CA, Wertz PW, Cox P. Thin-layer chromatographic analyses of lipids in different layers of porcine epidermis and oral epithelium. Arch Oral Biol 1991; 36: 647-53.
29. Sudhakar Y, Kuotsu K, Bandyopadhyay AK. Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs. J Control Release 2006; 114: 15-40.
30. Zhang H, Zhang J, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 2002; 41: 661-80.
31. Madison KC, Sando GN, Howard EJ, et al. Lamellar granule biogenesis: a role for ceramide glucosyltransferase, lysosomal enzyme transport, and the Golgi. J Investig Dermatol Symp Proc 1998; 3: 80-6.
32. Madison KC, Swartzendruber DC, Wertz PW, Downing DT. Presence of intact intercellular lipid lamellae in the upper layers of the stratum corneum. J Invest Dermatol 1987; 88: 714-8.
33. Matoltsy AG. Keratinization. J Invest Dermatol 1976; 67: 20-5.
34. Squier CA. Zinc iodide-osmium staining of membrane-coating granules in keratinized and non-keratinized mammalian oral epithelium. Arch Oral Biol 1982; 27: 377-82.
35. Lavker RM. Membrane coating granules: the fate of the discharged lamellae. J Ultrastruct Res 1976; 55: 79-86.
36. Squier CA. Membrane coating granules in nonkeratinizing oral epithelium. J Ultrastruct Res 1977; 60: 212-20.
37. Wearley LL. Recent progress in protein and peptide delivery by noninvasive routes. Crit Rev Ther Drug Carrier Syst 1991; 8: 331-94.
38. Stratford RE, Jr., Lee VH. Aminopeptidase activity in albino rabbit extraocular tissues relative to the small intestine. J Pharm Sci 1985; 74: 731-4.
39. Kashi SD, Lee VH. Enkephalin hydrolysis in homogenates of various absorptive mucosae of the albino rabbit: similarities in rates and involvement of aminopeptidases. Life Sci 1986; 38: 2019-28.
40. Thomson PJ, Potten CS, Appleton DR. Mapping dynamic epithelial cell proliferative activity within the oral cavity of man: a new insight into carcinogenesis? Br J Oral Maxillofac Surg 1999; 37: 377-83.
41. Zimmer R, Ashburn MA. Noninvasive drug delivery. Compr Ther 2001; 27: 293-301.
42. Bruschi ML, de Freitas O. Oral bioadhesive drug delivery systems. Drug Dev Ind Pharm 2005; 31: 293-310.
43. Mandel ID. Biochemical aspects of calculus formation. II. Comparative studies of saliva in heavy and light calculus formers. J Periodontal Res 1974; 9: 211-21.
44. Rathbone MJ, Drummond B, Tucker I. Oral cavity as a site for systemic drug delivery. Adv. Drug Deliv. rev. 1994; 13: 1-22.
45. Levine MJ, Reddy MS, Tabak LA, et al. Structural aspects of salivary glycoproteins. J Dent Res 1987; 66: 436-41.
46. Marriot C. Gregory N, Eds. Bioadhesive Drug Delivery Systems. Boca Raton: CRC Press 1990.
47. Peppas NA, Sahlin JJ. Hydrogels as mucoadhesive and bioadhesive materials: a review. Biomaterials 1996; 17: 1553-61.
48. Tabak LA, Levine MJ, Mandel ID, Ellison SA. Role of salivary mucins in the protection of the oral cavity. J Oral Pathol 1982; 11: 1-17.
49. Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm 2009; 71: 505-18.
50. Harding SE, Creeth JM. Polyelectrolyte behaviour in mucus glycoproteins. Biochim Biophys Acta 1983; 746: 114-9.
51. Harding SE, Rowe AJ, Creeth JM. Further evidence for a flexible and highly expanded spheroidal model for mucus glycoproteins in solution. Biochem J 1983; 209: 893-6.
52. Khutoryanskiy VV. Advances in mucoadhesion and mucoadhesive polymers. Macromol Biosci 2011; 11: 748-64.
53. Gandhi RB, Robinson JR. Bioadhesion in drug delivery. Ind J Pharm Sci 1988; 81: 145-52.
54. Khanvilkar K, Donovan MD, Flanagan DR. Drug transfer through mucus. Adv Drug Deliv Rev 2001; 48: 173-93.
55. Sankar V, Hearnden V, Hull K, et al. Local drug delivery for oral mucosal diseases: challenges and opportunities. Oral Dis 2011; 17 Suppl 1: 73-84.
56. Hearnden V, Sankar V, Hull K, et al. New developments and opportunities in oral mucosal drug delivery for local and systemic disease. Adv Drug Deliv Rev 2012; 64(1): 16-28.
57. Scholz OA, Wolff A, Schumacher A, et al. Drug delivery from the oral cavity: focus on a novel mechatronic delivery device. Drug Discov Today 2008; 13: 247-53.
58. Mirth DB. Controlled-release therapeutic systems: technology applicable to the treatment of oral disease. Adv Dent Res 1987; 1: 109-18.
59. Hiremath PS, Bhonsle SA, Thumma S, Vemulapalli V. Recent patents on oral combination drug delivery and formulations. Recent Pat Drug Deliv Formul 2011; 5: 52-60.
60. Lee JW, Park JH, Robinson JR. Bioadhesive-based dosage forms: the next generation. J Pharm Sci 2000; 89: 850-66.
61. Chickering III D.E., Mathiowitz E., Bioadhesive drug delivery systems. Fundamentals, novel approaches, and developments. In Mathiowitz E, Chickering III DE, Lehr CM. Eds., Definitions mechanisms and theories of bioadhesion. New York: Marcel Dekker 1999, pp. 1-10.
62. Kinloch A. The science of adhesion, J Mater Sci 1980; 15: 2141-66.
63. Dodou D, Breedveld P, Wieringa PA. Mucoadhesives in the gastrointestinal tract: revisiting the literature for novel applications. Eur J Pharm Biopharm 2005; 60: 1-16.
64. Ugwoke MI, Agu RU, Verbeke N, Kinget R. Nasal mucoadhesive drug delivery: background, applications, trends and future perspectives. Adv Drug Deliv Rev 2005; 57: 1640-65.
65. Park K, Robinson J. Bioadhesive polymers as platforms for oralcontrolled drug delivery: method to study bioadhesion. Int. J Pharm1984; 19: 107-27.
66. Ludwig A. The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev 2005; 57: 1595-639.
67. Singla AK, Chawla M, Singh A. Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: a review. Drug Dev Ind Pharm 2000; 26: 913-24.
68. Khutoryanskiy VV. Hydrogen-bonded interpolymer complexes as materials for pharmaceutical applications. Int J Pharm 2007; 334: 15-26.
69. Fefelova NA, Nurkeeva ZS, Mun GA, Khutoryanskiy VV. Mucoadhesive interactions of amphiphilic cationic copolymers based on [2-(methacryloyloxy)ethyl]trimethylammonium chloride. Int J Pharm 2007; 339: 25-32.
70. Sogias IA, Williams AC, Khutoryanskiy VV. Why is chitosan mucoadhesive? Biomacromolecules 2008; 9: 1837-42.
71. Keely S, Rullay A, Wilson C, et al. In vitro and ex vivo intestinal tissue models to measure mucoadhesion of poly (methacrylate) and N-trimethylated chitosan polymers. Pharm Res 2005; 22: 38-49.
72. Soane RJ, Frier M, Perkins AC, Jones NS, Davis SS, Illum L. Evaluation of the clearance characteristics of bioadhesive systems in humans. Int J Pharm 1999; 178: 55-65.
73. Bravo-Osuna I, Ferrero C, Jimenez-Castellanos MR. Influence of moisture content on the mechanical properties of methyl methacrylate-starch copolymers. Eur J Pharm Biopharm 2007; 66: 63-72.
74. Bravo-Osuna I, Vauthier C, Farabollini A, Palmieri GF, Ponchel G. Mucoadhesion mechanism of chitosan and thiolated chitosanpoly(isobutyl cyanoacrylate) core-shell nanoparticles. Biomaterials 2007; 28: 2233-43.
75. Qu X, Khutoryanskiy VV, Stewart A, et al. Carbohydrate-based micelle clusters which enhance hydrophobic drug bioavailability by up to 1 order of magnitude. Biomacromolecules 2006; 7: 3452-9.
76. Qu XH, Wu Q, Zhang KY, Chen GQ. In vivo studies of poly(3- hydroxybutyrate-co-3-hydroxyhexanoate) based polymers: biodegradation and tissue reactions. Biomaterials 2006; 27: 3540-8.
77. Sajomsang W, Tantayanon S, Tangpasuthadol V, Daly WH. Quaternization of N-aryl chitosan derivatives: synthesis, characterization, and antibacterial activity. Carbohydr Res 2009; 344: 2502-11.
78. Rekha MR, Sharma CP. Synthesis and evaluation of lauryl succinyl chitosan particles towards oral insulin delivery and absorption. J Control Release 2009; 135: 144-51.
79. Lis H, Sharon N. Lectins as molecules and as tools. Annu Rev Biochem 1986; 55: 35-67.
80. Lehr CM. Lectin-mediated drug delivery: the second generation of bioadhesives. J Control Release 2000; 65: 19-29.
81. Clark MA, Hirst BH, Jepson MA. Lectin-mediated mucosal delivery of drugs and microparticles. Adv Drug Deliv Rev 2000; 43: 207-23.
82. Bernkop-Schnurch A. Mucoadhesive polymers: strategies, achievements and future challenges. Adv Drug Deliv Rev 2005; 57: 1553-5.
83. Guggi D, Marschutz MK, Bernkop-Schnurch A. Matrix tablets based on thiolated poly(acrylic acid): pH-dependent variation in disintegration and mucoadhesion. Int J Pharm 2004; 274: 97-105.
84. 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: 79-85.
85. Schmitz T, Hombach J, Bernkop-Schnurch A. Chitosan-N-acetyl cysteine conjugates: in vitro evaluation of permeation enhancing and P-glycoprotein inhibiting properties. Drug Deliv 2008; 15: 245-52.
86. Bernkop-Schnurch A, Clausen AE, Hnatyszyn M. Thiolated polymers: synthesis and in vitro evaluation of polymer-cysteamine conjugates. Int J Pharm 2001; 226: 185-94.
87. Bernkop-Schnurch A, Zarti H, Walker GF. Thiolation of polycarbophil enhances its inhibition of intestinal brush border membrane bound aminopeptidase N. J Pharm Sci 2001; 90: 1907-14.
88. Sakloetsakun D, Hombach JM, Bernkop-Schnurch A. In situ gelling properties of chitosan-thioglycolic acid conjugate in the presence of oxidizing agents. Biomaterials 2009; 30: 6151-7.
89. Kafedjiiski K, Hoffer M, Werle M, Bernkop-Schnurch A. Improved synthesis and in vitro characterization of chitosanthioethylamidine conjugate. Biomaterials 2006; 27: 127-35.
90. Albrecht K, Greindl M, Kremser C, Wolf C, Debbage P, Bernkop-Schnurch A. Comparative in vivo mucoadhesion studies of thiomer formulations using magnetic resonance imaging and fluorescence detection. J Control Release 2006; 115: 78-84.
91. Grabovac V, Guggi D, Bernkop-Schnurch A. Comparison of the mucoadhesive properties of various polymers. Adv Drug Deliv Rev 2005; 57: 1713-23.
92. Davidovich-Pinhas M, Bianco-Peled H. Alginate-PEGAc: a new mucoadhesive polymer. Acta Biomater 2011; 7: 625-33.
93. Davidovich-Pinhas M, Bianco-Peled H. Novel mucoadhesive system based on sulfhydryl-acrylate interactions. J Mater Sci Mater Med 2010; 21: 2027-34.
94. Chen CZ, Beck-Tan NC, Dhurjati P, van Dyk TK, LaRossa RA, Cooper SL. Quaternary ammonium functionalized poly(propylene imine) dendrimers as effective antimicrobials: structure-activity studies. Biomacromolecules 2000; 1: 473-80.
95. Navath RS, Kurtoglu YE, Wang B, Kannan S, Romero R, Kannan RM. Dendrimer-drug conjugates for tailored intracellular drug release based on glutathione levels. Bioconjug Chem 2008; 19: 2446-55.
96. Vandamme TF, Brobeck L. Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release 2005; 102: 23-38.
97. Ivanov AE, Nilsson L, Galaev IY, Mattiasson B. Boronatecontaining 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: 36-43.
98. Ladmiral V, Mantovani G, Clarkson GJ, Cauet S, Irwin JL, Haddleton DM. Synthesis of neoglycopolymers by a combination of click chemistry and living radical polymerization. J Am Chem Soc 2006; 128: 4823-30.
99. Rihova B, Rathi RC, Kopeckova P, Kopecek J. Bioadhesive polymers for oral drug delivery. Adv Exp Med Biol 1995; 371B: 1491-4.
100. Watanabe J, Yakou S, Takayama K, Machida Y, Nagai T. Drug release behaviors from hydrogel prepared with water soluble dietary fibers. J Pharm Sci Techn Jpn 1991; 51: 29-35.
101. Shojaei AH, Zhuo SL, Li X. Transbuccal delivery of acyclovir (II): feasibility, system design, and in vitro permeation studies. J Pharm Pharm Sci 1998; 1: 66-73.
102. Ceschel GC, Maffei P, Lombardi Borgia S, Ronchi C. Design and evaluation of buccal adhesive hydrocortisone acetate (HCA) tablets. Drug Deliv 2001; 8: 161-71.
103. Ikinci G, Senel S, Wilson CG, Sumnu M. Development of a buccal bioadhesive nicotine tablet formulation for smoking cessation. Int J Pharm 2004; 277: 173-8.
104. Shojaei AH, Li X. Novel copolymers of acrylic acid and poly ethylene glycol monomethylether monomethacrylate for bccal mucoadhesion: Preparation and surface characterization. Pharm Res 1995; 12: S210.
105. Shojaei AH, Paulson J, Honary S. Evaluation of poly(acrylic acid-co-ethylhexyl acrylate) films for mucoadhesive transbuccal drug delivery: factors affecting the force of mucoadhesion. J Control Release 2000; 67: 223-32.
106. Varshosaz J, Dehghan Z. Development and characterization of buccoadhesive nifedipine tablets. Eur J Pharm Biopharm 2002; 54: 135-41.
107. Akbari J, Nokhodchi A, Farid D, Adrangui M, Siahi-Shadbad MR, Saeedi M. Development and evaluation of buccoadhesive propranolol hydrochloride tablet formulations: effect of fillers. Farmaco 2004; 59: 155-61.
108. Desai D, Rinaldi F, Kothari S, et al. Effect of hydroxypropyl cellulose (HPC) on dissolution rate of hydrochlorothiazide tablets. Int J Pharm 2006; 308: 40-5.
109. Giannola LI, De Caro V, Giandalia G, et al. Diffusion of naltrexone across reconstituted human oral epithelium and histomorphological features. Eur J Pharm Biopharm 2007; 65: 238-46.
110. Carlo Ceschel G, Bergamante V, Calabrese V, Biserni S, Ronchi C, Fini A. Design and evaluation in vitro of controlled release mucadhesive tablets containing chlorhexidine. Drug Dev Ind Pharm 2006; 32: 53-61.
111. Llabot JM, Manzo RH, Allemandi DA. Double-layered mucoadhesive tablets containing nystatin. AAPS Pharm Sci Tech 2002; 3: E22.
112. Shanker G, Kumar CK, Gonugunta CS, Kumar BV, Veerareddy PR. Formulation and evaluation of bioadhesive buccal drug delivery of tizanidine hydrochloride tablets. AAPS Pharm Sci Tech 2009; 10: 530-9.
113. Vazquez JA, Patton LL, Epstein JB, et al. Randomized, comparative, double-blind, double-dummy, multicenter trial of miconazole buccal tablet and clotrimazole troches for the treatment of oropharyngeal candidiasis: study of miconazole Lauriad(R) efficacy and safety (SMiLES). HIV Clin Trials 2010; 11: 186-96.
114. Cilurzo F, Gennari CG, Selmin F, et al. A new mucoadhesive dosage form for the management of oral lichen planus: formulation study and clinical study. Eur J Pharm Biopharm 2010; 76: 437-42.
115. Nakane S, Kakumoto M, Yukimatsu K, Chien YW. Oramucosal delivery of LHRH: pharmacokinetic studies of controlled and enhanced transmucosal permeation. Pharm Dev Technol 1996; 1: 251-9.
116. Park CR, Munday DL. Development and evaluation of a biphasic buccal adhesive tablet for nicotine replacement therapy. Int J Pharm 2002; 237: 215-26.
117. Rathbone MJ, Eds. Oral Mucosal Drug Delivery. New York: Mercel Dekker, Inc. 1996.
118. Beyssac E, Touaref F, Meyer M, Jacob L, Sandouk P, Aiache JM. Bioavailability of morphine after administration of a new bioadhesive buccal tablet. Biopharm Drug Dispos 1998; 19: 401-5.
119. Ikinci G, Capan Y, Senel S, Alaaddinoglu E, Dalkara T, Hincal AA. In vitro/in vivo studies on a buccal bioadhesive tablet formulation of carbamazepine. Pharmazie 2000; 55: 762-5.
120. Benes L, Claustrat B, Horriere F, et al. Transmucosal, oral controlled-release, and transdermal drug administration in human subjects: a crossover study with melatonin. J Pharm Sci 1997; 86: 1115-9.
121. Guggi D, Bernkop-Schnurch A. In vitro evaluation of polymeric excipients protecting calcitonin against degradation by intestinal serine proteases. Int J Pharm 2003; 252: 187-96.
122. Guggi D, Kast CE, Bernkop-Schnurch A. In vivo evaluation of an oral salmon calcitonin-delivery system based on a thiolated chitosan carrier matrix. Pharm Res 2003; 20: 1989-94.
123. Guggi D, Krauland AH, Bernkop-Schnurch A. Systemic peptide delivery via the stomach: in vivo evaluation of an oral dosage form for salmon calcitonin. J Control Release 2003; 92: 125-35.
124. Senel S, Ikinci G, Kas S, Yousefi-Rad A, Sargon MF, Hincal AA. Chitosan films and hydrogels of chlorhexidine gluconate for oral mucosal delivery. Int J Pharm 2000; 193: 197-203.
125. Guo JH, Cooklock KM. The effects of backing materials and multilayered systems on the characteristics of bioadhesive buccal patches. J Pharm Pharmacol 1996; 48: 255-7.
126. Li C, Bhatt PP, Johnston TP. Evaluation of a mucoadhesive buccal patch for delivery of peptides: in vitro screening of bioadhesion. Drug Dev Ind Pharm 1998; 24: 919-26.
127. Guo JH. Investigating the surface properties and bioadhesion of buccal patches. J Pharm Pharmacol 1994; 46: 647-50.
128. Ishida M, Machida Y, Nambu N, Nagai T. New mucosal dosage form of insulin. Chem Pharm Bull (Tokyo) 1981; 29: 810-6.
129. Anders R, Merkle HP, Schurr W, Ziegler R. Buccal absorption of protirelin: an effective way to stimulate thyrotropin and prolactin. J Pharm Sci 1983; 72: 1481-3.
130. Robinson JR, Longer MA, Veillard M. Bioadhesive polymers for controlled drug delivery. Ann N Y Acad Sci 1987; 507: 307-14.
131. Eaimtrakarn S, Rama Prasad YV, Puthli SP, Yoshikawa Y, Shibata N, Takada K. Possibility of a patch system as a new oral delivery system. Int J Pharm 2003; 250: 111-7.
132. Stecker SS, Swift JQ, Hodges JS, Erickson PR. Should a mucoadhesive patch (DentiPatch) be used for gingival anesthesia in children? Anesth Prog 2002; 49: 3-8.
133. 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: 318-25.
134. Malik IA, Moid I, Haq S, Sabih M. A double-blind, placebocontrolled, randomized trial to evaluate the role of tetrachlorodecaoxide in the management of chemotherapy-induced oral mucositis. J Pain Symptom Manage 1997; 14: 82-7.
135. 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: 2935.
136. Ali J, Khar R, Ahuja A, Kalra R. Buccoadhesive erodible disk for treatment of oro-dental infections: design and characterisation. Int J Pharm 2002; 238: 93-103.
137. Meng W, Dong Y, Liu J, et al. A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial. Trials 2009; 10: 30.
138. Wong CF, Yuen KH, Peh KK. An in-vitro method for buccal adhesion studies: importance of instrument variables. Int J Pharm 1999; 180: 47-57.
139. Needleman IG, Martin GP, Smales FC. Characterisation of bioadhesives for periodontal and oral mucosal drug delivery. J Clin Periodontol 1998; 25: 74-82.
140. Bansal K, Rawat MK, Jain A, Rajput A, Chaturvedi TP, Singh S. Development of satranidazole mucoadhesive gel for the treatment of periodontitis. AAPS Pharm Sci Tech 2009; 10: 716-23.
141. Vinholis AH, Figueiredo LC, Marcantonio Junior E, Marcantonio RA, Salvador SL, Goissis G. Subgingival utilization of a 1% chlorhexidine collagen gel for the treatment of periodontal pockets. A clinical and microbiological study. Braz Dent J 2001; 12: 209-13.
142. Skulason S, Holbrook WP, Kristmundsdottir T. Clinical assessment of the effect of a matrix metalloproteinase inhibitor on aphthous ulcers. Acta Odontol Scand 2009; 67: 25-9.
143. Favia G, Mariggio MA, Maiorano F, Cassano A, Capodiferro S, Ribatti D. Accelerated wound healing of oral soft tissues and angiogenic effect induced by a pool of aminoacids combined to sodium hyaluronate (AMINOGAM). J Biol Regul Homeost Agents 2008; 22: 109-16.
144. Campisi G, Giandalia G, De Caro V, Di Liberto C, Arico P, Giannola LI. A new delivery system of clobetasol-17-propionate (lipidloaded microspheres 0.025%) compared with a conventional formulation (lipophilic ointment in a hydrophilic phase 0.025%) in topical treatment of atrophic/erosive oral lichen planus. A Phase IV, randomized, observer-blinded, parallel group clinical trial. Br J Dermatol 2004; 150: 984-90.
145. Sankar V, Hearnden V, Hull K, et al. Local drug delivery for oral mucosal diseases: challenges and opportunities. Oral Dis 2011; 17 (Suppl 1): 73-84.
146. Colella G, Cannavale R, Vicidomini A, Rinaldi G, Compilato D, Campisi G. Efficacy of a spray compound containing a pool of collagen precursor synthetic aminoacids (l-proline, l-leucine, l-lysine and glycine) combined with sodium hyaluronate to manage chemo/radiotherapy-induced oral mucositis: preliminary data of an open trial. Int J Immunopathol Pharmacol 2010; 23: 143-51.
147. Guevara-Aguirre J, Guevara M, Saavedra J, Mihic M, Modi P. Oral spray insulin in treatment of type 2 diabetes: a comparison of efficacy of the oral spray insulin (Oralin) with subcutaneous (SC) insulin injection, a proof of concept study. Diabetes Metab Res Rev 2004; 20: 472-8.
148. Svensson O, Arnebrant T. Adsorption of serum albumin on silica-- the influence of surface cleaning procedures. J Colloid Interface Sci 2010; 344: 44-7.
149. Kockisch S, Rees GD, Young SA, Tsibouklis J, Smart JD. A directstaining method to evaluate the mucoadhesion of polymers from aqueous dispersion. J Control Release 2001; 77: 1-6.
150. Park K, Robinson J. Bioadhesive polymers as platforms for oralcontrolled drug delivery: method to study bioadhesion. Int J Pharm 1984; 19: 107-27.
151. Park H, Robinson JR. Mechanisms of mucoadhesion of poly (acrylic acid) hydrogels. Pharm Res 1987; 4: 457-64.