Mucosal drug delivery: Membranes, methodologies, and applications

Critical Reviews in Therapeutic Drug Carrier Systems

Volumn 21, Issue 3, 2004, Pages 195-256

  Song, Yifan ^a   Wang, Yiping ^b   Thakur, Rashmi ^b   Meidan, Victor M ^c   Michniak, Bozena ^a  

^a RUTGERS NEW JERSEY MEDICAL SCHOOL   (United States)

^b RUTGERS UNIVERSITY   (United States)

^c UNIVERSITY OF STRATHCLYDE   (United Kingdom)

Author keywords

Absorption; Buccal; Nasal; Ocular; Rectal; Vaginal

Indexed keywords

ADHESIVE AGENT; BILE SALT; CYCLODEXTRIN; FUSIDIC ACID; LIPOSOME; MICROSPHERE; SURFACTANT; DRUG; PHARMACEUTICAL VEHICLES AND ADDITIVES;

DRUG BIOAVAILABILITY; DRUG DELIVERY SYSTEM; DRUG ELIMINATION; FIRST PASS EFFECT; MOUTH MUCOSA; REVIEW; ABSORPTION; ANIMAL; BIOAVAILABILITY; BUCCAL DRUG ADMINISTRATION; CHEMISTRY; DRUG DOSAGE FORM; EYE; HUMAN; INTRANASAL DRUG ADMINISTRATION; INTRAVAGINAL DRUG ADMINISTRATION; IONTOPHORESIS; METABOLISM; METHODOLOGY; MUCOSA; RECTAL DRUG ADMINISTRATION;

ABSORPTION; ADJUVANTS, PHARMACEUTIC; ADMINISTRATION, BUCCAL; ADMINISTRATION, INTRANASAL; ADMINISTRATION, INTRAVAGINAL; ADMINISTRATION, RECTAL; ANIMALS; BIOLOGICAL AVAILABILITY; DOSAGE FORMS; DRUG DELIVERY SYSTEMS; EYE; HUMANS; IONTOPHORESIS; MUCOUS MEMBRANE; PHARMACEUTICAL PREPARATIONS;

EID: 5144234094     PISSN: 07434863     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevTherDrugCarrierSyst.v21.i3.20     Document Type: Review

References (258)

1. Rinpoche R. Tibetan Medicine: Illustrated in Original Texts. Berkeley: University of California Press; 1973.
2. Ghalioungui P. Magic and Medical Science in Ancient Egypt. New York Barnes & Noble; 1963.
3. Law J. Not to be sniffed at. Scrip Mag 2000; May:35-38.
4. Proctor DF. The upper airways. I. Nasal physiology and defense of the lungs. Am Rev Respir Dis 1977; 115(1):97-129.
5. Marom Z, Shelhamer J, Kaliner M. Nasal mucus secretion. Ear Nose Throat J 1984; 63(2):36-37, 41-42, 44.
6. Illum L. Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci 2000; 11(1):1-18.
7. Proctor DF, Andersen IHP. The Nose, Upper Airway Physiology and the Atmospheric Environment. Amsterdam-New York: Elsevier Biomedical Press; 1982.
8. th ed. St. Louis: Mosby; 1998.
9. Su KS, Campanale KM, Gries CL. Nasal drug delivery system of a quaternary ammonium compound: clofilium tosylate. J Pharm Sci 1984; 73(9):1251-1254.
10. Nishimura Y. Embryological study of nasal cavity development in human embryos with reference to congenital nostril atresia. Acta Anat (Basel) 1993; 147(3):140-144.
11. Sayani AP, Chien YW. Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Ther Drug Carrier Syst 1996; 13(1-2):85-184.
12. Brain JD, Proctor DF, Reid LM. Respiratory Defense Mechanisms. New York: Marcel Dekker; 1977.
13. Gumbiner B. Structure, biochemistry, and assembly of epithelial tight junctions. Am J Physiol 1987; 253(6 Pt 1):C749-758.
14. Andersen IB, Lundqvist GR, Proctor DF. Human nasal mucosal function under four controlled humidities. Am Rev Respir Dis 1972; 106(3):438-449.
15. Fry F, Black A. Regional deposition and clearance of particles in the human nose. J Aerosol Sci 1973; 4(2):113-116.
16. Lippmann M. Deposition and clearance of inhaled particles in the human nose. Ann Otol Rhinol Laryngol 1970; 79(3):519-528.
17. Chien YW, Su KSE, Chang S-F. Nasal Systemic Drug Delivery. New York Marcel Dekker; 1989.
18. Hehar SS, Mason JD, Stephen AB, Washington N, Jones NS, Jackson SJ, Bush D. Twenty-four hour ambulatory nasal pH monitoring. Clin Otolaryngol 1999; 24(1): 24-25.
19. Quraishi MS, Jones NS, Mason JD. The nasal delivery of drugs. Clin Otolaryngol 1997; 22(4):289-301.
20. Rathbone MJ, Hadgraft J, Roberts MS. Modified-Release Drug Delivery Technology. New York Marcel Dekker; 2003.
21. Proctor DF, Wagner HN, Jr. Clearance of particles from the human nose. Preliminary report. Arch Environ Health 1965; 11:366-371.
22. Sakakura Y, Ukai K, Majima Y, Murai S, Harada T, Miyoshi Y. Nasal mucociliary clearance under various conditions. Acta Otolaryngol 1983; 96(1-2):167-173.
23. Mason S, Paradiso A, Boucher R. Regulation of transepithelial ion transport and intracellular calcium by extracellular ATP in human normal and cystic fibrosis airway epithelium. Br J Pharmacol 1991; 103(3):1649-1656.
24. Holma B, Lindegren M, Andersen JM. pH effects on ciliomotility and morphology of respiratory mucosa. Arch Environ Health 1977; 32(5):216-226.
25. Rautiainen M, Nuutinen J, Kiukaanniemi H, Collan Y. Ultrastructural changes in human nasal cilia caused by the common cold and recovery of ciliated epithelium. Ann Otol Rhinol Laryngol 1992; 101(12):982-987.
26. Cauna N, Hinderer KH. Fine structure of blood vessels of the human nasal respiratory mucosa. Ann Otol Rhinol Laryngol 1969; 78(4):865-879.
27. Chen Y, Liu YQ, Su T, Ren X, Shi L, Liu D, Gu J, Zhang QY, Ding X. Immunoblot analysis and immunohistochemical characterization of CYP2A expression in human olfactory mucosa. Biochem Pharmacol 2003; 66(7):1245-1251.
28. Gu J, Su T, Chen Y, Zhang QY, Ding X. Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity. Toxicol Appl Pharmacol 2000; 165(2):158-162.
29. Romeo VD, deMeireles J, Sileno AP, Pimplaskar HK, Behl CR. Effects of physicochemical properties and other factors on systemic nasal drug delivery. Adv Drug Deliv Rev 1998; 29(1-2):89-116.
30. Gervasi PG, Longo V, Naldi F, Panattoni G, Ursino F. Xenobiotic- metabolizing enzymes in human respiratory nasal mucosa. Biochem Pharmacol 1991; 41(2): 177-184.
31. Dahl AR, Hadley WM. Nasal cavity enzymes involved in xenobiotic metabolism: effects on the toxicity of inhalants. Crit Rev Toxicol 1991; 21(5):345-372.
32. Jones N. The nose and paranasal sinuses physiology and anatomy. Adv Drug Deliv Rev 2001; 51(1-3):5-19.
33. Khanvilkar K, Donovan MD, Flanagan DR. Drug transfer through mucus. Adv Drug Deliv Rev 2001; 48(2-3):173-193.
34. Arora P, Sharma S, Garg S. Permeability issues in nasal drug delivery. Drug Discov Today 2002; 7(18):967-975.
35. McMartin C, Hutchinson LE, Hyde R, Peters GE. Analysis of structural requirements for the absorption of drugs and macromolecules from the nasal cavity. J Pharm Sci 1987; 76(7):535-540.
36. Rojanasakul Y, Wang LY, Bhat M, Glover DD, Malanga CJ, Ma JK. The transport barrier of epithelia: a comparative study on membrane permeability and charge selectivity in the rabbit. Pharm Res 1992; 9(8):1029-1034.
37. Marttin E, Verhoef JC, Cullander C, Romeijn SG, Nagelkerke JF, Merkus FW. Confocal laser scanning microscopic visualization of the transport of dextrans after nasal administration to rats: effects of absorption enhancers. Pharm Res 1997; 14(5): 631-637.
38. Hussain AA. Intranasal drug delivery. Adv Drug Deliv Rev 1998; 29(1-2):39-49.
39. Gizurarson S. Animal models for intranasal drug delivery studies. A review article. Acta Pharm Nord 1990; 2(2):105-122.
40. Hussain A, Hirai S, Bawarshi R. Nasal absorption of propranolol from different dosage forms by rats and dogs. J Pharm Sci 1980; 69(12):1411-1413.
41. Corbo DC, Huang YC, Chien YW. Nasal delivery of progestational steroids in ovariectomized rabbits: I. Progesterone-comparison of pharmacokinetics with intravenous and oral administration. Int J Pharm 1988; 46(1-2):133-140.
42. Huang CH, Kimura R, Nassar RB, Hussain A. Mechanism of nasal absorption of drugs I: Physicochemical parameters influencing the rate of in situ nasal absorption of drugs in rats. J Pharm Sci 1985; 74(6):608-611.
43. Faraj JA, Hussain AA, Aramaki Y, Iseki K, Kagoshima M, Dittert LW. Mechanism of nasal absorption of drugs. IH: Nasal absorption of leucine enkephalin. J Pharm Sci 1990; 79(8):698-702.
44. Huang Y, Donovan MD. Large molecule and particulate uptake in the nasal cavity: the effect of size on nasal absorption. Adv Drug Deliv Rev 1998; 29(1-2):147-155.
45. Yamamoto A, Iseki T, Ochi-Sugiyama M, Okada N, Fujita T, Muranishi S. Absorption of water-soluble compounds with different molecular weights and. J Control Release 2001; 76(3):363-374.
46. Fisher AN, Brown K, Davis SS, Parr GD, Smith DA. The effect of molecular size on the nasal absorption of water-soluble compounds in the albino rat. J Pharm Pharmacol 1987; 39(5):357-362.
47. Fisher AN, Illum L, Davis SS, Schacht EH. Di-iodo-L-tyrosine-labelled dextrans as molecular size markers of nasal absorption in the rat. J Pharm Pharmacol 1992; 44(7): 550-554.
48. Donovan MD, Flynn GL, Amidon GL. The molecular weight dependence of nasal absorption: the effect of absorption enhancers. Pharm Res 1990; 7(8):808-815.
49. Corbo DC, Liu JC, Chien YW. Drug absorption through mucosal membranes: effect of mucosal route and penetrant hydrophilicity. Pharm Res 1989; 6(10):848-852.
50. Lipworth BJ, Jackson CM. Safety of inhaled and intranasal corticosteroids: lessons for the new millennium. Drug Saf 2000; 23(1):11-33.
51. De Ascentiis A, Bettini R, Caponetti G, Catellani PL, Peracchia MT, Santi P, Colombo P. Delivery of nasal powders of beta-cyclodextrin by insufflation. Pharm Res 1996; 13(5):734-738.
52. Ohwaki T, Ando H, Watanabe S, Miyake Y. Effects of dose, pH, and osmolarity on nasal absorption of secretin in rats. J Pharm Sci 1985; 74(5):550-552.
53. Ohwaki T, Ando H, Kakimoto F, Uesugi K, Watanabe S, Miyake Y, Kayano M. Effects of dose, pH, and osmolarity on nasal absorption of secretin in rats. II: Histological aspects of the nasal mucosa in relation to the absorption variation due to the effects of pH and osmolarity. J Pharm Sci 1987; 76(9):695-698.
54. Morimoto K, Yamaguchi H, Iwakura Y, Morisaka K, Ohashi Y, Nakai Y. Effects of viscous hyaluronate-sodium solutions on the nasal absorption of vasopressin and an analogue. Pharm Res 1991; 8(4):471-474.
55. Meltzer EO, Orgel HA, Bush RK, Haltom JR, Metzger WJ, Moss BA, Mitchell DQ, Ballas ZK, Seltzer JM, et al. Evaluation of symptom relief, nasal airflow, nasal cytology, and acceptability of two formulations of flunisolide nasal spray in patients with perennial allergic rhinitis. Ann Allergy 1990; 64(6):536-540.
56. Hallen H, Graf P. Benzalkonium chloride in nasal decongestive sprays has a long-lasting adverse effect on the nasal mucosa of healthy volunteers. Clin Exp Allergy 1995; 25(5):401-405.
57. Graf P, Hallen H. Effect on the nasal mucosa of long-term treatment with oxymetazoline, benzalkonium chloride, and placebo nasal sprays. Laryngoscope 1996; 106(5 Pt 1):605-609.
58. Graf P. Adverse effects of benzalkonium chloride on the nasal mucosa: allergic rhinitis and rhinitis medicamentosa. Clin Ther 1999; 21(10):1749-1755.
59. Cureoglu S, Akkus M, Osma U, Yaldiz M, Oktay F, Can B, Guven C, Tekin M, Meric F. The effect of benzalkonium chloride on rabbit nasal mucosa in vivo: an electron microscopy study. Eur Arch Otorhinolaryngol 2002; 259(7):362-364.
60. Ennis RD, Borden L, Lee WA. The effects of permeation enhancers on the surface morphology of the rat nasal mucosa: a scanning electron microscopy study. Pharm Res 1990; 7(5):468-475.
61. Daugherty AL, Liggitt HD, McCabe JG, Moore JA, Patton JS. Absorption of recombinant methionyl-human growth hormone (Met-hGH) from rat nasal mucosa. Int J Pharm 1988; 45(3):197-206.
62. Chandler SG, Illum L, Thomas NW. Nasal absorption in the rat. I: A method to demonstrate the histological effects of nasal formulations. Int J Pharm 1991; 70(1-2):19-27.
63. Gizurarson S, Marriott C, Martin GP, Bechgaard E. The influence of insulin and some excipients used in nasal insulin preparations on mucociliary clearance. Int J Pharm 1990; 65(3):243-247.
64. Hermens WA, Hooymans PM, Verhoef JC, Merkus FW. Effects of absorption enhancers on human nasal tissue ciliary movement in vitro. Pharm Res 1990; 7(2): 144-146.
65. Merkus FW, Verhoef JC, Romeijn SG, Schipper NG. Absorption enhancing effect of cyclodextrins on intranasally administered insulin in rats. Pharm Res 1991; 8(5): 588-592.
66. Hermens WA, Deurloo MJ, Romeyn SG, Verhoef JC, Merkus FW. Nasal absorption enhancement of 17 beta-estradiol by dimethyl-beta-cyclodextrin in rabbits and rats. Pharm Res 1990; 7(5):500-503.
67. Park JS, Oh YK, Yoon H, Kim JM, Kim CK. In situ gelling and mucoadhesive polymer vehicles for controlled intranasal delivery of plasmid DNA. J Biomed Mater Res 2002; 59(1):144-151.
68. Chien YW. Transnasal systemic medications: fundamentals, developmental concepts, and biomedical assessments. Amsterdam-New York: Elsevier; 1985.
69. Vidgren MT, Kublik H. Nasal delivery systems and their effect on deposition and absorption. Adv Drug Deliv Rev 1998; 29(1-2):157-177.
70. Ugwoke MI, Verbeke N, Kinget R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J Pharm Pharmacol 2001; 53(1):3-21.
71. Lee VHL. Peptide and Protein Drug Delivery. New York: Marcel Dekker; 1991.
72. Davis SS, Illum L. Absorption enhancers for nasal drug delivery. Clin Pharmacokinet 2003; 42(13):1107-1128.
73. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci 1996; 85(10):1017-1025.
74. Marttin E, Verhoef JC, Spies F, van der Meulen J, Nagelkerke JF, Koerten HK, Merkus FW. The effect of methylated beta-cyclodextrins on the tight junctions of the rat nasal respiratory epithelium: electron microscopic and confocal laser scanning microscopic visualization studies. J Control Release 1999; 57(2):205-213.
75. Marttin E, Verhoef JC, Merkus FW. Efficacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein drugs. J Drug Target 1998; 6(1):17-36.
76. Hermens WA, Belder CW, Merkus JM, Hooymans PM, Verhoef J, Merkus FW. Intranasal estradiol administration to oophorectomized women. Eur J Obstet Gynecol Reprod Biol 1991; 40(1):35-41.
77. Hermens WA, Belder CW, Merkus JM, Hooymans PM, Verhoef J, Merkus FW. Intranasal administration of estradiol in combination with progesterone to oophorectomized women: a pilot study. Eur J Obstet Gynecol Reprod Biol 1992; 43(1): 65-70.
78. Schipper NG, Verhoef JC, De Lannoy LM, Romeijn SG, Brakkee JH, Wiegant VM, Gispen WH, Merkus FW. Nasal administration of an ACTH(4-9) peptide analogue with dimethyl-beta-cyclodextrin as an absorption enhancer: pharmacokinetics and dynamics. Br J Pharmacol 1993; 110(4):1335-1340.
79. Marttin E, Romeijn SG, Verhoef JC, Merkus FW. Nasal absorption of dihydroergotamine from liquid and powder formulations in rabbits. J Pharm Sci 1997; 86(7): 802-807.
80. Schipper NG, Verhoef JC, Romeijn SG, Merkus FW. Methylated beta-cyclodextrins are able to improve the nasal absorption of salmon calcitonin. Calcif Tissue Int 1995; 56(4):280-282.
81. Hilsted J, Madsbad S, Hvidberg A, Rasmussen MH, Krarup T, Ipsen H, Hansen B, Pedersen M, Djurup R, et al. Intranasal insulin therapy: the clinical realities. Diabetologia 1995; 38(6):680-684.
82. Chandler SG, Thomas NW, Illum L. Nasal absorption in the rat. III. Effect of lysophospholipids on insulin absorption and nasal histology. Pharm Res 1994; 11(11): 1623-1630.
83. Aungst BJ, Rogers NJ. Site dependence of absorption-promoting actions of laureth-9, Na salicylate, Na2EDTA, and aprotinin on rectal, nasal, and buccal insulin delivery. Pharm Res 1988; 5(5):305-308.
84. Romeo VD, deMeireles JC, Gries WJ, Xia WJ, Sileno AP, Pimplaskar HK, Behl CR. Optimization of systemic nasal drug delivery with pharmaceutical excipients. Adv Drug Deliv Rev 1998; 29(1-2):117-133.
85. Duchateau GSMJE, Zuidema J, Merkus FWHM. Bile salts and intranasal drug absorption. Int J Pharm 1986; 31(3):193-199.
86. Park GB, Shao Z, Mitra AK. Acyclovir permeation enhancement across intestinal and nasal mucosae by bile salt-acylcarnitine mixed micelles. Pharm Res 1992; 9(10): 1262-1267.
87. Gordon GS, Moses AC, Silver RD, Flier JS, Carey MC. Nasal absorption of insulin: enhancement by hydrophobic bile salts. Proc Natl Acad Sci U S A 1985; 82(21): 7419-7423.
88. Olanoff LS, Titus CR, Shea MS, Gibson RE, Brooks CD. Effect of intranasal histamine on nasal mucosal blood flow and the antidiuretic activity of desmopressin. J Clin Invest 1987; 80(3):890-895.
89. Lee WA, Lu HF-L, Maffuid PW, Botet MT, Baldwin PA, Benkert TA, Klingbeil CK. The synthesis, characterization and biological testing of a novel class of mucosal permeation enhancers. J Control Release 1992; 22(3):223-237.
90. Baldwin PA, Klingbeil CK, Grimm CJ, Longenecker JP. The effect of sodium tauro-24,25-dihydrofusidate on the nasal absorption of human growth hormone in three animal models. Pharm Res 1990; 7(5):547-552.
91. Hosoya K, Kubo H, Akutsu T, Natsume H, Sugibayashi K, Morimoto Y. Effect of sodium taurodihydrofusidate on nasal drug delivery: differences in its concentration and penetrant molecular weight. Arch Pharm Res 1994; 17(2):57-59.
92. Kissel T, Drewe J, Bantle S, Rummelt A, Beglinger C. Tolerability and absorption enhancement of intranasally administered octreotide by sodium taurodihydrofusidate in healthy subjects. Pharm Res 1992; 9(1):52-57.
93. Woodley J. Bioadhesion: new possibilities for drug administration? Clin Pharmacokinet 2001; 40(2):77-84.
94. Illum L. Chitosan and its use as a pharmaceutical excipient. Pharm Res 1998; 15(9): 1326-1331.
95. 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(1):55-65.
96. Illum L, Farraj NF, Davis SS. Chitosan as a novel nasal delivery system for peptide drugs. Pharm Res 1994; 11(8):1186-1189.
97. Dyer AM, Hinchcliffe M, Watts P, Castile J, Jabbal-Gill I, Nankervis R, Smith A, Illum L. Nasal delivery of insulin using novel chitosan based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles. Pharm Res 2002; 19(7):998-1008.
98. Dahlin M, Bergman U, Jansson B, Bjork E, Brittebo E. Transfer of dopamine in the olfactory pathway following nasal administration in mice. Pharm Res 2000; 17(6): 737-742.
99. Merkus P, Guchelaar HJ, Bosch DA, Merkus FW. Direct access of drugs to the human brain after intranasal drug administration? Neurology 2003; 60(10):1669-1671.
100. Chen XQ, Fawcett JR, Rahman YE, Ala TA, Frey IW. Delivery of nerve growth factor to the brain via the olfactory pathway. J Alzheimers Dis 1998; 1(1):35-44.
101. Illum L, Jabbal-Gill I, Hinchcliffe M, Fisher AN, Davis SS. Chitosan as a novel nasal delivery system for vaccines. Adv Drug Deliv Rev 2001; 51(1-3):81-96.
102. Eriksson K, Holmgren J. Recent advances in mucosal vaccines and adjuvants. Curr Opin Immunol 2002; 14(5):666-672.
103. Glezen WP. Cold-adapted, live attenuated influenza vaccine. Expert Rev Vaccines 2004; 3(2):131-139.
104. Johnson JB, Gross JF, Hale E. Effects of sublingual administration of nitroglycerin on pulmonary-artery pressure in patients with failure of the left ventricle. N Engl J Med 1957; 257(23):1114-1117.
105. Wertz PW, Squier CA. Cellular and molecular basis of barrier function in oral epithelium. Crit Rev Ther Drug Carrier Syst 1991; 8(3):237-269.
106. Hackemann M, Grubb C, Hill KR. The ultrastructure of normal squamous epithelium of the human cervix uteri. J Ultrastruct Res 1968; 22(5):443-457.
107. Rathbone MJ. Oral Mucosal Drug Delivery. New York: Marcel Dekker; 1996.
108. Squier CA, Cox P, Wertz PW. Lipid content and water permeability of skin and oral mucosa. J Invest Dermatol 1991; 96(1):123-126.
109. Squier CA, Nanny D. Measurement of blood flow in the oral mucosa and skin of the rhesus monkey using radiolabelled microspheres. Arch Oral Biol 1985; 30(4): 313-318.
110. Evered DF, Vadgama JV. Absorption of amino acids from the human buccal cavity. Biochem Soc Trans 1981; 9:132-133.
111. Evered DF, Hunjen MK. Absorption of glutathione from the gastro-intestinal tract. Biochim Biophys Acta 1985; 815:184-188.
112. Evered DF, Mallett C. Thiamine absorption across human buccal mucosa in vivo. Life Sci 1983; 32(12):1355-1358.
113. Evered DF, Sadoogh-Abasian F, Patel PD. Absorption of nicotinic acid and nicotinamide across human buccal mucosa in vivo. Life Sci 1980; 27:1649-1651.
114. Kurosaki Y, Nishimura H, Terao K, Nakayama T, Kimura T. Existence of specialized absorption mechanism for cefadroxil, an minocephalosporin antibiotic, in human oral cavity. Int J Pharm 1992; 82:165-169.
115. Oyama Y, Yamano H, Ohkuma A, Ogawara K, Higaki K, Kimura T. Carrier-mediated transport systems for glucose in mucosal cells of the human oral cavity. J Pharm Sci 1999; 88(8):830-834.
116. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46(1-3):3-26.
117. Francoeur ML, Golden GM, Potts RO. Oleic acid: its effects on stratum corneum in relation to (trans)dermal drug delivery. Pharm Res 1990; 7(6):621-627.
118. Turunen TM, Urtti A, Paronen P, Audus KL, Rytting JH. Effect of some penetration enhancers on epithelial membrane lipid domains: evidence from fluorescence spectroscopy studies. Pharm Res 1994; 11(2):288-294.
119. Gandhi R, Robinson J. Mechanisms of penetration enhancement for transbuccal delivery of salicylic acid. Int J Pharm 1992; 85(1-3):129-140.
120. Aungst BJ, Rogers NJ, Shefter E. Comparison of nasal, rectal, buccal, sublingual and intramuscular insulin efficacy and the effects of a bile salt absorption promoter. J Pharmacol Exp Ther 1988; 244(1):23-27.
121. Ebert CD, Heiber SJ, Dave SC, Kim SW, Mix D. Mucosal delivery of macromolecules. J Control Release 1994; 28:37-44.
122. Hoogstraate JA, Verhoef JC, Pijpers A, Van Leengoed LAMG, Verheiden JHM, Junginger HE, Bodde HE. In vivo buccal delivery of the peptide drug buserelin with glycodeoxycholate as an absorption enhancer in pigs. Pharm Res 1996; 13:395-401.
123. Wolany GJM, Munzer J, Rummelt A, Merkle HP. Buccal absorption of sandostatin (octreotide) in conscious beagle dogs. Proc Int Symp Control Release Bioact Mater 1990; 17:227-225.
124. Senel S, Hincal AA. Drug permeation enhancement via buccal route: possibilities and limitations. J Control Release 2001; 72(1-3):133-144.
125. Nakada Y, Awata N, Nakamichi C, Sugimoto I. The effect of additives on the oral mucosal absorption of human calcitonin in rats. J Pharmacobiodyn 1988; 11(6): 395-401.
126. Oh CK, Ritschel WA. Absorption characteristics of insulin through the buccal mucosa. Methods Find Exp Clin Pharmacol 1990; 12(4):275-279.
127. Sandri G, Rossi S, Ferrari F, Bonferoni MC, Muzzarelli C, Caramella C. Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur J Pharm Sci 2004; 21(2-3):351-359.
128. Senel S, Kremer MJ, Kas S, Wertz PW, Hincal AA, Squier CA. Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. Biomaterials 2000; 21(20): 2067-2071.
129. Portero A, Remunan-Lopez C, Nielsen HM. The potential of chitosan in enhancing peptide and protein absorption across the TR146 cell culture model-an in vitro model of the buccal epithelium. Pharm Res 2002; 19(2):169-174.
130. Lee J, Choi YW. Enhanced ex vivo buccal transport of propranolol: evaluation of phospholipids as permeation enhancers. Arch Pharm Res 2003; 26(5):421-425.
131. Jacobsen J, Nielsen EB, Brondum-Nielsen K, Christensen ME, Olin HB, Tommerup N, Rassing MR. Filter-grown TR146 cells as an in vitro model of human buccal epithelial permeability. Eur J Oral Sci 1999; 107(2):138-146.
132. Sundqvist K, Kulkarni P, Hybbinette SS, Bertolero F, Liu Y, Grafstrom RC. Serum-free growth and karyotype analyses of cultured normal and tumorous (SqCC/Y1) human buccal epithelial cells. Cancer Commun 1991; 3(10-11):331-340.
133. Beckett AH, Triggs EJ. Buccal absorption of basic drugs and its application as an in vivo model of passive drug transfer through lipid membranes. J Pharm Pharmacol 1967; 19:Suppl:31S-41S.
134. Ritschel WA, Shaaya AN, Tan HS. Disposition of nitroglycerin in the beagle dog after intravenous and buccal administration. Methods Find Exp Clin Pharmacol 1985; 7(6):307-313.
135. Wieriks J. Resorption of alpha-amylase upon buccal application. Arch Int Pharmacodyn Ther 1964; 151:126-135.
136. Mehta M, Kemppainen BW, Stafford RG. In vitro penetration of tritium-labelled water (THO) and [3H]PbTx-3 (a red tide toxin) through monkey buccal mucosa and skin. Toxicol Lett 1991; 55(2):185-194.
137. Squier CA, Hall BK. In-vitro permeability of porcine oral mucosa after epithelial separation, stripping and hydration. Arch Oral Biol 1985; 30(6):485-491.
138. Hussain MA, Aungst BJ, Shefter E. Buccal and oral bioavailability of nalbuphine in rats. J Pharm Sci 1986; 75(2):218-219.
139. Singh BB, McKinney RV, Jr., Schuster GS, Erbland JF, Baker RL. In vivo effects of Sn-1,2-dioctanoylglycerol, TPA and A23187 on hamster cheek pouch epithelium. J Oral Pathol 1988; 17(9-10):517-521.
140. Hao J, Heng PW. Buccal delivery systems. Drug Dev Ind Pharm 2003; 29(8): 821-832.
141. Chandra RK. Excessive intake of zinc impairs immune responses. JAMA 1984; 252(11): 1443-1446.
142. Garland ML, Hagmeyer KO. The role of zinc lozenges in treatment of the common cold. Ann Pharmacother 1998; 32(1):63-69.
143. Codd JE, Deasy PB. Formulation development and in vivo evaluation of a novel bioadhesive lozenge containing a synergistic combination of antifungal agents. Int J Pharm 1998; 173(1-2):13-24.
144. Shiffman S, Dresler CM, Hajek P, Gilburt SJ, Targett DA, Strahs KR. Efficacy of a nicotine lozenge for smoking cessation. Arch Intern Med 2002; 162(11):1267-1276.
145. Coluzzi PH, Schwartzberg L, Conroy JD, Charapata S, Gay M, Busch MA, Chavez J, Ashley J, Lebo D, et al. Breakthrough cancer pain: a randomized trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulfate immediate release (MSIR). Pain 2001; 91(1-2):123-130.
146. Hoogstraate AJ, Wertz PW. Drug delivery via the buccal mucosa. Pharm Sci Technol Today 1998; 1(7):309-316.
147. Clarke A, Brewer F, Johnson ES, Mallard N, Hartig F, Taylor S, Corn TH. A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition. J Neural Transm 2003; 110(11):1241-1255.
148. Rowe RC. By gum-a buccal delivery system. Drug Discov Today 2003; 8(14): 617-618.
149. Rassing MR. Chewing gum as a delivery system. Adv Drug Deliv Rev 1994; 13(1-2): 89-121.
150. Rindum JL, Holmstrup P, Pedersen M, Rassing MR, Stoltze K. Miconazole chewing gum for treatment of chronic oral candidosis. Scand J Dent Res 1993; 101(6):386-390.
151. 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.
152. Peh KK, Wong CF. Polymeric films as vehicle for buccal delivery: swelling, mechanical, and bioadhesive properties. J Pharm Pharm Sci 1999; 2(2):53-61.
153. Nagai T, Konishi R. Buccal/gingival drug delivery systems. J Control Release 1987; 6(1):353-360.
154. Anders R, Merkel HP. Evaluation of laminated muco-adhesive patches for buccal drug delivery. Int J Pharm 1989; 49(3):231-240.
155. Cui Z, Mumper RJ. Buccal transmucosal delivery of calcitonin in rabbits using thin-film composites. Pharm Res 2002; 19(12):1901-1906.
156. Jay S, Fountain W, Cui Z, Mumper RJ. Transmucosal delivery of testosterone in rabbits using novel bi-layer mucoadhesive wax-film composite disks. J Pharm Sci 2002; 91(9):2016-2025.
157. Voorspoels J, Remon JP, Eechaute W, De Sy W. Buccal absorption of testosterone and its esters using a bioadhesive tablet in dogs. Pharm Res 1996; 13(8):1228-1232.
158. Cui Z, Mumper RJ. Bilayer films for mucosal (genetic) immunization via the buccal route in rabbits. Pharm Res 2002; 19(7):947-953.
159. Chun MK, Kwak BT, Choi HK. Preparation of buccal patch composed of carbopol, poloxamer and hydroxypropyl methylcellulose. Arch Pharm Res 2003; 26(11): 973-978.
160. Li C, Bhatt PP, Johnston TP. Transmucosal delivery of oxytocin to rabbits using a mucoadhesive buccal patch. Pharm Dev Technol 1997; 2(3):265-274.
161. Ceschel GC, Maffei P, Sforzini A, Lombardi Borgia S, Yasin A, Ronchi C. In vitro permeation through porcine buccal mucosa of caffeic acid phenetyl ester (CAPE) from a topical mucoadhesive gel containing propolis. Fitoterapia 2002; 73 Suppl 1: S44-52.
162. Ishida M, Machida Y, Nambu N, Nagai T. New mucosal dosage form of insulin. Chem Pharm Bull (Tokyo) 1981; 29(3):810-816.
163. Choi H, Jung J, Yong CS, Rhee C, Lee M, Ran J, Park K, Kim C. Formulation and in vivo evaluation of omeprazole buccal adhesive tablet. J Control Release 2000; 68(3): 405-412.
164. Van Roey J, Haxaire M, Kamya M, Lwanga I, Katabira E. Comparative efficacy of topical therapy with a slow-release mucoadhesive buccal tablet containing miconazole nitrate versus systemic therapy with ketoconazole in HIV-positive patients with oropharyngeal candidiasis. J Acquir Immune Defic Syndr 2004; 35(2):144-150.
165. Ameye D, Voorspoels J, Foreman P, Tsai J, Richardson P, Geresh S, Remon JP. Ex vivo bioadhesion and in vivo testosterone bioavailability study of different bioadhesive formulations based on starch-g-poly(acrylic acid) copolymers and starch/poly(acrylic acid) mixtures. J Control Release 2002; 79(1-3):173-182.
166. Park CR, Munday DL. Development and evaluation of a biphasic buccal adhesive tablet for nicotine replacement therapy. Int J Pharm 2002; 237(1-2):215-226.
167. Eouani C, Piccerelle P, Prinderre P, Bourret E, Joachim J. In-vitro comparative study of buccal mucoadhesive performance of different polymeric films. Eur J Pharm Biopharm 2001; 52(1):45-55.
168. de Vries ME, Bodde HE, Busscher HJ, Junginger HE. Hydrogels for buccal drug delivery: properties relevant for muco-adhesion. J Biomed Mater Res 1988; 22(11): 1023-1032.
169. Martin L, Wilson CG, Koosha F, Uchegbu IF. Sustained buccal delivery of the hydrophobic drug denbufylline using physically cross-linked palmitoyl glycol chitosan hydrogels. Eur J Pharm Biopharm 2003; 55(1):35-45.
170. Rossi S, Sandri G, Ferrari F, Bonferoni MC, Caramella C. Buccal delivery of acyclovir from films based on chitosan and polyacrylic acid. Pharm Dev Technol 2003; 8(2): 199-208.
171. Kitano M, Maitani Y, Takayama K, Nagai T. Buccal absorption through golden hamster cheek pouch in vitro and in vivo of 17β-estradiol from hydrogels containing three types of absorption enhancers. Int J Pharm 1998; 174(1-2):19-28.
172. Vyas SP, Sihorkar V, Dubey PK. Preparation, characterization and in vitro antimicrobial activity of metronidazole bearing lectinized liposomes for intra-periodontal pocket delivery. Pharmazie 2001; 56(7):554-560.
173. Yang TZ, Wang XT, Yan XY, Zhang Q. Phospholipid deformable vesicles for buccal delivery of insulin. Chem Pharm Bull (Tokyo) 2002; 50(6):749-753.
174. Fay MF. Indications and applications for iontophoresis. Todays OR Nurse 1989; 11(4): 10-16.
175. Jacobsen J. Buccal iontophoretic delivery of atenolol. HCl employing a new in vitro three-chamber permeation cell. J Control Release 2001; 70(1-2):83-95.
176. Zhang H, Zhang J, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet 2004; 41(9):661-680.
177. Mishima S, Gasset A, Klyce SD, Jr., Baum JL. Determination of tear volume and tear flow. Invest Ophthalmol 1966; 5(3):264-276.
178. Sorensen T, Jensen FT. Tear flow in normal human eyes. Determination by means of radioisotope and gamma camera. Acta Ophthalmol (Copenh) 1979; 57(4):564-581.
179. Tsubota K. Tear dynamics and dry eye. Prog Retin Eye Res 1998; 17(4):565-596.
180. McClellan KA. Mucosal defense of the outer eye. Surv Ophthalmol 1997; 42(3): 233-246.
181. Pleyer U, Baatz H. Antibacterial protection of the ocular surface. Ophthalmologica 1997; 211 Suppl 1:2-8.
182. Van Haeringen NJ. Clinical biochemistry of tears. Surv Ophthalmol 1981; 26(2): 84-96.
183. Thygesen JE, Bach B, Molhave L, Pedersen OF, Prause JU, Skov P. Tear fluid electrolytes and albumin in persons under environmental stress. Environ Res 1987; 43(1): 60-65.
184. Tapaszto I. Pathophysiology of human tears. Int Ophthalmol Clin 1973; 13(1): 119-147.
185. Lee YC, Simamora P, Pinsuwan S, Yalkowsky SH. Review on the systemic delivery of insulin via the ocular route. Int J Pharm 2002; 233(1-2):1-18.
186. Prausnitz MR, Noonan JS. Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug delivery to the eye. J Pharm Sci 1998; 87(12):1479-1488.
187. Hamalainen KM, Kananen K, Auriola S, Kontturi K, Urtti A. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci 1997; 38(3):627-634.
188. Davies NM. Biopharmaceutical considerations in topical ocular drug delivery. Clin Exp Pharmacol Physiol 2000; 27(7):558-562.
189. Daxer A, Misof K, Grabner B, Ettl A, Fratzl P. Collagen fibrils in the human corneal stroma: structure and aging. Invest Ophthalmol Vis Sci 1998; 39(3):644-648.
190. Maren TH, Jankowska L. Ocular pharmacology of sulfonamides: the cornea as barrier and depot. Curr Eye Res 1985; 4(4):399-408.
191. Schwartzman ML, Masferrer J, Dunn MW, McGiff JC, Abraham NG. Cytochrome P450, drug metabolizing enzymes and arachidonic acid metabolism in bovine ocular tissues. Curr Eye Res 1987; 6(4):623-630.
192. Duvvuri S, Majumdar S, Mitra AK. Drug delivery to the retina: challenges and opportunities. Expert Opin Biol Ther 2003; 3(1):45-56.
193. Mitra AK. Ophthalmic Drug Delivery Systems. New York: Marcel Dekker; 2003.
194. Jarvinen K, Jarvinen T, Urtti A. Ocular absorption following topical delivery. Adv Drug Deliv Rev 1995; 16(1):3-19.
195. Bourlais CL, Acar L, Zia H, Sado PA, Needham T, Leverge R. Ophthalmic drug delivery systems-recent advances. Prog Retin Eye Res 1998; 17(1):33-58.
196. Kawakami S, Nishida K, Mukai T, Yamamura K, Kobayashi K, Sakaeda T, Nakamura J, Nakashima M, Sasaki H. Ocular absorption behavior of palmitoyl tilisolol, an amphiphilic prodrug of tilisolol, for ocular drug delivery. J
197. Sunkara G, Deruiter J, Clark CR, Kompella UB. In-vitro hydrolysis, permeability, and ocular uptake of prodrugs of N-[4-(benzoylamino) phenylsulfonyl]glycine, a novel aldose reductase inhibitor. J Pharm Pharmacol 2000; 52(9):1113-1122.
198. Sasaki H, Yamamura K, Mukai T, Nishida K, Nakamura J, Nakashima M, Ichikawa M. Enhancement of ocular drug penetration. Crit Rev Ther Drug Carrier Syst 1999; 16(1):85-146.
199. Jordan CG. How an increase in the carbon chain length of the ester moiety affects the stability of a homologous series of oxprenolol esters in the presence of biological enzymes. J Pharm Sci 1998; 87(7):880-885.
200. Wang W, Bundgaard H, Buur A, Lee VH. Corneal penetration of 5-fluorouracil and its improvement by prodrug derivatization in the albino rabbit: implication in glaucoma filtration surgery. Curr Eye Res 1991; 10(1):87-97.
201. Narurkar MM, Mitra AK. Prodrugs of 5-iodo-2′-deoxyuridine for enhanced ocular transport. Pharm Res 1989; 6(10):887-891.
202. Robinson JR, Yang X. Absorption Enhancers. New York Marcel Dekker; 1999.
203. Sasaki H, Igarashi Y, Nagano T, Nishida K, Nakamura J. Different effects of absorption promoters on corneal and conjunctival penetration of ophthalmic beta-blockers. Pharm Res 1995; 12(8):1146-1150.
204. Monti D, Chetoni P, Burgalassi S, Najarro M, Saettone MF. Increased corneal hydration induced by potential ocular penetration enhancers: assessment by differential scanning calorimetry (DSC) and by desiccation. Int J Pharm 2002; 232(1-2):139-147.
205. Sasaki H, Yamamura K, Mukai T, Nishida K, Nakamura J, Nakashima M, Ichikawa M. Modification of ocular permeability of peptide drugs by absorption promoters. Biol Pharm Bull 2000; 23(12):1524-1527.
206. Madhu C, Rk PJ, Shackleton MJ, Nguyen TG, Tang-Liu DD. Effect of benzalkonium chloride/EDTA on the ocular bioavailability of ketorolac tromethamine following ocular instillation to normal and de-epithelialized corneas of rabbits. J Pharm Sci 1996; 85(4):415-418.
207. Sasaki H, Yamamura K, Tei C, Nishida K, Nakamura J. Ocular permeability of FITC-dextran with absorption promoter for ocular delivery of peptide drug. J Drug Target 1995; 3(2):129-135.
208. Rapoport SI. Osmotic opening of blood-brain and blood-ocular barriers. Exp Eye Res 1977; 25 Suppl:499-509.
209. Xu Y, Chen Z, Song J, Jin W, Li J. [Azone-induced changes on corneal endothelium in rabbits.] Zhonghua Yan Ke Za Zhi 1998; 34(1):25-27.
210. Tang-Liu DD, Richman JB, Weinkam RJ, Takruri H. Effects of four penetration enhancers on corneal permeability of drugs in vitro. J Pharm Sci 1994; 83(1): 85-90.
211. Durand-Cavagna G, Duprat P, Molon-Noblot S, Delort P, Rozier A. Corneal endothelial changes with azone, a penetration enhancer. Lens Eye Toxic Res 1989; 6(1-2):109-117.
212. Tang-Liu DD, Burke PJ. The effect of azone on ocular levobunolol absorption: calculating the area under the curve and its standard error using tissue sampling compartments. Pharm Res 1988; 5(4):238-241.
213. Newton C, Gebhardt BM, Kaufman HE. Topically applied cyclosporine in azone prolongs corneal allograft survival. Invest Ophthalmol Vis Sci 1988; 29(2):208-215.
214. Freedman KA, Klein JW, Crosson CE. Beta-cyclodextrins enhance bioavailability of pilocarpine. Curr Eye Res 1993; 12(7):641-647.
215. Furrer P, Mayer JM, Plazonnet B, Gurny R. Ocular tolerance of absorption enhancers in ophthalmic preparations. AAPS PharmSci 2002; 4(1):E2.
216. Rojanasakul Y, Liaw J, Robinson JR. Mechanisms of action of some penetration enhancers in the cornea: laser scanning confocal microscopic and electrophysiology studies. Int J Pharm 1990; 66(1-3):131-142.
217. Willoughby CE, Batterbury M, Kaye SB. Collagen corneal shields. Surv Ophthalmol 2002; 47(2):174-182.
218. Panchagnula R, Pillai O, Nair VB, Ramarao P. Transdermal iontophoresis revisited. Curr Opin Chem Biol 2000; 4(4):468-473.
219. Rootman DS, Hill JM, Haruta Y, Reidy JJ, Kaufman HE. Trifluridine decreases ocular HSV-1 recovery but not herpetic lesions after timolol iontophoresis. Invest Ophthalmol Vis Sci 1989; 30(4):678-683.
220. Monti D, Saccomani L, Chetoni P, Burgalassi S, Saettone MF. Effect of iontophoresis on transcorneal permeation "in vitro" of two beta-blocking agents, and on corneal hydration. Int J Pharm 2003; 250(2):423-429.
221. Behar-Cohen FF, El Aouni A, Gautier S, David G, Davis J, Chapon P, Parel JM. Trans-scleral Coulomb-controlled iontophoresis of methylprednisolone into the rabbit eye: influence of duration of treatment, current intensity and drug concentration on ocular tissue and fluid levels. Exp Eye Res 2002; 74(1):51-59.
222. Berdugo M, Valamanesh F, Andrieu C, Klein C, Benezra D, Courtois Y, Behar-Cohen F. Delivery of antisense oligonucleotide to the cornea by iontophoresis. Antisense Nucleic Acid Drug Dev 2003; 13(2):107-114.
223. Church AL, Barza M, Baum J. An improved apparatus for trans-scleral iontophoresis of gentamicin. Invest Ophthalmol Vis Sci 1992; 33(13):3543-3545.
224. Sisler HA. Iontophoretic local anesthesia for conjunctival surgery. Ann Ophthalmol 1978; 10(5):597-598.
225. Vollmer DL, Szlek MA, Kolb K, Lloyd LB, Parkinson TM. In vivo trans-scleral iontophoresis of amikacin to rabbit eyes. J Ocul Pharmacol Ther 2002; 18(6):549-558.
226. Parkinson TM, Ferguson E, Febbraro S, Bakhtyari A, King M, Mundasad M. Tolerance of ocular iontophoresis in healthy volunteers. J Ocul Pharmacol Ther 2003; 19(2): 145-151.
227. Felt O, Furrer P, Mayer JM, Plazonnet B, Buri P, Gurny R. Topical use of chitosan in ophthalmology: tolerance assessment and evaluation of precorneal retention. Int J Pharm 1999; 180(2):185-193.
228. Nagarsenker MS, Londhe VY, Nadkarni GD. Preparation and evaluation of liposomal formulations of tropicamide for ocular delivery. Int J Pharm 1999; 190(1):63-71.
229. Zimmer A, Kreuter J, Robinson JR. Studies on the transport pathway of PBCA nanoparticles in ocular tissues. J Microencapsul 1991; 8(4):497-504.
230. Zimmer A, Mutschler E, Lambrecht G, Mayer D, Kreuter J. Pharmacokinetic and pharmacodynamic aspects of an ophthalmic pilocarpine nanoparticle-delivery- system. Pharm Res 1994; 11(10):1435-1442.
231. Stratford RE, Jr., Carson LW, Dodda-Kashi S, Lee VH. Systemic absorption of ocularly administered enkephalinamide and inulin in the albino rabbit: extent, pathways, and vehicle effects. J Pharm Sci 1988; 77(10):838-842.
232. Li BH, Chiou GC. Systemic administration of calcitonin through ocular route. Life Sci 1992; 50(5):349-354.
233. Paavonen J. Physiology and ecology of the vagina. Scand J Infect Dis Suppl 1983; 40: 31-35.
234. Woolfson AD, Malcolm RK, Gallagher R. Drug delivery by the intravaginal route. Crit Rev Ther Drug Carrier Syst 2000; 17(5):509-555.
235. Silberstein SD, Merriam GR. Physiology of the menstrual cycle. Cephalalgia 2000; 20(3):148-154.
236. Owen JA, Jr. Physiology of the menstrual cycle. Am J Clin Nutr 1975; 28(4):333-338.
237. Patton DL, Thwin SS, Meier A, Hooton TM, Stapleton AE, Eschenbach DA. Epithelial cell layer thickness and immune cell populations in the normal human vagina at different stages of the menstrual cycle. Am J Obstet Gynecol 2000; 183(4): 967-973.
238. Washington N, Wilson CG. Physiological Factors Affecting Drug Delivery and Availability. New York: Marcel Dekker; 1995.
239. Hafez ESE. The Human Vagina. Amsterdam: Elsevier/North Holland Biomedical Press; 1978.
240. Richardson JL, Illum L. Routes of delivery-case studies: the vaginal route of peptide and protein drug delivery. Adv Drug Deliv Rev 1992; 8(2):341-366.
241. Hussain N, Jani PU, Florence AT. Enhanced oral uptake of tomato lectin-conjugated nanoparticles in the rat. Pharm Res 1997; 14(5):613-618.
242. Garg S, Anderson RA, Chany CJ 2nd, Waller DP, Diao XH, Vermani K, Zaneveld LJ. Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM). Contraception 2001; 64(1):67-75.
243. Pavelic Z, Skalko-Basnet N, Schubert R. Liposomal gels for vaginal drug delivery. Int J Pharm 2001; 219(1-2):139-149.
244. D'Cruz OJ, Uckun FM. Intravaginal toxicity studies of a gel-microemulsion formulation of spermicidal vanadocenes in rabbits. Toxicol Appl Pharmacol 2001; 170(2): 104-112.
245. Marx PA, Compans RW, Gettie A, Staas JK, Gilley RM, Mulligan MJ, Yamshchikov GV, Chen D, Eldridge JH. Protection against vaginal SIV transmission with microencapsulated vaccine. Science 1993; 260(5112):1323-1327.
246. O'Hagan DT, Rafferty D, Wharton S, Illum L. Intravaginal immunization in sheep using a bioadhesive microsphere antigen delivery system. Vaccine 1993; 11(6): 660-664.
247. Cicinelli E, Cignarelli M, Sabatelli S, Romano F, Schonauer LM, Padovano R, Einer-Jensen N. Plasma concentrations of progesterone are higher in the uterine artery than in the radial artery after vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women. Fertil Steril 1998; 69(3):471-473.
248. van Hoogdalem E, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs. Clin Pharmacokinet 1991; 21(1):11-26.
249. De Boer AG, De Leede LG, Breimer DD. Drug absorption by sublingual and rectal routes. Br J Anaesth 1984; 56(1):69-82.
250. van Hoogdalem EJ, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part II. Clinical applications of peripherally acting drugs, and conclusions. Clin Pharmacokinet 1991; 21(2):110-128.
251. Committee AAoP. Alternative routes of drug administration-advantages and disadvantages (subject review). Pediatrics 1997; 100(1):143-152.
252. Forbes RB, Vandewalker GE. Comparison of two and ten per cent rectal methohexitone for induction of anaesthesia in children. Can J Anaesth 1988; 35(4):345-349.
253. Kawashima S, Nishiura N, Noguchi T, Fujiwara H. Studies on sustained-release suppositories: effect of alginic acid addition on rectal absorption of bacampicillin in rabbits. Chem Pharm Bull (Tokyo) 1989; 37:766-770.
254. Bergogne-Berezin E, Bryskier A. The suppository form of antibiotic administration: pharmacokinetics and clinical application. J Antimicrob Chemother 1999; 43(2): 177-185.
255. van Hoogdalem EJ, Heijligers-Feijen CD, Verhoef JC, de Boer AG, Breimer DD. Absorption enhancement of rectally infused insulin by sodium tauro-24,25-dihydrofusidate (STDHF) in rats. Pharm Res 1990; 7(2):180-183.
256. Matsuda H, Arima H. Cyclodextrins in transdermal and rectal delivery. Adv Drug Deliv Rev 1999; 36(1):81-99.
257. Beebe DS, Belani KG, Chang PN, Hesse PS, Schuh JS, Liao JC, Palahniuk RJ. Effectiveness of preoperative sedation with rectal midazolam, ketamine, or their combination in young children. Anesth Analg 1992; 75(6):880-884.
258. Malinovsky JM, Lejus C, Servin F, Lepage JY, Le Normand Y, Testa S, Cozian A, Pinaud M. Plasma concentrations of midazolam after i.V., nasal or rectal administration in children. Br J Anaesth 1993; 70(6):617-620.