Thiomers: The next generation of mucoadhesive polymers

American Journal of Drug Delivery

Volumn 3, Issue 3, 2005, Pages 141-154

  Bernkop Schnürch, Andreas ^a   Greimel, Alexander ^a  

^a UNIVERSITY OF INNSBRUCK   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ALGINATE CYSTEINE; CARBOXYMETHYLCELLULOSE CYSTEINE; CHITOSAN; CHITOSAN 4 THIOBUTYLAMIDINE; CHITOSAN CYSTEINE; CHITOSAN THIIOGLYCOLIC ACID; CHITOSAN THIOETHYLAMIDINE; CHITOSAN THIOGLYCOLIC ACID; DRUG CARRIER; EXCIPIENT; EYE DROPS; FLUORESCEIN; GLYCOPROTEIN; HUMAN GROWTH HORMONE; INSULIN; LOW MOLECULAR WEIGHT HEPARIN; PEPTIDASE; PEPTIDE; POLYACRYLIC ACID; POLYACRYLIC ACID 450 CYSTEINE; POLYACRYLIC ACID CYSTEINE; POLYACRYLIC ACID HOMOCYSTEINE; POLYCARBOPHIL; POLYCARBOPHIL CYSTEAMINE; POLYCARBOPHIL CYSTEINE; POLYMER; PROTEIN; SALCATONIN; THIOL DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CELL ADHESION; CHEMICAL MODIFICATION; CORNEA; COVALENT BOND; DIFFUSION CHAMBER; DISULFIDE BOND; DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG PENETRATION; DRUG SAFETY; DRUG STABILITY; DRUG SYNTHESIS; DRUG TRANSPORT; ENZYME INHIBITION; ENZYME RELEASE; GEL; HUMAN; HYDROPHILICITY; IN VIVO STUDY; MUCOSA; NONHUMAN; PARTICLE SIZE; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; REVIEW; SUSTAINED DRUG RELEASE; TABLET;

EID: 31144449387     PISSN: 11759038     EISSN: 11759038     Source Type: Journal    
DOI: 10.2165/00137696-200503030-00001     Document Type: Review

References (134)

1. Khosla R, Davis SS. The effect of polycarbophil on the gastric emptying of pellets. J Pharm Pharmacol 1987 Jan; 39 (1): 47-9
2. Lehr CM. From sticky stuff to sweet receptors: achievements, limits and novel approaches to bioadhesion. Eur J Drug Metab Pharmacokinet 1996 Apr-Jun; 21 (2): 139-48
3. Bernkop-Schnürch A, Schwarz V, Steininger S. Polymers with thiol groups: a new generation of mucoadhesive polymers? Pharm Res 1999 Jun; 16 (6): 876-81
4. Bernkop-Schnürch A, Steininger S. Synthesis and characterisation of mucoadhesive thiolated polymers. Int J Pharm 2000 Jan; 194 (2): 239-47
5. Clausen AE, Bernkop-Schnürch A. In vitro evaluation of the permeation-enhancing effect of thiolated polycarbophil. J Pharm Sci 2000 Oct; 89 (10): 1253-61
6. Bernkop-Schnürch A, Zarti H, Walker GF. Thiolation of polycarbophil enhances its inhibition of soluble and intestinal brush border membrane bound aminopeptidase N. J Pharm Sci 2001 Nov; 90 (11): 1907-14
7. Bromberg L. Intelligent polyelectrolytes and gels in oral drug delivery. Curr Pharm Biotechnol 2003 Oct; 4 (5): 339-49
8. Bernkop-Schnürch A. Mucoadhesive polymers. In: Dumitriu S, editor. Polymeric biomaterials. 2nd ed. New York: Marcel Dekker, 2002: 147-65
9. Campbell BJ. Biochemical and functional aspects of mucus and mucin-type glycoproteins. In: Mathiowitz E, Chickering DE, Lehr CM, editors. Bioadhesive drug delivery systems. New York: Marcel Dekker, 1999: 85
10. Gum JR, Hicks JW, Toribara NW, et al. The human MUC2 intestinal mucin has cysteine-rich subdomains located both upstream and downstream of its central repetitive region. J Biol Chem 1992 Oct; 267 (30): 21375-83
11. Matthes I, Nimmerfall F, Sucker H. Mucus models for investigation of intestinal absorption mechanisms: 1. validation and optimization of the model. Pharmazie 1992 Jul; 47 (7): 505-15
12. Bansil R, Stanley E, LaMont JT. Mucin biophysics. Annu Rev Physiol 1995; 57: 635-57
13. Gendler SJ, Spicer AP. Epithelial mucin genes. Annu Rev Physiol 1995; 57: 607-34
14. Tabak LA. In defense of the oral cavity: structure, biosynthesis and function of salivary mucins. Annu Rev Physiol 1995; 57: 547-64
15. Allen A, Hutton DA, Pearson JP, et al. Mucus glycoprotein structure, gel formation and gastrointestinal mucus function. In: Nugent J, O'Connor M, editors. London: Ciba Foundation Symposium, 1984; 109: 137-56
16. Warren SJ, Kellaway IW. The synthesis and in vitro characterization of the mucoadhesion and swelling of poly(acrylic acid) hydrogels. Pharm Dev Technol 1998 May; 3 (2): 199-208
17. Park H, Robinson JR. Mechanisms of mucoadhesion of poly(acrylic acid) hydrogels. Pharm Res 1987 Dec; 4 (6): 457-64
18. Peppas NA, Buri PA. Surface, interfacial and molecular aspects of polymer adhesion on soft tissues. J Control Release 1985; 2: 257-75
19. Madsen F, Eberth K, Smart JD. A rheological assessment of the nature of interactions between mucoadhesive polymers and a homogenised mucus gel. Biomaterials 1998 Jun; 19 (11-12): 1083-92
20. Herrero-Vanrell R, Fernandez-Carballido A, Frutos G, et al. Enhancement of the mydriatic response to tropicamide by bioadhesive polymers. J Ocul Pharmacol Ther 2000 Oct; 16 (5): 419-28
21. Esposito P, Colombo I, Lovrecich M. Investigation of surface properties of some polymers by a thermodynamic and mechanical approach: possibility of predicting mucoadhesion and biocompatibility. Biomaterials 1994 Feb; 15 (3): 177-82
22. Nafee NA, Ismail FA, Boraie NA, et al. Mucoadhesive delivery systems: I. Evaluation of mucoadhesive polymers for buccal tablet formulation. Drug Dev Ind Pharm 2004; 30 (9): 985-93
23. Patel MM, Smart JD, Nevell TG, et al. Mucin/poly(acrylic acid) interactions: a spectroscopic investigation of mucoadhesion. Biomacromolecules 2003 Sep-Oct; 4 (5): 1184-90
24. Mizrahi B, Golenser J, Wolnerman JS, et al. Adhesive tablet effective for treating canker sores in humans. J Pharm Sci 2004 Dec; 93 (12): 2927-35
25. Bogataj M, Vovk T, Kerec M, et al. The correlation between zeta potential and mucoadhesion strength on pig vesical mucosa. Biol Pharm Bull 2003 May; 26 (5): 743-6
26. Kockisch S, Rees GD, Tsibouklis J, et al. Mucoadhesive, triclosan-loaded polymer microspheres for application to the oral cavity: preparation and controlled release characteristics. Eur J Pharm Biopharm 2005 Jan; 59 (1): 207-16
27. Kawashima Y, Yamamoto H, Takeuchi H, et al. Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm Dev Technol 2000; 5 (1): 77-85
28. Takeuchi H, Yamamoto H, Niwa T, et al. Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes. Pharm Res 1996 Jun; 13 (6): 896-901
29. Jain SK, Chourasia MK, Jain AK, et al. Development and characterization of mucoadhesive microspheres bearing salbutamol for nasal delivery. Drug Deliv 2004 Mar-Apr; 11 (2): 113-22
30. Jadhav BK, Khandelwal KR, Ketkar AR, et al. Formulation and evaluation of mucoadhesive tablets containing eugenol for the treatment of periodontal diseases. Drug Dev Ind Pharm 2004 Feb; 30 (2): 195-203
31. Chary RB, Vani G, Rao YM. In vitro and in vivo adhesion testing of mucoadhesive drug delivery systems. Drug Dev Ind Pharm 1999 May; 25 (5): 685-90
32. Tafaghodi M, Abolghasem Sajadi Tabassi S, Jaafari MR, et al. Evaluation of the clearance characteristics of various microspheres in the human nose by gamma-scintigraphy. Int J Pharm 2004 Aug; 280 (1-2): 125-35
33. Saso L, Bonanni G, Grippa E, et al. Interaction of hyaluronic acid with mucin, evaluated by gel permeation chromatography. Res Commun Mol Pathol Pharmacol 1999; 104 (3): 277-84
34. Lim ST, Martin GP, Berry DJ, et al. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. J Control Release 2000 May; 66 (2-3): 281-92
35. Lim ST, Forbes B, Martin GP, et al. In vivo and in vitro characterization of novel microparticulates based on hyaluronan and chitosan hydroglutamate. AAPS PharmSciTech 2001 Oct; 2 (4): 20
36. Di Colo G, Burgalassi S, Chetoni P, et al. Relevance of polymer molecular weight to the in vitro/in vivo performances of ocular inserts based on poly(ethylene oxide). Int J Pharm 2001 Jun; 220 (1-2): 169-77
37. Sahlin JJ, Peppas NA. Enhanced hydrogel adhesion by polymer interdiffusion: use of linear poly(ethylene glycol) as an adhesion promoter. J Biomater Sci Polym Ed 1997; 8 (6): 421-36
38. Abd El-Hameed MD, Kellaway IW. Preparation and in vitro characterisation of mucoadhesive polymeric microspheres as intra-nasal delivery systems. Eur J Pharm Biopharm 1997 Jul; 44 (1): 53-60
39. Oechsner M, Keipert S. Polyacrylic acid/polyvinylpyrrolidone bipolymeric systems: I. Rheological and mucoadhesive properties of formulations potentially useful for the treatment of dry-eye-syndrome. Eur J Pharm Biopharm 1999 Mar; 47 (2): 113-8
40. Otto S, Roth HW. Effectiveness and tolerance of a polyvidon substance in treatment of dry eye syndromes. Klin Monatsbl Augenheilkd 1996 Dec; 209 (6): 362-7
41. 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
42. Woodley J. Bioadhesion: new possibilities for drug administration? Clin Pharmacokinet 2001; 40 (2): 77-84
43. Bernkop-Schnürch A, Gilge B. Anionic mucoadhesive polymers as auxiliary agents for the peroral administration of (poly)peptide drugs: influence of the gastric juice. Drug Dev Ind Pharm 2000 Feb; 26 (2): 107-13
44. Borchard G, Luessen HL, de Boer AG, et al. The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption: III: effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro. J Control Release 1996; 39 (2): 131-8
45. Leitner VM, Walker GF, Bernkop-Schnürch A. Thiolated polymers: evidence for the formation of disulphide bonds with mucus glycoproteins. Eur J Pharm Biopharm 2003 Sep; 56 (2): 207-14
46. Bernkop-Schnürch A, Clausen AE, Hnatyszyn M. Thiolated polymers: synthesis and in vitro evaluation of polymer-cysteamine conjugates. Int J Pharm 2001; 226: 185-94
47. Bernkop-Schnürch A, Kast CE, Richter MF. Improvement in the mucoadhesive properties of alginate by the covalent attachment of cysteine. J Control Release 2001; 71: 277-85
48. Bernkop-Schnürch A, Leitner VM, Moser V. Synthesis and in vitro characterisation of a poly(acrylic acid)-homocysteine conjugate. Drug Dev Ind Pharm 2004; 30: 1-8
49. Ellman GL, Gan GL. Sulfhydryl groups in Nissl bodies. Exp Brain Res 1969; 9 (3): 261-8
50. Felt O, Buri P, Gurny R. Chitosan: a unique polysaccharide for drug delivery. Drug Dev Ind Pharm 1998 Nov; 24 (11): 979-93
51. Bernkop-Schnürch A, Brandt UM, Clausen AE. Synthesis and in vitro evaluation of chitosan-cysteine conjugates. Sci Pharm 1999; 67: 196-208
52. Bernkop-Schnürch A, Hopf TE. Synthesis and in vitro evaluation of chitosan-thioglycolic acid conjugates. Sci Pharm 2001; 69: 109-18
53. Bernkop-Schnürch A, Hornof M, Zoidl T. Thiolated polymers -thiomers: synthesis and in vitro evaluation of chitosan-2-iminothiolane conjugates. Int J Pharm 2003 Jul; 260 (2): 229-37
54. Kafedjiiski K, Krauland AH, Hoffer MH, et al. Synthesis and in vitro evaluation of a novel thiolated chitosan. Biomaterials 2005 Mar; 26 (7): 819-26
55. Kast CE, Bernkop-Schnürch A. Thiolated polymers-thiomers: development and in vitro evaluation of chitosan-thioglycolic acid conjugates. Biomaterials 2001 Sep; 22 (17): 2345-52
56. Marschütz MK, Bernkop-Schnürch A. Thiolated polymers: self-crosslinking properties of thiolated 450 kDa poly(acrylic acid) and their influence on mucoadhesion. Eur J Pharm Sci 2002; 15: 387-94
57. Roldo M, Hornof M, Caliceti P, et al. Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation. Eur J Pharm Biopharm 2004; 57: 115-21
58. Bernkop-Schnürch A, Guggi D, Pinter Y. Thiolated chitosans: development and in vivo evaluation of a mucoadhesive, permeation enhancing oral drug delivery system. J Control Release 2004 Jan; 94 (1): 177-86
59. Leitner VM, Marschütz MK, Bernkop-Schnürch A. Mucoadhesive and cohesive properties of poly(acrylic acid)-cysteine conjugates with regard to their molecular mass. Eur J Pharm Sci 2003 Jan; 18 (1): 89-96
60. Guggi D, Marschütz MK, Bernkop-Schnürch A. Matrix tablets based on thiolated poly(acrylic acid): pH-dependent variation in disintegration and mucoadhesion. Int J Pharm 2004; 274: 97-105
61. Hutton DA, Pearson JP, Allen A, et al. Mucolysis of the colonic mucus barrier by faecal proteinases: inhibition by interacting polyacrylate. Clin Sci 1990; 78: 265-71
62. Luessen HL, de Leeuw BJ, Perard D, et al. Mucoadhesive polymers in peroral peptide drug delivery: I. influence of mucoadhesive excipients on the proteolytic activity of intestinal enzymes. Eur J Pharm Sci 1996 Mar; 4 (2): 117-28
63. Bernkop-Schnürch A, Thaler SC. Polycarbophil-cysteine conjugates as platforms for oral polypeptide delivery systems. J Pharm Sci 2000; 89: 901-9
64. Valenta C, Marschütz MK, Egyed C, et al. Evaluation of the inhibitory effect of thiolated poly(acrylates) on vaginal membrane bound aminopeptidase N. J Pharm Pharmacol 2001; 54: 603-10
65. Langoth N, Kalbe J, Bernkop-Schnürch A. Development of buccal drug delivery systems based on a thiolated polymer. Int J Pharm 2003; 252: 141-8
66. Riley RG, Green KL, Smart JD, et al. The gastrointestinal transit profile of 14C-labelled poly(acrylic acids): an in vivo study. Biomaterials 2001 Jul; 22 (13): 1861-7
67. Clausen AE, Kast CE, Bernkop-Schnürch A. The role of glutathione in the permeation enhancing effect of thiolated polymers. Pharm Res 2002 May; 19 (5): 602-8
68. Leitner VM, Guggi D, Bernkop-Schnürch A. Thiomers in non-invasive peptide delivery: in vitro and in vivo characterisation of a polycarbophil-cysteine/glutathione gel formulation for human growth hormone. J Pharm Sci 2004 Jul; 93 (7): 1682-91
69. Kast CE, Guggi D, Langoth N, et al. Development and in vivo evaluation of an oral delivery system for low molecular weight heparin based on thiolated polycarbophil. Pharm Res 2003 Jun; 20 (6): 931-6
70. Hornof MD, Bernkop-Schnürch A. In vitro evaluation of the permeation enhancing effect of polycarbophil-cysteine conjugates on the cornea of rabbits. J Pharm Sci 2002 Dec; 91 (12): 2588-92
71. Clausen AE, Bernkop-Schnürch A. Thiolated carboxymethylcellulose: in vitro evaluation of its permeation enhancing effect on peptide drugs. Eur J Pharm Biopharm 2001 Jan; 51 (1): 25-32
72. Kast CE, Bernkop-Schnürch A. Influence of the molecular mass on the permeation enhancing effect of different poly(acrylates). J Drug Del Sci Tech 2002; 12 (6): 351-6
73. Langoth N, Kalbe J, Bernkop-Schnürch A. Development and in vitro evaluation of a mucoadhesive and permeation enhancing buccal delivery system for PACAP. Int J Pharm 2005 May; 296 (1-2) 103-11
74. Collares-Buzato CB, Jepson MA, Simmons NL, et al. Increased tyrosine phosphorylation causes redistribution of adherens junction and tight junction proteins and perturbs paracellular barrier function in MDCK epithelia. Eur J Cell Biol 1998 Jun; 76 (2): 85-92
75. Barrett WC, DeGnore JP, Konig S, et al. Regulation of PTP1B via glutathionylation of the active site cysteine 215. Biochemistry 1999 May; 38 (20): 6699-705
76. Grafstrom R, Stead AH, Orrenius S. Metabolism of extracellular glutathione in rat small-intestinal mucosa. Eur J Biochem 1980 May; 106 (2): 571-7
77. Staddon JM, Herrenknecht K, Smales C, et al. Evidence that tyrosine phosphorylation may increase tight junction permeability. J Cell Sci 1995 Feb; 108 (Pt 2): 609-19
78. Guggi D, Bernkop-Schnürch A. Improved paracellular uptake by the combination of different types of permeation enhancers. Int J Pharm 2005 Jan; 288 (1): 141-50
79. Kast CE, Valenta C, Leopold M, et al. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J Control Release 2002 Jun; 81 (3): 347-54
80. Guggi D, Krauland AH, Bernkop-Schnürch A. Systemic peptide delivery via the stomach: in vivo evaluation of an oral dosage form for salmon calcitonin. J Control Release 2003 Sep; 92 (1-2): 125-35
81. Schmitz T, Leitner VM, Bernkop-Schnürch A. Oral heparin delivery: design and in vivo evaluation of a stomach-targeted mucoadhesive delivery system. J Pharm Sci 2005 May; 94 (5): 966-73
82. Clausen AE, Bernkop-Schnürch A. In vitro evaluation of matrix tablets based on thiolated polycarbophil. Pharm Ind 2001; 63: 312-7
83. Krauland AH, Bernkop-Schnürch A. Thiomers: development and in vitro evaluation of a peroral microparticulate peptide delivery system. Eur J Pharm Biopharm 2004 Mar; 57 (2): 181-7
84. Valenta C, Kast CE, Harich I, et al. Development and in vitro evaluation of a mucoadhesive vaginal delivery system for progesterone. J Control Release 2001; 77: 323-32
85. Paulsson M, Hägerström H, Edsman K. Rheological studies of the gelation of deacetylated gellan gum (Gelrite) in physiological conditions. Eur J Pharm Sci 1999; 9: 99-105
86. Krauland AH, Leitner VM, Bernkop-Schnürch A. Improvement in the in situ gelling properties of deacetylated gellan gum by the immobilization of thiol groups. J Pharm Sci 2003; 92: 1234-41
87. Hornof MD, Kast CE, Bernkop-Schnürch A. In vitro evaluation of the viscoelastic behavior of chitosan: thioglycolic acid conjugates. Eur J Pharm Biopharm 2003; 55: 185-90
88. Bernkop-Schnürch A, Hornof MD, Kast CE, et al. Thiolated polymers: stability of thiol moieties under different storage conditions. Sci Pharm 2002; 70: 331-9
89. Langoth N, Guggi D, Bernkop-Schnürch A. Investigation on the cytotoxicity of (thiolated) polyacrylates. Toxicol In Vitro 2005. In press
90. Guggi D, Langoth N, Hoffer MH, et al. Comparative evaluation of cytotoxicity of a glucosamine-TBA conjugate and a chitosan-TBA conjugate. Int J Pharm 2004 Jul; 278 (2): 353-60
91. Hornof M, Weyenberg W, Ludwig A, et al. Mucoadhesive ocular insert based on thiolated poly(acrylic acid): development and in vivo evaluation in humans. J Control Release 2003 May; 89 (3): 419-28
92. Caliceti P, Salmaso S, Walker G, et al. Development and in vivo evaluation of an oral insulin-PEG delivery system. Eur J Pharm Sci 2004 Jul; 22 (4): 315-23
93. Marschütz MK, Caliceti P, Bernkop-Schnürch A. Design and in vivo evaluation of an oral delivery system for insulin. Pharm Res 2000; 17: 1468-74
94. Krauland AH, Guggi D, Bernkop-Schnürch A. Oral insulin delivery: the potential of thiolated chitosan-insulin tablets on non-diabetic rats. J Control Release 2004 Mar; 95 (3): 547-55
95. Guggi D, Kast CE, Bernkop-Schnürch A. In vivo evaluation of an oral salmon calcitonin-delivery system based on a thiolated chitosan carrier matrix. Pharm Res 2003 Dec; 20 (12): 1989-94
96. Leitner VM, Guggi D, Krauland AH, et al. Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a thiomer/glutathione microparticulate delivery system. J Control Release 2004 Nov; 100 (1): 87-95
97. Lee YH, Sinko PJ. Oral delivery of salmon calcitonin. Adv Drug Deliv Rev 2000 Aug; 42 (3): 225-38
98. Buclin T, Cosma MR, Burkhardt P. Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers. J Bone Miner Res 2002; 17: 1478-85
99. Bernkop-Schnürch A, Hornof M, Guggi D. Thiolated chitosans. Eur J Pharm Biopharm 2004 Jan; 57 (1): 9-17
100. Shah RB, Ahsan F, Khan MA. Oral delivery of proteins: progress and prognostication. Crit Rev Ther Drug Carrier Syst 2002; 19 (2): 135-69
101. Luessen HL, Verhoef JC, Borchard G, et al. Mucoadhesive polymers in peroral peptide drug delivery: II. carbomer and polycarbophil are potent inhibitors of the intestinal proteolytic enzyme trypsin. Pharm Res 1995 Sep; 12 (9): 1293-8
102. Bai JP, Chang LL, Guo JH. Effects of polyacrylic polymers on the degradation of insulin and peptide drugs by chymotrypsin and trypsin. J Pharm Pharmacol 1996 Jan; 48 (1): 17-21
103. Hirsh J, Warkentin TE, Raschke R, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998; 114: 489-510
104. Thompson-Ford JK. Low-molecular-weight-heparin for the treatment of deep vein thrombosis. Pharmacotherapy 1998; 18: 748-58
105. Lee Y, Kim SH, Byun Y. Oral delivery of new heparin derivatives in rats. Pharm Res 2000; 17: 1259-64
106. Andriuoli G, Bossi M, Caramazza I, et al. Heparin by alternative routes of administration. Haemostasis 1990; 20 Suppl. 1: 154-8
107. Dal Pozzo A, Acquasaliente M, Geron MR. New heparin complexes active by intestinal absorption: I-multiple ion pairs with basic organic compounds. Thromb Res 1989; 56: 119-24
108. Caramazza I, D'Atri G, Bossi ML, et al. Intraduodenal absorption of the new UF-Heparin salt ITF 1057 in the conscious dog. Thromb Res 1991; 62: 785-9
109. Morton AK, Edwards HE, Allen JC, et al. An evaluation of the oral administration of commercial and fractionated heparin samples in rats. Int J Pharm 1981; 9: 321-35
110. Kim TD, Sakon M, Kawasaki T, et al. Studies on liposome-encapsulated heparin. Thromb Res 1986; 43: 603-12
111. Ueno M, Nakasaki T, Horikoshi I, et al. Oral administration of liposomally-entrapped heparin to beagle dogs. Chem Pharm Bull 1982; 30: 2245-7
112. Guarini S, Ferrari W. Sodium deoxycholate promotes the absorption of heparin administrated orally, probably by acting on gastrointestinal mucosa, in rats. Experientia 1985; 41: 350-2
113. Ziv E, Eldor A, Kleinman Y, et al. Bile salts facilitate the absorption of heparin from the intestine. Biochem Pharmacol 1983; 32 (5): 773-6
114. Dunn JM, Hollister AS. Oral bioavailability of heparin using a novel delivery system. Cur Therap Res 1995; 56 (8): 739-45
115. Majuru S. Advances in the oral delivery of heparin from solid dosage forms using Emisphere's eligen® oral drug delivery technology. Drug Delivery Technology 2004 Oct; 4 (8): 84-9
116. Malkov D, Wang HZ, Dinh S, et al. Pathway of oral absorption of heparin with sodium N-[8-(2-hydroxybenzoyl)amino] caprylate. Pharm Res 2002 Aug; 19 (8): 1180-4
117. Lang S, Rothen-Rutishauser B, Perriard JC, et al. Permeation and pathways of human calcitonin (hCT) across excised bovine nasal mucosa. Peptides 1998; 19 (3): 599-607
118. Yamamoto A, Iseki T, Ochi-Sugiyama M, et al. Absorption of water-soluble compounds with different molecular weights and [Asu1.7]-eel calcitonin from various mucosal administration sites. J Control Release 2001 Oct; 76 (3): 363-74
119. Illum L, Fisher AN, Jabbal-Gill I, et al. Bioadhesive starch microspheres and absorption enhancing agents act synergistically to enhance the nasal absorption of polypeptides. Int J Pharm 2001 Jul; 222 (1): 109-19
120. Callens C, Pringels E, Remon JP. Influence of multiple nasal administrations of bioadhesive powders on the insulin bioavailability. Int J Pharm 2003 Jan; 250 (2): 415-22
121. Law SL, Huang KJ, Chou HY. Preparation of desmopressin-containing liposomes for intranasal delivery. J Control Release 2001 Feb; 70 (3): 375-82
122. Kazuya A, Tetsumi I, Hirotoshi A, et al. Combined use of 2-hydroxypropyl-β-cyclodextrin and a lipophilic absorption enhancer in nasal delivery of the LHRH agonist buserelin acetate in rats. Int J Pharm 1995 Aug; 123 (1): 103-12
123. Oechslein CR, Fricker G, Kissel T. Nasal delivery of octreotide: absorption enhancement by particulate carrier systems. Int J Pharm 1996 Aug; 139: 25-32
124. Illum L. Nasal drug delivery: possibilities, problems and solutions. J Control Release 2003 Feb; 87: 187-98
125. Ugwoke MI, Verbeke N, Kinget R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J Pharm Pharmacol 2001 Jan; 53 (1): 3-21
126. Laursen T, Grandjean B, Jorgensen JO, et al. Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients: comparison with intravenous and subcutaneous administration. Eur J Endocrinol 1996 Sep; 135 (3): 309-15
127. Illum L. Nasal delivery: the use of animal models to predict performance in man. J Drug Target 1996; 3 (6): 427-42
128. Baudoin C. Side effects of antiglaucomatous drugs on the ocular surface. Curr Opin Ophthalmol 1996; 7: 80-6
129. Arici MK, Arici DS, Topalkara A, et al. Adverse effects of topical antiglaucoma drugs on the ocular surface. Clin Experiment Ophthalmol 2000 Apr; 28 (2): 113-7
130. Ceulemans J, Vermeire A, Adriaens E, et al. Evaluation of a mucoadhesive tablet for ocular use. J Control Release 2001 Dec; 77 (3): 333-44
131. Kawakami S, Nishida K, Mukai T, et al. Controlled release and ocular absorption of tilisolol utilizing ophthalmic insert-incorporated lipophilic prodrugs. J Control Release 2001 Oct; 76 (3): 255-63
132. Lee Y-C, Millard JW, Negvesky GJ, et al. Formulation and in vivo evaluation of ocular insert containing phenylephrine and tropicamide. Int J Pharm 1999; 182 (1): 121-6
133. Saettone MF, Salminen L. Ocular inserts for topical delivery. Adv Drug Deliv Rev 1995; 16 (1): 95-106
134. Gurtler F, Kaltsatos V, Boisramé B, et al. Long-acting soluble bioadhesive ophthalmic drug insert (BODI) containing gentamicin for veterinary use: optimization and clinical investigation. J Control Release 1995; 33 (2): 231-6