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Microbicide Dosage Forms

  • L. C. RohanEmail author
  • B. Devlin
  • H. Yang
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 383)

Abstract

Microbicides are topically applied, user controlled dosage forms that are being developed to prevent the transmission of HIV during coitus. Early candidates focused on coitally dependent dosage forms such as gels and creams. More recent development has focused on broadening the coitally dependent options through the introduction of films and fast dissolving tablets. Additionally, it has become important to have longer acting products to minimize the burden of user compliance and thus vaginal rings have been developed providing sustained delivery of antiretroviral drugs. This chapter discusses the history of microbicides along with a detailed description of coitally dependent products, gels, films, tablets diaphragms, as well as coitally independent dosage forms such as vaginal rings and the introduction of a new technology, electrospun fibers.

Keywords

Dosage Form Vaginal Ring Cellulose Acetate Phthalate Vaginal Tablet Microbicide Candidate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Abdool Karim Q, Abdool Karim SS et al (2010) Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329(5996):1168–1174PubMedCentralPubMedGoogle Scholar
  2. Abdool Karim SS, Richardson BA et al (2011) Safety and effectiveness of BufferGel and 0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS 25(7):957–966PubMedGoogle Scholar
  3. Adriaens E, Remon JP (2008) Mucosal irritation potential of personal lubricants relates to product osmolality as detected by the slug mucosal irritation assay. Sex Transm Dis 35(5):512–516PubMedGoogle Scholar
  4. Agashe H, Hu M et al (2012) Formulation and delivery of microbicides. Curr HIV Res 10(1):88–96PubMedGoogle Scholar
  5. Akil A, Parniak MA et al (2011) Development and characterization of a vaginal film containing dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), for prevention of HIV-1 sexual transmission. Drug Deliv Transl Res 1(3):209–222PubMedCentralPubMedGoogle Scholar
  6. Alexander NJ, Baker E et al (2004) Why consider vaginal drug administration? Fertil Steril 82(1):1–12PubMedGoogle Scholar
  7. Austin GD, Colburn TJ et al (1998) Contraceptive diaphragm. US patent Number 5, 900Google Scholar
  8. Ayres C, Bowlin GL et al (2006) Modulation of anisotropy in electrospun tissue-engineering scaffolds: analysis of fiber alignment by the fast Fourier transform. Biomaterials 27(32):5524–5534PubMedCentralPubMedGoogle Scholar
  9. Ball C, Krogstad E et al (2012) Drug-eluting fibers for HIV-1 inhibition and contraception. PLoS One 7(11):e49792PubMedCentralPubMedGoogle Scholar
  10. Baloglu E, Ay Senyigit Z et al (2011) In vitro evaluation of mucoadhesive vaginal tablets of antifungal drugs prepared with thiolated polymer and development of a new dissolution technique for vaginal formulations. Chem Pharm Bull (Tokyo) 59(8):952–958Google Scholar
  11. Balzarini J, Van Damme L (2007) Microbicide drug candidates to prevent HIV infection. Lancet 369(9563):787–797PubMedGoogle Scholar
  12. Beigi R, Noguchi L et al (2011) Pharmacokinetics and placental transfer of single-dose tenofovir 1% vaginal gel in term pregnancy. J Infect Dis 204(10):1527–1531PubMedCentralPubMedGoogle Scholar
  13. Bradshaw CS, Pirotta M et al (2012) Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial. PLoS One 7(4):e34540PubMedCentralPubMedGoogle Scholar
  14. Buckheit RW Jr, Watson KM et al (2010) Development of topical microbicides to prevent the sexual transmission of HIV. Antiviral Res 85(1):142–158PubMedCentralPubMedGoogle Scholar
  15. Cao H, Jiang X et al (2010) RNA interference by nanofiber-based siRNA delivery system. J Control Release 144(2):203–212PubMedGoogle Scholar
  16. Chandra A, Mosher WD et al (2011) Sexual behavior, sexual attraction, and sexual identity in the United States: data from the 2006–2008 national survey of family growth. Natl Health Stat Rep 36:1–36Google Scholar
  17. Chatterjee A, Bhowmik B et al (2010) Prolong release bioadhesive vaginal film of anti-HIV drug (Zidovudine): formualtion and in-vitro evaluation. Int J Pharm Sci Res 1(3):28–37Google Scholar
  18. Chen D, Sun K et al (2012) pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system. Int J Nanomed 7:2621–2630Google Scholar
  19. Chiu JB, Liu C et al (2007) Functionalization of poly(L-lactide) nanofibrous scaffolds with bioactive collagen molecules. J Biomed Mater Res A 83(4):1117–1127PubMedGoogle Scholar
  20. Clark M, Hadd S et al (2011) Pharmacokinetics of a fast-dissolve tenofovir vaginal tablet in a rabbit model AAPS meeting. Washington, DCGoogle Scholar
  21. Clark M, Doncel G et al (2012) Development and preclinical pharmacokinetic evaluation of a tenofovir fast-dissolve vaginal tablet. Microbicides 2012, Sydney, AustraliaGoogle Scholar
  22. Cole AM, Patton DL et al (2010) The formulated microbicide RC-101 was safe and antivirally active following intravaginal application in pigtailed macaques. PLoS One 5(11):e15111PubMedCentralPubMedGoogle Scholar
  23. Courtney T, Sacks MS et al (2006) Design and analysis of tissue engineering scaffolds that mimic soft tissue mechanical anisotropy. Biomaterials 27(19):3631–3638PubMedGoogle Scholar
  24. Creatsas G, Guerrero E et al (2001) A multinational evaluation of the efficacy, safety and acceptability of the protectaid contraceptive sponge. Eur J Contracept Reprod Health Care 6(3):172–182PubMedGoogle Scholar
  25. Cui W, Li X et al (2006) Investigation of drug release and matrix degradation of electrospun poly(DL-lactide) fibers with paracetanol inoculation. Biomacromolecules 7(5):1623–1629PubMedGoogle Scholar
  26. Dobaria N, Mashru R (2010) Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clindamycin phosphate. Pharm Dev Technol 15(4):405–414PubMedGoogle Scholar
  27. Dobaria NB, Badhan AC et al (2009) A novel itraconazole bioadhesive film for vaginal delivery: design, optimization, and physicodynamic characterization. AAPS PharmSciTech 10(3):951–959PubMedCentralPubMedGoogle Scholar
  28. Duncan G (1970) Medicated devices and methods. US Patent Number 3, 439Google Scholar
  29. Escobar-Chavez JJ, Lopez-Cervantes M et al (2006) Applications of thermo-reversible pluronic F-127 gels in pharmaceutical formulations. J Pharm Pharm Sci 9(3):339–358PubMedGoogle Scholar
  30. Fan M, Ferguson L, Rohan L, Meyn L, Hillier S (2011) Social and behavioural aspects of prevention poster session 9: Women P2-S9.06 Vaginal film microbicides for HIV prevention: a mixed methods study of women's preferences. Sex Transm Infect 87:A263. http://sti.bmj.com/content/87/Suppl_1/A263.1. doi: 10.1136/sextrans-2011-050108.392 Google Scholar
  31. Fares H, Zatz J (1995) Measurement of drug release from topical gels using two types of apparatus. Pharm Technol 19(1):52–58Google Scholar
  32. FDA (1997) Guidance for industry, nonsterile semisolid dosage forms, scale-up and postapproval changes: chemistry, manufacturing, and controls. In vitro release testing and in vivo bioequivalence documentationGoogle Scholar
  33. Feng K, Sun H et al (2010) Novel antibacterial nanofibrous PLLA scaffolds. J Control Release 146(3):363–369PubMedCentralPubMedGoogle Scholar
  34. Fetherston SM, Malcolm RK et al (2010) Controlled-release vaginal ring drug-delivery systems: a key strategy for the development of effective HIV microbicides. Ther Deliv 1(6):785–802PubMedGoogle Scholar
  35. Fletcher P, Harman S et al (2009) Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother 53(2):487–495PubMedCentralPubMedGoogle Scholar
  36. Foran TM (2003) New contraceptive choices across reproductive life. Med J Aust 178(12):616–620PubMedGoogle Scholar
  37. Forbes CJ, Lowry D et al (2011) Non-aqueous silicone elastomer gels as a vaginal microbicide delivery system for the HIV-1 entry inhibitor maraviroc. J Control Release 156(2):161–169PubMedCentralPubMedGoogle Scholar
  38. Gallagher SJ, Trottet L et al (2003) Ketoprofen: release from, permeation across and rheology of simple gel formulations that simulate increasing dryness. Int J Pharm 268(1–2):37–45PubMedGoogle Scholar
  39. Garg S, Anderson RA et al (2001) Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM). Contraception 64(1):67–75PubMedGoogle Scholar
  40. Garg S, Vermani K et al (2005) Development and characterization of bioadhesive vaginal films of sodium polystyrene sulfonate (PSS), a novel contraceptive antimicrobial agent. Pharm Res 22(4):584–595PubMedGoogle Scholar
  41. Garg S, Goldman D et al (2010) Advances in development, scale-up and manufacturing of microbicide gels, films, and tablets. Antiviral Res 88(Suppl 1):S19–S29PubMedGoogle Scholar
  42. Gohel MC, Jogani PD (2005) A review of co-processed directly compressible excipients. J Pharm Pharm Sci 8(1):76–93PubMedGoogle Scholar
  43. Greiner A, Wendorff JH (2007) Electrospinning: a fascinating method for the preparation of ultrathin fibers. Angew Chem Int Ed Engl 46(30):5670–5703PubMedGoogle Scholar
  44. Gupta P, Vermani K et al (2002) Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discov Today 7(10):569–579PubMedGoogle Scholar
  45. Gupta KM, Pearce SM et al (2008) Polyurethane intravaginal ring for controlled delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1. J Pharm Sci 97(10):4228–4239PubMedGoogle Scholar
  46. Gupta J, Othman A et al (2011) Development and validation of a HPLC method for simultaneous determination of dapivirine and DS003 in combination microbicide tablet. Curr Pharm Anal 7(1):21–26Google Scholar
  47. Ham AS, Rohan LC et al (2012) Vaginal film drug delivery of the pyrimidinedione IQP-0528 for the prevention of HIV infection. Pharm Res 29(7):1897–1907PubMedGoogle Scholar
  48. Han YA, Singh M et al (2007) Development of vaginal rings for sustained release of nonhormonal contraceptives and anti-HIV agents. Contraception 76(2):132–138PubMedGoogle Scholar
  49. Hariharan M, Bogue BA (2009) Orally dissolving film strips (ODFS): the final evolution of orally dissolving dosage forms. Drug Deliv Technol 9(2):24–29Google Scholar
  50. Herrera C, Shattock RJ (2013) Candidate microbicides and their mechanisms of action. Curr Top Microbiol Immunol. http://link.springer.com/chapter/10.1007%2F82_2013_326. doi: 10.1007/82_2013_326. Epub ahead of printGoogle Scholar
  51. Holt JDS, Nuttall JP (2013) Preclinical safety evaluation. Curr Top Microbiol Immunol. doi: 10.1007/82_2013_327 PubMedGoogle Scholar
  52. Huang ZM, He CL et al (2006) Encapsulating drugs in biodegradable ultrafine fibers through co-axial electrospinning. J Biomed Mater Res A 77(1):169–179PubMedGoogle Scholar
  53. Hussain A, Ahsan F (2005) The vagina as a route for systemic drug delivery. J Control Release 103(2):301–313PubMedGoogle Scholar
  54. Ionescu LC, Lee GC et al (2010) An anisotropic nanofiber/microsphere composite with controlled release of biomolecules for fibrous tissue engineering. Biomaterials 31(14):4113–4120PubMedCentralPubMedGoogle Scholar
  55. Iyer V, Poddar SS (2008) Update on nonoxynol-9 as vaginal spermicide. Eur J Contracept Reprod Health Care 13(4):339–350PubMedGoogle Scholar
  56. Jespers VA, Van Roey JM et al (2007) Dose-ranging phase 1 study of TMC120, a promising vaginal microbicide, in HIV-negative and HIV-positive female volunteers. J Acquir Immune Defic Syndr 44(2):154–158PubMedGoogle Scholar
  57. Jiang H, Hu Y et al (2005) A facile technique to prepare biodegradable coaxial electrospun nanofibers for controlled release of bioactive agents. J Control Release 108(2–3):237–243PubMedGoogle Scholar
  58. Jin Q, Wei G et al (2008) Nanofibrous scaffolds incorporating PDGF-BB microspheres induce chemokine expression and tissue neogenesis in vivo. PLoS One 3(3):e1729PubMedCentralPubMedGoogle Scholar
  59. Joglekar NS, Joshi SN et al (2006) Acceptability of Praneem polyherbal vaginal tablet among HIV uninfected women & their male partners in Pune, India–Phase I study. Indian J Med Res 123(4):547–552PubMedGoogle Scholar
  60. Johansson ED (2000) The return of the pharmaceutical industry to the market of contraception. Steroids 65(10–11):709–711PubMedGoogle Scholar
  61. Johnson TJ, Gupta KM et al (2010) Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir. Eur J Pharm Sci 39(4):203–212PubMedGoogle Scholar
  62. Johnson TJ, Srinivasan P et al (2012) Safe and sustained vaginal delivery of pyrimidinedione HIV-1 inhibitors from polyurethane intravaginal rings. Antimicrob Agents Chemother 56(3):1291–1299PubMedCentralPubMedGoogle Scholar
  63. Joshi SN, Katti U et al (2005) Phase I safety study of Praneem polyherbal vaginal tablet use among HIV-uninfected women in Pune, India. Trans R Soc Trop Med Hyg 99(10):769–774PubMedGoogle Scholar
  64. Kalichman SC, Simbayi LC et al (2009) Heterosexual anal intercourse among community and clinical settings in Cape Town, South Africa. Sex Transm Infect 85(6):411–415PubMedCentralPubMedGoogle Scholar
  65. Kawarkhe S, Poddar SS (2010) Designing of the mucoadhesive intravaginal spermicidal films. Indian J Pharm Sci 72(5):652–655. doi: 10.4103/0250-474X.78540 (PMCID: PMC3116316)Google Scholar
  66. Keller MJ, Madan RP et al (2011) A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel. PLoS One 6(1):e16475PubMedCentralPubMedGoogle Scholar
  67. Kidoaki S, Kwon IK et al (2005) Mesoscopic spatial designs of nano- and microfiber meshes for tissue-engineering matrix and scaffold based on newly devised multilayering and mixing electrospinning techniques. Biomaterials 26(1):37–46PubMedGoogle Scholar
  68. Kidoaki S, Kwon IK et al (2006) Structural features and mechanical properties of in situ-bonded meshes of segmented polyurethane electrospun from mixed solvents. J Biomed Mater Res B Appl Biomater 76(1):219–229PubMedGoogle Scholar
  69. Kim HS, Yoo HS (2010) MMPs-responsive release of DNA from electrospun nanofibrous matrix for local gene therapy: in vitro and in vivo evaluation. J Control Release 145(3):264–271PubMedGoogle Scholar
  70. Kiser PF, Johnson TJ et al (2012) State of the art in intravaginal ring technology for topical prophylaxis of HIV infection. AIDS Rev 14(1):62–77PubMedGoogle Scholar
  71. Kumar P, Sanghvi P, Collins CC (1993) Comparison of diffusion studies of hydrocortisone between the Franz cell and the enhancer cell. Drug Dev Ind Pharm 19(13):1573–1585Google Scholar
  72. Lacey CJ, Woodhall S et al (2010) Unacceptable side-effects associated with a hyperosmolar vaginal microbicide in a phase 1 trial. Int J STD AIDS 21(10):714–717PubMedGoogle Scholar
  73. Lai BE, Geonnotti AR et al (2010) Semi-solid gels function as physical barriers to human immunodeficiency virus transport in vitro. Antiviral Res 88(2):143–151PubMedCentralPubMedGoogle Scholar
  74. Liang D, Luu YK et al (2005) In vitro non-viral gene delivery with nanofibrous scaffolds. Nucleic Acids Res 33(19):e170PubMedCentralPubMedGoogle Scholar
  75. Lichtman AS, Davajan V et al (1973) C-film: a new vaginal contraceptive. Contraception 8(4):291–297Google Scholar
  76. Loxley A, Mitchnick M et al (2011) Ethylene vinyl acetate intravaginal rings for the simultaneous delivery of the antiretroviral UC781 and contraceptive levonorgestrel. Drug Deliv Transl Res 1(3):247–255Google Scholar
  77. Luong-Van E, Grondahl L et al (2006) Controlled release of heparin from poly(epsilon-caprolactone) electrospun fibers. Biomaterials 27(9):2042–2050PubMedGoogle Scholar
  78. Macht DI (1918) On the absorption of drugs and poisons through the vagina. J Pharmacol Exp Ther 10:509–522Google Scholar
  79. Mahalingam A, Smith E et al (2010) Design of a semisolid vaginal microbicide gel by relating composition to properties and performance. Pharm Res 27(11):2478–2491PubMedGoogle Scholar
  80. Mahalingam A, Simmons AP et al (2011) Vaginal microbicide gel for delivery of IQP-0528, a pyrimidinedione analog with a dual mechanism of action against HIV-1. Antimicrob Agents Chemother 55(4):1650–1660PubMedCentralPubMedGoogle Scholar
  81. Major I, Boyd P et al (2012) A dapivirine releasing contraceptive diaphragm. Microbicides 2012, Sydney, Australia.Google Scholar
  82. Major I, Lowry D et al (2010) Development of a microbicide-releasing diaphragm as an HIV prevention strategy. Conf Proc IEEE Eng Med Biol Soc 2010:1089–1092PubMedGoogle Scholar
  83. Malcolm RK, Edwards KL et al (2010) Advances in microbicide vaginal rings. Antiviral Res 88(Suppl 1):S30–39PubMedGoogle Scholar
  84. Maretschek S, Greiner A et al (2008) Electrospun biodegradable nanofiber nonwovens for controlled release of proteins. J Control Release 127(2):180–187PubMedGoogle Scholar
  85. Martin HL, Richardson BA et al (1999) Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 180(6):1863–1868PubMedGoogle Scholar
  86. Mauck CK, Allen S et al (1997a) An evaluation of the amount of nonoxynol-9 remaining in the vagina up to 4 h after insertion of a vaginal contraceptive film (VCF) containing 70 mg nonoxynol-9. Contraception 56(2):103–110PubMedGoogle Scholar
  87. Mauck CK, Baker JM et al (1997b) A phase I comparative study of contraceptive vaginal films containing benzalkonium chloride and nonoxynol-9. Postcoital testing and colposcopy. Contraception 56(2):89–96PubMedGoogle Scholar
  88. Mauck CK, Baker JM et al (1997c) A phase I comparative study of three contraceptive vaginal films containing nonoxynol-9. Postcoital testing and colposcopy. Contraception 56(2):97–102PubMedGoogle Scholar
  89. Mauck RL, Baker BM et al (2009) Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration. Tissue Eng Part B Rev 15(2):171–193PubMedCentralPubMedGoogle Scholar
  90. Mayer KH, Maslankowski LA et al (2006) Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS 20(4):543–551PubMedGoogle Scholar
  91. McGowan I, Hoesley C et al (2013) A phase 1 randomized, double blind, placebo controlled rectal safety and acceptability study of tenofovir 1% gel (MTN-007). PLoS One 8(4):e60147PubMedCentralPubMedGoogle Scholar
  92. Minces LR, McGowan I (2010) Advances in the development of microbicides for the prevention of HIV infection. Curr Infect Dis Rep 12(1):56–62PubMedCentralPubMedGoogle Scholar
  93. Moench TR, Mumper RJ et al (2010) Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse. BMC Infect Dis 10:331PubMedCentralPubMedGoogle Scholar
  94. Morrow KM, Hendrix C (2010) Clinical evaluation of microbicide formulations. Antiviral Res 88(Suppl 1):S40–46PubMedCentralPubMedGoogle Scholar
  95. Moss JA, Malone AM et al (2012) Simultaneous delivery of tenofovir and acyclovir via an intravaginal ring. Antimicrob Agents Chemother 56(2):875–882PubMedCentralPubMedGoogle Scholar
  96. Nel A, Smythe S et al (2009a) Safety and pharmacokinetics of dapivirine delivery from matrix and reservoir intravaginal rings to HIV-negative women. J Acquir Immune Defic Syndr 51(4):416–423PubMedGoogle Scholar
  97. Nel AM, Coplan P et al (2009b) Safety, tolerability, and systemic absorption of dapivirine vaginal microbicide gel in healthy, HIV-negative women. AIDS 23(12):1531–1538PubMedGoogle Scholar
  98. Nel AM, Coplan P et al (2010a) Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women. AIDS Res Hum Retroviruses 26(11):1181–1190Google Scholar
  99. Nel AM, Smythe SC et al (2010b) Pharmacokinetics of 2 dapivirine vaginal microbicide gels and their safety vs. Hydroxyethyl cellulose-based universal placebo gel. J Acquir Immune Defic Syndr 55(2):161–169PubMedGoogle Scholar
  100. Nel AM, Mitchnick LB et al (2011) Acceptability of vaginal film, soft-gel capsule, and tablet as potential microbicide delivery methods among African women. J Womens Health (Larchmt) 20(8):1207–1214Google Scholar
  101. Nerurkar NL, Elliott DM et al (2007) Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus tissue engineering. J Orthop Res 25(8):1018–1028PubMedGoogle Scholar
  102. Neurath AR, Strick N et al (1999) Design of a “microbicide” for prevention of sexually transmitted diseases using “inactive” pharmaceutical excipients. Biologicals 27(1):11–21PubMedGoogle Scholar
  103. Neurath AR, Strick N et al (2001) Cellulose acetate phthalate, a common pharmaceutical excipient, inactivates HIV-1 and blocks the coreceptor binding site on the virus envelope glycoprotein gp120. BMC Infect Dis 1:17PubMedCentralPubMedGoogle Scholar
  104. Neurath AR, Strick N et al (2003) Water dispersible microbicidal cellulose acetate phthalate film. BMC Infect Dis 3:27PubMedCentralPubMedGoogle Scholar
  105. Novak A, de la Loge C et al (2003) The combined contraceptive vaginal ring, NuvaRing: an international study of user acceptability. Contraception 67(3):187–194PubMedGoogle Scholar
  106. O’Dowd MJ (ed) (2001) The history of medications for women: materia medica woman. Taylor & Francis, LondonGoogle Scholar
  107. Okuda T, Tominaga K et al (2010) Time-programmed dual release formulation by multilayered drug-loaded nanofiber meshes. J Control Release 143(2):258–264PubMedGoogle Scholar
  108. Owen DH, Peters JJ et al (2003) Effect of temperature and pH on contraceptive gel viscosity. Contraception 67(1):57–64PubMedGoogle Scholar
  109. Pham Q, Sharma U et al (2006) Electrospinning of polymeric nanofibers for tissue engineering applications: a review. Tissue Eng 12(5):1197–1211PubMedGoogle Scholar
  110. Politz ML, Timpa JD et al (1994) Non-aqueous gel permeation chromatography of wheat starch in dimethylacetamide (DMAC) and LiCl: extrusion-induced fragmentation. Carbohydr Polym 24:91–99Google Scholar
  111. Rad M, Kluft C et al (2006) Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral contraceptive containing levonorgestrel on hemostasis variables. Am J Obstet Gynecol 195(1):72–77PubMedGoogle Scholar
  112. Reeves JD, Piefer AJ (2005) Emerging drug targets for antiretroviral therapy. Drugs 65(13):1747–1766PubMedGoogle Scholar
  113. Reilly B, Bruner S (2004) Silicones as a material of choice for drug delivery applications. In: 31st annual meeting and exposition of the controlled release society, Honolulu, HawaiiGoogle Scholar
  114. Roddy RE, Zekeng L 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(8):504–510PubMedGoogle Scholar
  115. Roumen FJ, Apter D et al (2001) Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol. Hum Reprod 16(3):469–475PubMedGoogle Scholar
  116. Roy S, Gourde P et al (2001) Thermoreversible gel formulations containing sodium lauryl sulfate or n-Lauroylsarcosine as potential topical microbicides against sexually transmitted diseases. Antimicrob Agents Chemother 45(6):1671–1681PubMedCentralPubMedGoogle Scholar
  117. Sam AP, Fokkens JG (1997) Drug delivery system: adding therapeutic and economic value to pharmacotherapy part 2. Pharm Tech Eur 9:58–66Google Scholar
  118. Sassi AB, Isaacs CE et al (2008) Effects of physiological fluids on physical-chemical characteristics and activity of topical vaginal microbicide products. J Pharm Sci 97(8):3123–3139PubMedGoogle Scholar
  119. Sassi AB, Cost MR et al (2011) Formulation development of retrocyclin 1 analog RC-101 as an anti-HIV vaginal microbicide product. Antimicrob Agents Chemother 55(5):2282–2289PubMedCentralPubMedGoogle Scholar
  120. Saxena BB, Han YA et al (2009) Sustained release of microbicides by newly engineered vaginal rings. AIDS 23(8):917–922PubMedGoogle Scholar
  121. Schwartz JL, Ballagh SA et al (2008a) SILCS diaphragm: postcoital testing of a new single-size contraceptive device. Contraception 78(3):237–244PubMedGoogle Scholar
  122. Schwartz JL, Kovalevsky G et al (2008b) A randomized six-day safety study of an antiretroviral microbicide candidate UC781, a non-nucleoside reverse transcriptase inhibitor. Sex Transm Dis 35(4):414–419PubMedGoogle Scholar
  123. Seager H (1998) Drug-delivery products and the Zydis fast-dissolving dosage form. J Pharm Pharmacol 50(4):375–382PubMedGoogle Scholar
  124. Seattle King County Department of Public Health (2000) What is the STD-HIV connection? Accessed June 2000. http://www.metrokc.gov/health/apu/healthed/Powr/HIV_STD/sld003.htm
  125. Seeras RC (1995) Induction of labor utilizing vaginal vs. intracervical prostaglandin E2. Int J Gynaecol Obstet 48(2):163–167PubMedGoogle Scholar
  126. Seeras RC, Olatunbosun OA et al (1995) Induction of labor using prostaglandin E2 (PGE2) vaginal gel in triacetin base. An efficacy study comparing two dosage regimens. Clin Exp Obstet Gynecol 22(2):105–110PubMedGoogle Scholar
  127. Shah VP, Elkins J et al (1989) Determination of in vitro drug release from hydrocortisone creams. Int J Pharm 53(1):53–59Google Scholar
  128. Siewert M, Dressman J et al (2003) FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms. AAPS PharmSciTech 4(1):E7PubMedGoogle Scholar
  129. Skoler-Karpoff S, Ramjee G et al (2008) Efficacy of Carraguard for prevention of HIV infection in women in South Africa: a randomised, double-blind, placebo-controlled trial. Lancet 372(9654):1977–1987PubMedGoogle Scholar
  130. Song Y, Wang Y et al (2004) Mucosal drug delivery: membranes, methodologies, and applications. Crit Rev Ther Drug Carrier Syst 21(3):195–256PubMedGoogle Scholar
  131. Stitzel J, Liu J et al (2006) Controlled fabrication of a biological vascular substitute. Biomaterials 27(7):1088–1094PubMedGoogle Scholar
  132. Sudeendra B, Umme H et al (2010) Development and characterization of bioadhesive vaginal films of clotrimazole for vaginal candidiasis. Acta Pharmaceutica Sciencia 52:417–426Google Scholar
  133. Szycher M (1988) Biostability of polyurethane elastomers: a critical review. J Biomater Appl 3(2):297–402PubMedGoogle Scholar
  134. Taepaiboon P, Rungsardthong U et al (2006) Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs. Nanotechnology 17(9):2317–2329Google Scholar
  135. Tamburic S, Craig DQ (1996) The effects of ageing on the rheological, dielectric and mucoadhesive properties of poly(acrylic acid) gel systems. Pharm Res 13(2):279–283PubMedGoogle Scholar
  136. Tan AR, Ifkovits JL et al (2008) Electrospinning of photocrosslinked and degradable fibrous scaffolds. J Biomed Mater Res A 87(4):1034–1043PubMedGoogle Scholar
  137. Tao W, Richards C et al (2008) Enhancement of HIV infection by cellulose sulfate. AIDS Res Hum Retroviruses 24(7):925–929PubMedCentralPubMedGoogle Scholar
  138. Theron A, Zussman E et al (2001) Electrostatic field-assisted alignment of electrospun nanofibres. Nanotechnology 12:384–390Google Scholar
  139. Thyssen H, Bidmead J et al (2001) A new intravaginal device for stress incontinence in women. BJU Int 88(9):889–892PubMedGoogle Scholar
  140. Trifonova RT, Pasicznyk JM et al (2006) Biocompatibility of solid-dosage forms of anti-human immunodeficiency virus type 1 microbicides with the human cervicovaginal mucosa modeled ex vivo. Antimicrob Agents Chemother 50(12):4005–4010PubMedCentralPubMedGoogle Scholar
  141. Turpin JA (2011) Topical microbicides to prevent the transmission of HIV: formulation gaps and challenges. Drug Deliv Transl Res 1(3):194–200PubMedCentralPubMedGoogle Scholar
  142. van Laarhoven JA, Kruft MA et al (2002a) Effect of supersaturation and crystallization phenomena on the release properties of a controlled release device based on EVA copolymer. J Control Release 82(2–3):309–317PubMedGoogle Scholar
  143. van Laarhoven JA, Kruft MA et al (2002b) In vitro release properties of etonogestrel and ethinyl estradiol from a contraceptive vaginal ring. Int J Pharm 232(1–2):163–173PubMedGoogle Scholar
  144. Ventuneac A, Carballo-Dieguez A et al (2010) Acceptability of UC781 gel as a rectal microbicide among HIV-uninfected women and men. AIDS Behav 14(3):618–628PubMedCentralPubMedGoogle Scholar
  145. Vermani K, Garg S (2000) The scope and potential of vaginal drug delivery. Pharm Sci Technolo Today 3(10):359–364PubMedGoogle Scholar
  146. Virley P, Yarwood R (1990) Zydis-a novel, fast dissolving dosage form. Manufact Chemist 61:36–37Google Scholar
  147. Vondrak B, Barnhart S (2008) Dissolvable films: dissolvable films for flexible product format in drug delivery. Pharm Technol. Accessed http://www.pharmtech.com/pharmtech/Article/Dissolvable-Films-Dissolvable-Films-for-Flexible-P/ArticleStandard/Article/detail/505380
  148. Wang J, Chen C et al (2010) Effect of experimental parameters on the formation of chitosan-Poly(acrylic acid) nanofibrous scaffolds and evaluation of their potential application as DNA carrier. J Appl Polym Sci 155(1769):1769–1780Google Scholar
  149. Weber J, Desai K et al (2005) The development of vaginal microbicides for the prevention of HIV transmission. PLoS Med 2(5):e142PubMedCentralPubMedGoogle Scholar
  150. Wei G, Jin Q et al (2006) Nano-fibrous scaffold for controlled delivery of recombinant human PDGF-BB. J Control Release 112(1):103–110PubMedCentralPubMedGoogle Scholar
  151. Wichterle O, Lim D (1960) Hydrophilic gels for biological use. Nature 185(4706):117–118Google Scholar
  152. Woolfson A, Elliott G et al (1999) Design of an intravaginal ring for the controlled delivery of 17 beta-estradiol as its 3-acetate ester. J Control Release 61(3):319–328PubMedGoogle Scholar
  153. Yang H, Parniak MA et al (2008) Characterization of cyclodextrin inclusion complexes of the anti-HIV non-nucleoside reverse transcriptase inhibitor UC781. AAPS J 10(4):606–613PubMedCentralPubMedGoogle Scholar
  154. Yoo JW, Dharmala K et al (2006) The physicodynamic properties of mucoadhesive polymeric films developed as female controlled drug delivery system. Int J Pharm 309(1–2):139–145PubMedGoogle Scholar
  155. Yoo JW, Acharya G et al (2009) In vivo evaluation of vaginal films for mucosal delivery of nitric oxide. Biomaterials 30(23–24):3978–3985PubMedGoogle Scholar
  156. Zhang W, Parniak MA et al (2012) Formulation, optimization and characterization of a vaginal film containing EFdA, a novel nucleoside reverse transcriptase inhibitor (NRTI), for HIV prevention. 2012 Microbicides, Sydney, AustraliaGoogle Scholar
  157. Zhang YZ, Wang X et al (2006) Coaxial electrospinning of (fluorescein isothiocyanate-conjugated bovine serum albumin)-encapsulated poly(epsilon-caprolactone) nanofibers for sustained release. Biomacromolecules 7(4):1049–1057PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, School of PharmacyUniversity of Pittsburgh Magee Women’s Research InstitutePittsburghUSA
  2. 2.International Partnership for MicrobicidesSilver SpringUSA

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