Vagina and uterus as drug-absorbing organs

Enhancement in Drug Delivery

Volumn , Issue , 2006, Pages 396-439

  Malcolm, R Karl ^a   McCullagh, Stephen D ^a   Morrow, Ryan J ^a   Woolfson, A David ^a  

^a QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

Author keywords

[No Author keywords available]

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EID: 85056966344     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (221)

1. Deshpande, A.A., C.T. Rhodes, and M. Danish. 1992. Intravaginal drug delivery. Drug Dev Ind Pharm 18:1225.
2. Tindall, V.R. 1987. Jeffcoate’s principles of gynaecology. London: Butterworths.
3. Jaszczak, S., and E.S.E. Hafez. 1980. The vagina and reproductive processes. In Human reproduction-Conception and contraception, chap. 11. Hagerstown: Harper and Row.
4. Malcolm, R.K., et al. 2004. Vaginal microbicides for the prevention of HIV transmission. In Biotechnology and genetic engineering reviews, chap. 3, 21 vols, ed. S.E. Harding. Andover:Intercept Ltd.
5. Suh, D.D., et al. 2004. MRI of female genital and pelvic organs during sexual arousal. J Psychosom Obstet Gynecol 25:153.
6. Barnhart, K.T., E.S. Pretorius, and D. Malamud. 2004. Lesson learned and dispelled myths:Three-dimensional imaging of the human vagina. Fertil Steril 81:1383.
7. Barnhart, K.T., et al. 2001. Distribution of a spermicide containing nonoxynol-9 in the vaginal canal and the upper female reproductive tract. Hum Reprod 16:1151.
8. Barnhart, K.T., et al. 2001. Distribution of topical medication in the human vagina as imaged by magnetic resonance imaging. Fert Steril 76:189.
9. Zondek, B., and M. Friedmann. 1936. Are there cyclic changes in the human vaginal mucosa? JAMA 106:1051.
10. Patton, D.L., et al. 2000. Epithelial cell layer thickness and immune cell populations in the normal human vagina at different stages of the menstrual cycle. Am J Obstet Gynecol 183:967.
11. Burgos, M.H., and R. de Vargas-Linares. 1978. Ultrastructure of the vaginal mucosa. In The human vagina, eds. E.S.E. Hafez and T.N. Evans, 63-93. Amsterdam: Elsevier/North Holland Biomedical Press.
12. Godley, M.J. 1985. Quantitation of vaginal discharge in healthy volunteers. Br J Obstet Gynecol 92:739.
13. Perl, J.I., G. Milles, and Y. Shimozato. 1959. Vaginal fluid subsequent to panhysterectomy. Am J Obstet Gynecol 78:285.
14. Lissimore, N., and D.W. Currie. 1939. Studies in vaginal fluid. Paper 1. Pathological considerations. Am or Eur J Obstet Gynecol 46:673.
15. Odeblad, E. 1964. Intracavity circulation of aqueous material in the human vagina. Acta Obstet Gynecol Scand 43:360.
16. Lapan, B., and M.M. Friedman. 1950. Glycogen and reducing substances in vaginal mucus:Gestational and cyclical variations. Am J Obstet Gynecol 59:361.
17. Preti, G., G.R. Huggins, and G.D. Silveberg. 1979. Alterations in the organic compounds of vaginal secretions caused by sexual arousal. Fertil Steril 32:47.
18. Wagner, G., and R.J. Levin. 1980. Electrolytes in vaginal fluid during the menstrual cycle of coitally active and inactive women. J Reprod Fert 60:17.
19. Wagner G. 1979. Vaginal transduction. In The biology of the fluids of the female genital tract, eds. F.K. Beller and G.F.B. Shumacher, 25-34. New York: Elsevier/North Holland.
20. Owen, H.O., and D.F. Katz. 1999. A vaginal fluid simulant. Contraception 59:91.
21. Dusitsin, N., et al. 1967. Histidine in human vaginal fluid. Obstet Gynecol 29:125.
22. Croughan, W.S., and Behbehani, A.M. 1988. Comparative study of inactivation of herpes simplex virus types 1 and 2 by commonly used antiseptic agents. J Clin Microb 26:213.
23. Sparling, P.F. 1999. Biology of Neisseria gonorrhoeae. In Sexually transmitted diseases, eds. K.K. Holmes, et al., 433-449. New York: McGraw-Hill.
24. Pettit, R.K., S.C. McAllister, and T.A. Hamer. 1999. Response of gonococcal clinical isolates to acidic conditions. J Med Microbiol 48:149.
25. Graves, S., T. Gotv, and F. Trewartha. 1980. Effect of pH on the motility and virulence of Treponema pallidum (Nichols) and Treponema paraluis cuniculi in vitro under anaerobic conditions. Br J Vener Dis 56:269.
26. Sturn, A.W., and H.C. Zanen. 1984. Characteristics of Haemophilus ducreyi in culture. J Clin Microbiol 19:672.
27. Nagy, E., M. Petterson, and P.-A. Mardh. 1991. Antibiosis between bacteria isolated from the vagina of women with and without signs of bacterial vaginosis. Acta Pathol Microbiol Immunol Scand 99:739.
28. Martin, L.S., J.S. McDougal, and S.L. Loskoski. 1985. Disinfection and inactivation of the human T lymphotropic virus type III/lymphadenopathy-associated virus. J Infect Dis 152:400.
29. Ongradi, J., et al. 1990. Acid sensitivity of cell-free and cell-associated HIV-1: Clinical implications. AIDS Res Human Retrovirol 6:1433.
30. O’Connor, T.J., et al. 1995. The activity of candidate virucidal agents, low pH and genital secretions against HIV-1 in vitro. Int J Sex Trans Dis AIDS 6:267.
31. Wagner, G., and R. Levin. 1984. Human vaginal pH and sexual arousal. Fertil Steril 41:389.
32. Tevi-Benissan, C., et al. 1997. In vivo semen-associated pH neutralization of cervicovaginal secretions. Clin Diagn Lab Immunol 4:367.
33. Masters, W.H., and V.E. Johnson. 1966. Human sexual response. Boston: Little, Brown.
34. Burruano, B.T., R.L. Schnaare, and D. Malamud. 2002. Synthetic cervical mucus formulation. Contraception 66:137.
35. Hillier, S.L., et al. 1993. The normal vaginal flora, H2O2-producing lactobacilli, and bacterial vaginosis in pregnant women. Clin Infect Dis 16 (Suppl. 4):S273.
36. Priestley, C.J.F., B.M. Jones, and L. Goodwin. 1997. What is normal vaginal flora? Genitourin Med 73:23.
37. Fontaine, E.A., E. Claydon, and D. Taylor-Robinson. 1996. Lactobacilli from women with or without bacterial vaginosis and observations on the significance of hydrogen peroxide. Microb Ecol Health Dis 9:135.
38. Valore, E.V., et al. 2002. Antimicrobial components of vaginal fluid. Am J Obstet Gynecol 187:561.
39. Macht, D. 1918. The absorption of drugs and poisons through the vagina. J Pharmacol Pathol 10:509.
40. Hwang, S., et al. 1977. Systems approach to vaginal delivery of drugs IV: Methodology for determination of membrane surface pH. J Pharm Sci 66:778.
41. Ho, N.F.H., et al. 1976. Systems approach to vaginal delivery of drugs III: Simulation studies interfacing steroid release from silicone matrix and vaginal absorption in rabbits. J Pharm Sci 65:1576.
42. Hwang, S., et al. 1976. Systems approach to vaginal delivery of drugs II: In situ vaginal absorption of unbranched aliphatic alcohols. J Pharm Sci 65:1578.
43. Yotsuyanagi, T., et al. 1975. Systems approach to vaginal delivery of drugs I: Development of in situ vaginal drug absorption procedure. J Pharm Sci 64:71.
44. Richardson, J.L., and L. Illum. 1992. Routes of delivery-Case studies. The vaginal route of peptide and protein drug delivery. Adv Drug Deliv Rev 8:341.
45. Sayani, A.P., and Y.W. Chien. 1996. Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Ther Drug Carrier Syst 13:85.
46. Singer, S.J., and G.L. Nicolson. 1972. The fluid mosaic model of the structure of cell membranes. Science 175:720.
47. Chien, Y.W. 1992. Novel drug delivery systems, 2nd ed. New York: Marcel Dekker.
48. De Ziegler D., et al. 1992. Effects of luteal estradiol on the secretory transformation of human endometrium and plasma gonadotropins. J Clin Endocrinol Metab 74:322.
49. Miles, R.A., et al. 1994. Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: A comparative study. Fertil Steril 62:485.
50. Kullander, S., and L. Svanberg. 1985. On resorption and the effects of vaginally administered terbutaline in women with premature labour. Acta Obstet Hynaecol Scand 64:613.
51. Mizutani, T., et al. 1995. Danazol concentrations in ovary, uterus, and serum and their effect on the hypothalamic-pituitary-ovarian axis during vaginal administration of danazol suppository. Fertil Steril 63:1184.
52. Cicinelli, E., and de Ziegler D. 1999. Transvaginal progesterone: Evidence for a new functional ‘portal system’ flowing from the vagina to the uterus. Human Reprod Update 5:365.
53. Bulletti, C., et al. 1997. Targeted drug delivery in gynaecology: The first uterine pass effect. Hum Reprod 12:1073.
54. Kunz, G., et al. 1996. The dynamics of rapid sperm transport through the female genital tract:Evidence from vaginal sonography of uterine peristalsis and hysterosalpingscintigraphy. Hum Reprod 11:629.
55. Kunz, G., et al. 1998. Sonographic evidence for the involvement of the utero-ovarian countercurrent system in the ovarian control of directed uterine sperm transport. Hum Reprod Update 4:667.
56. Wildt, L., et al. 1998. Sperm transport in the female genital tract and its modulation by oxytocin as assessed by hypersalpingoscintigraphy, hysterotonography, electrohysterography and Doppler sonography. Hum Reprod Update 4:655.
57. Einer-Jensen, N. 1992. Counter-current transfer between blood vessels in the ovarian adnex. Acta Obstet Gynecol Scand 71:566.
58. Einer-Jensen, N. 1993. Rapid adsorption and local redistribution after vaginal application in gilts. Acta Vet Scand 34:1.
59. Einer-Jensen, N., et al. 2002. Uterine first pass effect in postmenopausal women. Hum Reprod 17:3060.
60. Cicinelli, E., et al. 2000. Mechanisms of uterine specificity of vaginal progesterone. Hum Reprod 15:159.
61. Cicinelli, E., et al. 2004. “First uterine pass effect” is observed when estradiol is placed in the upper but not the lower third of the vagina. Fertil Steril 81:1414.
62. Lim, J.M.H., E.B.S. Soh, and S. Raman. 1995. Intravaginal misoprostol for termination of midtrimester pregnancy. Aust NZ J Obstet Gynaecol 35:54.
63. Digenis, G.A., et al. 1999. Novel vaginal controlled-delivery systems incorporating coprecipitates of nonoxynol-9. Pharmaceut Develop Tech 4:421.
64. Stein, G.E., and N. Mummaw. 1993. Placebo-controlled trial of itraconazole for treatment of acute vaginal candidiasis. Antimicrob Agents Chemother 37:89.
65. Ostrop, N.J., J. Lamb, and G. Reid. 1998. Intravaginal morphine: An alternative route of administration. Pharmacotherapy 18:863.
66. Enzelsberger, H., et al. 1991. Effects of intravaginal application of estriol tablets in women with urge incontinence. Geburtshilfe und Frauenheilkunde 51:834.
67. Rock, J., R.H. Barker, and W.B. Bacon. 1947. Vaginal absorption of penicillin. Science 105:13.
68. Yamashita, A., S. Oshima, K. Matsuo, K. Ito, A. Ito, and Y. Mori. 1991. Pharmacological studies of intravaginally applied dehydroepiandrosterone sulfate. Folia Pharmacologica Japonica 98:31.
69. Tan, L.K., and S.K. Tay. 1999. Two dosing regimens for preinduction cervical priming with intravaginal dinoprostone pessary: A randomised clinical trial, Br J Obstet Gynaecol 106:907.
70. Abrams, L.S., and H.S. Weintraub. 1983. Disposition of radioactivity following intravaginal administration of 3H-miconazole nitrate. Am J Obstet Gynecol 147:970.
71. Daneshmend, T.K. 1986. Systemic absorption of miconazole from the vagina. J Antimicrob Chemother 18:507.
72. Borgida, A.F., J.F. Rodis, W. Hanlon, A. Craffey, L. Ciarleglio, and W.A. Campbell. 1995. Second trimester abortion by intramuscular 15-methyl-prostaglandin F2-alpha or intravaginal prostaglandin E(2) suppositories-A randomized trial. Obstet Gynecol 85:697.
73. Mircioiu, C., et al. 1998. Pharmacokinetics of progesterone in postmenopausal women: 1. Pharmacokinetics following intravaginal administration. Eur J Drug Metabol Pharmacokin 23:391.
74. Junginger, H.E. 1991. Mucoadhesive hydrogels. Pharmazeutische Industrie 53:1056.
75. Brannonpeppas, L. 1993. Novel vaginal drug-release applications. Adv Drug Deliv Rev 11:169.
76. Lehr, C.M., et al. 1992. A surface energy analysis of mucoadhesion: Contact angle measurements on polycarbophil and pig intestinal mucosa in physiologically relevant fluids. Pharm Res 9:70.
77. Coury, A.J., et al. 1984. Recent developments in hydrophilic polymers. Med Dev Dia Ind 6:28.
78. Woolfson, A.D., R.K. Malcolm, and R. Gallagher. 2000. Drug delivery by the intravaginal route. Crit Rev Ther Drug Carrier Syst 17:509.
79. Malcolm, R.K. 2003. The intravaginal ring. In Modified-release drug delivery technology, eds. M.J. Rathbone, J. Hadgraft, and M.S. Roberts. New York: Marcel Dekker, chap. 64.
80. World Health Organization (WHO). 2002. The IUD-worth singing about. WHO Progress in Reproductive Health Research 60:1. Available at: www.who.int /reproductive-health /hrp /progress /60/Progress60.pdf
81. Johns Hopkins Center for Communication Programs, Population Information Program. IUDs. Population Reports, 23, 1995. Available at: www.jhuccp.org /pr/b6edsum.stm.
82. Luukkainen, T., and J. Toivonen. 1995. Levonorgestrel-releasing IUD as a method of contraception with therapeutic properties. Contraception 52:269.
83. Kishen, M. 1998. Gynefix. IPPF Medical Bulletin, 32.
84. Van Os, W., and D. Edelman. 1998. New Directions in IUD. Dev Adv Contracept 14:41.
85. Wildemeersch, D., et al. 1999. GyneFIX. The frameless intrauterine contraceptive implant-An update for interval, emergency and postabortal contraception. Br J Fam Plan 24.
86. Corbellis, L., et al. 2004. A danazol-loaded intrauterine device decreases dysmenorrheal, pelvic pain, and dyspareunia associated with endometriosis. Fertil Steril 82:239.
87. Tamaoka, Y., et al. 2004. Treatment of endometrial hyperplasia with a danazol-releasing intrauterine device: A prospective study. Gynecol Obstet Invest 58:42.
88. UNAIDS (2002). Report on the global HIV/AIDS epidemic, July 2002. Joint United Nations Programme on HIV /AIDS, Geneva. Available at http://www.unaids.org /html /pub/Global-Reports /Barcelona/BRGlobal_AIDS_Report_en_pdf.pdf.
89. Gerbase, A.C., et al. 1998. Global prevalence and incidence estimates of selected curable STDs. Sex Trans Infect Suppl 1:S12.
90. Fauci A.S. 1999. The AIDS epidemic. N Engl J Med 341:1046.
91. Wasserheit, N.J. 1992. Epidemiological synergy: Interrelationships between HIV and infection and other STDs. Sex Trans Dis 19:61.
92. Stratton P., and N.J. Alexander. 1993. Prevention of sexually transmitted infections: Physical and chemical barrier methods. Infect Dis Clin North Am 7:841.
93. Van de Wijgert, J., and C. Coogins. 2002. Microbicides to prevent heterosexual transmission of HIV:T en years down the road. AIDScience 2: 1. Available a t: www.aidscience.org /Articles /aidscience015.asp
94. Avert-A guide to HIV and AIDS treatment. Available at: www.avert.org
95. amfAR Aids Research-Microbicides: A New Weapon Against HIV. Available at: www.amfar.org
96. AIDS Action-Policy Facts. Microbicides. March 2002. Available at: www.thebody. com /aac/brochures /microbicides.html.
97. Knodel, J., and M. VanLandingham. 1996. Thai views of sexuality and sexual behaviour. Health Trans Rev 6:179.
98. The Terrence Higgins Trust. Briefing on Microbicides: Prevention for Women. Available at:www.iapac.org /clinmgt /women/microb.html.
99. AIDS Epidemic Update 2004, Joint United Nations Programme of HIV /AIDS, Available at:www.unaids.org /wad2004/report.html.
100. Royce, R.A., A. Sena, W. Cates, Jr., and M.S. Cohen. 1997. Sexual transmission of HIV. N Engl J Med 336:1072.
101. AIDS Epidemic update (2002). UNAIDS/WHO, December 2002. Available at: www.who.int /hiv/pub/epidemiology /epi2002/en /.
102. Stone, A. 2002. Microbicides: A new approach to preventing HIV and other sexually transmitted infections. Nat Rev Drug Discov 1:997.
103. Singh, B., J.C. Cutler, and H.M.D. Utidjian. 1972. Studies of the development of a vaginal preparation providing both prophylaxis against venereal disease and other genital infections and contraception: II. Effect in vitro of vaginal contraception and non-contraceptive preparations on Treponema pallidum and Neisseria gonorrhoeae. Br J Ven Dis 48:57.
104. Hicks, D., L. Martin, and J. Getchell. 1985. Inactivation of HTLV-III/LAV-infected cultures of normal human lymphocytes by nonoxynol-9 in vitro. Lancet 2:1422.
105. Judson. F.N., et al. 1989. In vitro evaluation of condoms with and without nonoxynol-9 as physical and chemical barriers against Chlamydia trachomatis, herpes simplex virus type 2, and human immunodeficiency virus. Sex Trans Dis 16:51.
106. Van Damme, L., et al. 2002. Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: A randomised controlled trial. Lancet 360:971.
107. Kreiss J., et al. 1992. Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA 268:477.
108. Roddy, R.E., et al. 1998. A controlled trial of nonoxynol-9 film to reduce male-to-female transmission of sexually transmitted diseases. N Engl J Med 339:504.
109. Isaacs, C.E., R.E. Litov, and H. Thormar. 1995. Antimicrobial activity of lipids added to human milk, infant formula, and bovine milk. Nutr Biochem 6:362.
110. Kabara, J.J. 1978. Fatty acids and derivatives as antimicrobial agents. In The pharmacological effect of lipids, ed. J.J. Kabara, 1-14. St. Louis: American Oil Chemists Society.
111. Shibasaki, I., and N. Kato. 1978. Combined effects on antibacterial activity of fatty acids and their esters against gram-negative bacteria. In The pharmacological effects of lipids, ed. J.J. Kabara, 15-24. St. Louis: American Oil Chemists Society.
112. Thormar H., C.E. Isaacs, H.R. Brown, M.R. Barshatzky, and T. Pessolano. 1987. Inactivation of enveloped viruses and killing of cells by fatty acids and monoglycerides. Antimicrob Agents Chemother 31:27.
113. Welsh, J.K., M. Arsenakis, R.J. Coelen, and J.T. May. 1979. Effect of antiviral lipids, heat, and freezing on the activity of viruses in human milk. J Infect Dis 140:322.
114. Thormar, et al. 1999. Hydrogels containing monocaprin have potent microbicidal activities against sexually transmitted viruses and bacteria in vitro. Sex Trans Infect 75:181.
115. Lampe, M.F., et al. 1998. Killing of Chlamydia trachomatis by novel antimicrobial lipids adapted from compounds in human breast milk. Antimicrob Agents Chemother 42:1239.
116. Fienberg, M.B., and J.P. Moore. 2002. AIDS vaccine models: Challenging challenge viruses. Nat Med 8:207.
117. Microbicide Research and Development-Progress Report. January 2002. Alliance for Microbicide Development.
118. Esser, M.T., et al. 1999. Cyanovirin-N binds to gp120 to interfere with CD4-dependent human immunodeficiency virus type 1 virion binding, fusion, and infectivity but does not affect the CD4 binding site on gp120 or soluble CD4- induced conformational changes in gp120. J Virol 73:4360.
119. O’Keefe, B.R., et al. 2000. Analysis of the interaction between the HIV-inactivating protein cyanovirin-N and soluble forms of the envelope glycoproteins gp120 and gp41. Mol Pharmacol 58:982.
120. Bolmstedt, A.J., et al. 2001. Cyanovirin-N defines a new class of antiviral agent targeting N-linked, high-mannose glycans in an oligosaccharide-specific manner. Mol Pharmacol 59:949.
121. Cariati, S. 2002. Invisible condoms for women on the way, Society for Womens Health Research. Available at: http://www.womens-health.org /press /newsservice /011702.htm.
122. Parr, M.B., and E.L. Parr. 1985. Immunohistochemical localization of immunoglobins A, G and M in female genital tract. J Reprod Fert 74:361.
123. Forrest, B.D. 1991. Women, HIV, and mucosal immunity. Lancet 337:835.
124. Kozlowski, P.A., et al. 2002. Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: Influence of the menstrual cycle. J Immunol 169:566.
125. Upadhyay, S. 1995. Reproductive tract immunity for the control of fertility: New strategies for immunocontraception. Mucos Immun Update 3:7.
126. Alexander, N.J., D.L. Fulgham, and E. Goldberg, E. 1992. Contraceptive vaccine development:Secretory immune response in mice and monkeys. Vaccine Res 1:331.
127. Mestecky, J., et al. 1997. Current options for vaccine delivery systems by mucosal routes. J Control Release 48:243.
128. Russel, M.W. 2002. Immunization for protection of the reproductive tract: A review. Am J Reprod Immunol 47:265.
129. O’Hagan, D.T. 1998. Microparticles and polymers for the mucosal delivery of vaccines. Adv Drug Deliv Rev 34:305.
130. Parr, E.L., M.B. Parr, and M. Thapar. 1988. A comparison of specific antibody responses in mouse vaginal fluid after immunization by various routes. J Reprod Immunol 14:165.
131. Russell, M.W., and J. Mestecky. 1998. Humoral immune responses to microbial infections in the genital tract. Microb Infect 34:305.
132. Parr, M.B., and E.L. Parr. 1994. Mucosal immunity in the female and male reproductive tracts. In Handbook of mucosal immunology, eds. P.L. Ogra, W. Strober, J. Mestecky, J.R. McGhee, M.E. Lamm, and J. Bienenstock, 667. San Diego: Academic Press.
133. Bernkop-Schnurch, A., and M. Hornof. 2003. Intravaginal drug delivery systems. Am J Drug Deliv 1:241.
134. Whalen, R.G. 1996. DNA vaccines for emerging infectious diseases: What if ? Emerg Infect Dis 2:168.
135. Kozwolski, P.A., M.R. Neutra, T.P. Flanigan, and S. Cu-Uvin. 2000. Induction of antibodies in women after vaginal immunization during the mid-proliferative or mid-secretory phase of the menstrual cycle. FASEB J 14:A1248.
136. Gillgrass, A.E., A.A. Ashkar, K.L. Rosenthal, and C. Kaushic. 2003. Prolonged exposure to progesterone prevents induction of protective mucosal responses following intravaginal immunization with attenuated herpes simplex virus type 2. J Virol 77:9845.
137. Kaushic, C., A.A. Ashkar, L.A. Reid, and K.L. Rosenthal. 2003. Progesterone increases susceptibility and decreases immune responses to genital herpes infection. J Virol 77:4558.
138. Li Wan Po, A., E. Rogers, M. Shepphard, and E.M. Scott. 1995. Delivery systems for nonparenteral vaccines. Adv Drug Deliv Rev 18:101.
139. Kozlowski, P.A., et al. 1999. Mucosal vaccination strategies for women. J Inf Dis 179:S493.
140. Medaglini, D., et al. 1997. Commensal bacteria as vectors for mucosal vaccines against sexually transmitted diseases: Vaginal colonization with recombinant streptococci induces local and systemic antibodies in mice. Vaccine 15:1330.
141. Schreckenberger, C., et al. 2001. Induction of an HPV 6bL1-specific mucosal IgA response by DNA immunization. Vaccine 19:227.
142. Chattergoon, M., J. Boyer, and D.B. Weiner. 1997. Genetic immunization: A new era in vaccines and immune therapeutics. FASEB J 11:753.
143. Bernstein, D.I. 2000. Effect of route of vaccination with vaccinia virus expressing HSV-2 glycoprotein D on protection from genital HSV-2 infection. Vaccine 18:1351.
144. McLean, C.S., D. NiChallanain, I. Duncan, M.E.G. Boursnell, R. Jennings, and S.C. Inglis. 1996. Induction of a protective immune response by mucosal vaccination with a DISC HSV-1 vaccine. Vaccine 14:987.
145. Parr, E.L., and M.B. Parr. 1999. Immune responses and protection against vaginal infection after nasal or vaginal immunization with attenuated herpes simplex type-2. Immunology 98:639.
146. Ogra, P.L., and S.S. Ogra. 1973. Local antibody response to poliovaccine in the human female genital tract. J Immun 110:1307.
147. Cardenas-Freytag, L., et al. 2002. Partial protection against experimental vaginal candidiasis after mucosal vaccination with heat-killed Candida albicans and the mucosal adjuvant LT(R192G). Med Mycol 40:291.
148. Uehling, D.T., et al. 2003. Phase 2 clinical trial of a vaginal mucosal vaccine for urinary tract infections. J Urol 170:867.
149. Dumais, N., et al. 2002. Mucosal immunization with inactivated human immunodeficiency virus plus CpG oligodeoxynucleotides induces genital immune responses and protection against intravaginal challenge. J Infect Dis 15:1098.
150. Pyles, R.B., D. Higgins, C. Chalk, A. Zalar, J. Eiden, C. Brown, G. VanNest, and L.R. Stanberry. Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection. J Virol 76:11387.
151. OHagan, D.T., D. Rafferty, S. Wharton, and L. Illum. 1993. Intravaginal immunization in sheep using a bioadhesive microsphere antigen delivery system. Vaccine 11:660.
152. Wassen, L., K. Schon, J. Holmgren, M. Jertborn, and N. Lycke. 1996. Local intravaginal vaccination of the female genital tract. Scand J Immunol 44:408.
153. Johansson, E.L., L. Wassen, J. Holmgren, M. Jertborn, and A. Rudin. 2001. Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans. Infect Immun 69:7481.
154. Moreno, L., and N. Goldman. 1991. Contraceptive failure rates in developing countries: Evidence from the demographic and health surveys. Int Fam Plan Perspect 17:44.
155. Jones, E.F., and J.D. Forrest. 1992. Contraceptive failure rates based on the 1988 NSFG. Fam Plan Perspect 24:12.
156. Croxatto, H.B., et al. 1982. Plasma progesterone levels following subdermal implantation of progesterone pellets in lactating women. Acta Endocrinol 100:630.
157. Croxatta, H.B., et al. 1982. Fertility regulation in nursing women. II. Comparative performance of progesterone implants versus placebo and copper T. Am J Obstet Gynecol 144:201.
158. Diaz, S., et al. 1984. Fertility regulation in nursing women. VI. Contraceptive effectiveness of a subdermal progesterone implant. Contraception 30:311.
159. Duncan, G.W. 1970. Medicated devices and methods. US Patent 3,545,439.
160. Massai, R., et al. 1999. Pre-registration study on the safety and contraceptive efficacy of a progesterone-releasing vaginal ring on Chilean nursing women. Contraception 60:9.
161. Massai, R., et al. 2000. Vaginal rings for contraception in lactating women. Steroids 65:703.
162. Diaz, S., et al. 1985. Fertility regulation in nursing women. VIII. Progesterone plasma levels and contraceptive efficacy of a progesterone-releasing vaginal ring. Contraception 32:603.
163. Shaaban, N.N. 1991. Contraception with progestogens and progesterone during lactation. J Steroid Biochem Molec Biol 40:705.
164. Croxatto, H.B., and S. Diaz, S. 1991. Progesterone vaginal rings for contraception during breastfeeding. In Female contraception and male fertility regulation, vol. 2, eds. B. Runnebaum, T. Rabe, and L. Kiessel, 135-142. New Jersey: The Parthenon Publishing Group.
165. Sivin, I., et al. 1997. Contraceptives for lactating women: A comparative trial of a progesteronereleasing vaginal ring and the copper T 380A IUD. Contraception 55:225.
166. Diaz, S., et al. 1997. Fertility regulation in nursing women. IX. Contraceptive performance, duration of lactation, infant growth, and bleeding patterns during use of progesterone vaginal rings, progestin-only pills, Norplant1 implants and copper T 380-A intrauterine devices. Contraception 56:223.
167. Chen, J.H., et al. 1998. The comparative trial of TCu 380A IUD and progesterone-only vaginal ring used by lactating women. Contraception 57:371.
168. Massai, R., et al. 2000. Vaginal rings for contraception in lactating women. Steroids 65:703.
169. Sitruk-Ware, R., et al. 2003. Nestorone1: Clinical implications for contraception and HRT. Steroids 68:907.
170. Kumar, N., et al. 2000. Nesterone1: A progestin with a unique pharmacological profile. Steroids 65:629.
171. Shapiro, E.L., et al. 1962. 16-Alkylated progestogens. J Med Pharm Chem 5:975.
172. Bottela, J., et al. 1986. Interaction of new 19-norprogesterone derivative with progestagen, mineralocortoid and glucocorticoid receptors. J Pharmacol 17:699.
173. Killick, S. 2002. Complete and robust ovulation inhibition with NuvaRing. Eur J Contracept Reprod Health Care 7:13.
174. Veres, S., L. Miller, and B. Burington. 2004. A comparison between the vaginal ring and oral contraceptives. Obstet Gynecol 104:555.
175. Oddson, K., et al. 2005. Superior cycle control with a contraceptive vaginal ring compared with an oral contraceptive containing 30 mu g ethinylestradiol and 150 mug levonorgestrel: A randomized trial. Hum Reprod 20:557.
176. Vree, M. 2002. Lower hormone dosage with improved cycle control. Eur J Contracept Reprod Health Care 7:25.
177. Dieben, T.O.M., F.J.M.E., Roumen, and D. Apter. 2002. Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol 100:585.
178. Szarewski, A. 2002. High acceptability and satisfaction with NuvaRing use. Eur J Contracept Reprod Health Care 7:31.
179. Novak, A., et al. 2003. The combined contraceptive vaginal ring, NuvaRing: An international study of user acceptability. Contraception 67:187.
180. Timmer, C.J., and T.M.T. Mulders. 2000. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokin 39:233.
181. Gabrielsson, J., et al. 1995. New kinetic data on estradiol in light of the vaginal ring concept. Matutitas S35-S39.
182. Bachmann, G. 1995. The estradiol vaginal ring-A study of existing clinical data. Matutitas S21-S39.
183. Wildemeersch, D., et al. 2004. Endometrial safety with a low-dose intrauterine levonorgestrelreleasing system after 3 years of estrogen substitution therapy. Maturitas 48:65.
184. Wildemeersch, D., and E. Schacht. 2001. Treatment of menorrhagia with a novel ‘frameless’ intrauterine levonorgestrel-releasing drug delivery system: A pilot study. Eur J Contracept Reprod Health Care 6:93.
185. Wildemeersch, D., and E. Schacht. 2000. Contraception with a novel ‘frameless’ intrauterine levonorgestrel-releasing drug delivery system: A pilot study. Eur J Contracept Reprod Health Care 5:234.
186. Wildemeersch, D., et al. 2003. Miniature, low-dose, intrauterine drug-delivery systems. Annals NY Acad Sci 997:174.
187. Couture, J.A., and L. Valiquette. 2000. Urinary incontinence. Ann Pharmacother 34:646.
188. Hattori, T. 1998. Drug treatment for urinary incontinence. Drugs Today 34:125.
189. Pietzko, A., et al. 1994. Influences of trospium chloride and oxybutynin on quantitative EEG in healthy-volunteers. Eur J Clin Pharmacol 47:337.
190. Goldenberg, M.M. 1999. An extended-release formulation of oxybutynin chloride for the treatment of overactive urinary bladder. Clin Ther 21:634.
191. Anderson, R.U., et al. 1999. Once daily controlled versus immediate release oxybutynin chloride for urge urinary incontinence. J Urol 161:1809.
192. Gupta, S.K., and G. Sathyan. 1999. Phamacokinetics of an oral once-a-day controlled-release oxybutynin formulation compared with immediate-release oxybutynin. J Clin Pharmacol 39:289.
193. Gupta, S.K., et al. 1999. Quantitative characterisation of therapeutic index: Application of mixedeffects modelling to evaluate oxybutynin dose-efficacy and dose-side effect relationships. Clin Pharmacol Ther 65:672.
194. Lukkari, E., et al. 1998. Cytochrome P450 specificity of metabolism and interaction of oxybutynin in human liver microsomes. Pharmacol Toxicol 82:161.
195. Douchamps, J., et al. 1988. The pharmacokinetics of oxybutynin. Eur J Clin Pharmacol 35:515.
196. Yaich, M., et al. 1998. In vitro cytochrome p450 dependant metabolism of oxybutynin to N-deethyloxybutynin in humans. Pharmacogenetics 8:4.
197. Nilsson, C.G., et al. 1997. Comparison of a 10mg controlled release oxybutynin tablet with a 5 mg oxybutynin tablet in urge continence patients. Neurourol Urodyn 16:533.
198. Castleden, C.M., et al. 1990. Oxybutynin and urinary incontinence. Age Ageing 19:72.
199. Brendler, C.B., et al. 1989. Topical oxybutynin chloride for relaxation of dysfunctional bladders. J Urol 141:1350.
200. Yarker, Y.E., K.L. Goa, and A. Fitton. 1995. Oxybutynin-A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic use in detrusor instability. Drug Ageing 6:243.
201. Birns, J., E, Lukkari, and J.G.A. Malonelee. 2000. Randomised controlled trial comparing the efficacy of controlled-release oxybutynin tablets (10 mg once daily) with conventional oxybutynin tablets (5 mg twice daily) in patients whose symptoms were stabilized on 5 mg twice daily of oxybutynin. BJU Int 85:793.
202. Versi, E., et al. 2000. Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. Obstet Gynecol 95:718.
203. Schroder, A. et al. 2000. Absorption of oxybutynin from vaginal inserts: Drug blood levels and the response of the rabbit bladder. Urology 56:1063.
204. Woolfson, A.D., R.K. Malcolm, and R.J. Gallagher. 2003. Design of a silicone reservoir intravaginal ring for the delivery of oxybutynin. J Control Release 91:465.
205. www.barrlabs.com
206. Manara, A.R., et al. 1989. Pharmacokinetics of morphine following the buccal route. Br J Anaesth 62:498.
207. Bell, M.D.D., et al. 1985. Buccal morphine-A new route for analgesia? Lancet 1:71.
208. Hirsch, J.D. 1984. Sublingual morphine sulfate in chronic pain management. Clin Pharm 3:585.
209. Pannuti, F., et al. 1982. Control of chronic pain in very advanced cancer patients with morphine hydrochloride administered by oral, rectal and sublingual routes. Clinical report and preliminary results on the morphine pharmacokinetics. Pharmacol Res Commun 14:369.
210. Davis, T., et al. 1993. Comparative morphine pharmacokinetics following sublingual, intramuscular and oral administration in patients with cancer. Hospice J 9:85.
211. Daneshmend, T.K., and D.W. Warnock. 1983. Clinical pharmacokinetics of systemic antifungal drugs. Clin Pharmacokin 8:17.
212. Brugmans, J., et al. 1972. Systemic antifungal potential, safety, biotransport and transformation of miconazole nitrate. Eur J Clin Parmacol 5:93.
213. Vukovich, R.A., A. Heald, and A. Darragh. 1977. Vaginal absorption of two imidazole antifungal agents, econazole and miconazole. Clin Pharmacol Therap 21:121.
214. Chamness, G.C., R.H. Asch, and C.J. Pauerstein. 1980. Danazol binding and translocation of steroid receptors. Am J Obstet Gynecol 136:426.
215. Taketani, Y., and M. Mizuno. 1985. Direct action of danazol on endometrial cells in vitro. Sanka to Fujinka (in Japanese) 8:89.
216. Surrey, E.S., and J. Halme. 1992. Direct effects of medroxyprogesterone acetate, danazol, and leuprolide acetate on endometrial stromal cell proliferation in vitro. Fertil Steril 58:273.
217. Braun, D.P., H. Gebel, and W.P. Dmowski. 1994. Effect of danazol in vitro and in vivo on monocyte-mediated enhancement of endometrial cell proliferation in women with endometriosis. Fertil Steril 62:89.
218. Chin, K., et al. In vitro augmentative effect of danazol on apoptosis of endometrial cells. Abstract of 18th Annual Meeting of Japan Endometriosis Society, p. 17, 1997.
219. Igarashi, M., et al. 1998. Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis. Hum Reprod 13:1952.
220. Igarashi, M. 1990. A new therapy for pelvic endometriosis and uterine adenomyosis: Local effect of vaginal and intrauterine danazol application, Asia-Oceania. J Obstet Gynaecol 16:1.
221. Dmowski, W.P., and T.I. Janicki. 2004. Intravaginal danazol is efficacious with limited side-effect profile in the treatment of endometriosis. Obstet Gynecol 103:60S.