New strategies for local treatment of vaginal infections

Advanced Drug Delivery Reviews

Volumn 92, Issue , 2015, Pages 105-122

  Palmeira de Oliveira, Rita ^a,b   Palmeira de Oliveira, Ana ^a,b   Martinez de Oliveira, José ^a,c  

^a UNIVERSITY OF BEIRA INTERIOR   (Portugal)

^b Centro Hospitalar Cova da Beira   (Portugal)

^c Centro Hospitalar da Cova da Beira   (Portugal)

Author keywords

Bacterial vaginosis; Bioadhesive formulations; Plant extracts; Thermogelling systems; Trichomoniasis; Vaginal bacteriosis; Vaginal dosage forms; Vulvovaginal candidosis

Indexed keywords

DRUG INTERACTIONS; PLANT EXTRACTS; PROBIOTICS;

BACTERIAL VAGINOSIS; BIO ADHESIVES; DOSAGE FORMS; THERMOGELLING; TRICHOMONIASIS; VAGINAL BACTERIOSIS; VULVOVAGINAL CANDIDOSIS;

DRUG DELIVERY;

BENZYDAMINE; CARBOMER; CHITOSAN; CHLORHEXIDINE; CLOTRIMAZOLE; ECONAZOLE; ESSENTIAL OIL; FLUCONAZOLE; GARLIC EXTRACT; HYALURONIC ACID; HYDROXYETHYLCELLULOSE; HYDROXYPROPYLCELLULOSE; HYDROXYPROPYLMETHYLCELLULOSE; KETOCONAZOLE; MERCAPTAMINE; METRONIDAZOLE; MICONAZOLE NITRATE; NYSTATIN; ONION EXTRACT; PECTIN; PLACEBO; POLYACRYLIC ACID; POLYCARBOPHIL; PREBIOTIC AGENT; PROBIOTIC AGENT; RIFAXIMIN; STARCH; TEA TREE OIL; THIOGLYCOLIC ACID; UNINDEXED DRUG; AGENTS USED INTRAVAGINALLY; ANTIINFECTIVE AGENT;

AEROBIC VAGINITIS; BIOADHESION; DRUG DELIVERY SYSTEM; FILM; GEL; HUMAN; LACTOBACILLUS ACIDOPHILUS; MICROTECHNOLOGY; NANOTECHNOLOGY; PRIORITY JOURNAL; REVIEW; TABLET; THERMOGELLING SYSTEM; TRICHOMONIASIS; VAGINA CANDIDIASIS; VAGINITIS; CANDIDIASIS, VULVOVAGINAL; DRUG ABSORPTION; FEMALE; INTRAVAGINAL DRUG ADMINISTRATION; PHARMACEUTICS; PHYSIOLOGY; PROCEDURES; TRICHOMONAS VAGINITIS; VAGINA; VAGINOSIS, BACTERIAL;

ADMINISTRATION, INTRAVAGINAL; ANTI-BACTERIAL AGENTS; CANDIDIASIS, VULVOVAGINAL; DRUG DELIVERY SYSTEMS; FEMALE; HUMANS; OILS, VOLATILE; PROBIOTICS; TECHNOLOGY, PHARMACEUTICAL; TRICHOMONAS VAGINITIS; VAGINA; VAGINAL ABSORPTION; VAGINAL CREAMS, FOAMS, AND JELLIES; VAGINITIS; VAGINOSIS, BACTERIAL;

EID: 84943448612     PISSN: 0169409X     EISSN: 18728294     Source Type: Journal    
DOI: 10.1016/j.addr.2015.06.008     Document Type: Review

References (237)

1. Donders G.G. Definition and classification of abnormal vaginal flora. Best Pract. Res. Clin. Obstet. Gynaecol. 2007, 21:355-373.
2. Mardh P.A., Rodrigues A.G., Genc M., Novikova N., Martinez-de-Oliveira J., Guaschino S. Facts and myths on recurrent vulvovaginal candidosis-a review on epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy. Int. J. STD AIDS 2002, 13:522-539.
3. Nappi R.E., Liekens G., Brandenburg U. Attitudes, perceptions and knowledge about the vagina: the International Vagina Dialogue Survey. Contraception 2006, 73:493-500.
4. Palmeira-de-Oliveira R., Duarte P., Palmeira-de-Oliveira A., das Neves J., Amaral M.H., Breitenfeld L., Martinez-de-Oliveira J. Women's experiences, preferences and perceptions regarding vaginal products: results from a cross-sectional web-based survey in Portugal. Eur. J. Contracept. Reprod. Health Care 2014, 1-13.
5. Karasz A., Anderson M. The vaginitis monologues: women's experiences of vaginal complaints in a primary care setting. Soc. Sci. Med. 2003, 56:1013-1021.
6. Bilardi J.E., Walker S., Temple-Smith M., McNair R., Mooney-Somers J., Bellhouse C., Fairley C.K., Chen M.Y., Bradshaw C. The burden of bacterial vaginosis: women's experience of the physical, emotional, sexual and social impact of living with recurrent bacterial vaginosis. PLoS One 2013, 8.
7. das Neves J., Palmeira-de-Oliveira R., Palmeira-de-Oliveira A., Rodrigues F., Sarmento B. Vaginal mucosa and drug delivery. Mucoadhesive Materials and Drug Delivery Systems 2014, 99-131. Wiley, Chichester, UK. V. Khutoryanskiy (Ed.).
8. Owen D.H., Katz D.F. A vaginal fluid simulant. Contraception 1999, 59:91-95.
9. Spear G.T., French A.L., Gilbert D., Zariffard M.R., Mirmonsef P., Sullivan T.H., Spear W.W., Landay A., Micci S., Lee B.H., Hamaker B.R. Human alpha-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus. J. Infect. Dis. 2014, 210:1019-1028.
10. O'Dowd M.J. The History of Medications for Women: Materia Medica Woman 2001, Taylor & Francis, London, UK.
11. Vermani K., Garg S. The scope and potential of vaginal drug delivery. Pharm. Sci. Technol. Today 2000, 3:359-364.
12. Hussain A., Ahsan F. The vagina as a route for systemic drug delivery. J. Control. Release 2005, 103:301-313.
13. das Neves J., Bahia M.F. Gels as vaginal drug delivery systems. Int. J. Pharm. 2006, 318:1-14.
14. Acarturk F. Mucoadhesive vaginal drug delivery systems. Recent Pat. Drug Deliv. Formul. 2009, 3:193-205.
15. Valenta C. The use of mucoadhesive polymers in vaginal delivery. Adv. Drug Deliv. Rev. 2005, 57:1692-1712.
16. Al-Fattani M.A., Douglas L.J. Penetration of Candida biofilms by antifungal agents. Antimicrob. Agents Chemother. 2004, 48:3291-3297.
17. Ramage G., Saville S.P., Thomas D.P., Lopez-Ribot J.L. Candida biofilms: an update. Eukaryot. Cell 2005, 4:633-638.
18. Patterson J.L., Girerd P.H., Karjane N.W., Jefferson K.K. Effect of biofilm phenotype on resistance of Gardnerella vaginalis to hydrogen peroxide and lactic acid. Am. J. Obstet. Gynecol. 2007, 170:e171-e177.
19. Swidsinski A., Mendling W., Loening-Baucke V., Swidsinski S., Dorffel Y., Scholze J., Lochs H., Verstraelen H. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am. J. Obstet. Gynecol. 2008, 97:e91-e96.
20. Smayevsky J., Canigia L.F., Lanza A., Bianchini H. Vaginal microflora associated with bacterial vaginosis in nonpregnant women: reliability of sialidase detection. Infect. Dis. Obstet. Gynecol. 2001, 9:17-22.
21. Ferris M.J., Masztal A., Aldridge K.E., Fortenberry J.D., Fidel P.L., Martin D.H. Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis. BMC Infect. Dis. 2004, 4:5.
22. Verhelst R., Verstraelen H., Claeys G., Verschraegen G., Delanghe J., Van Simaey L., De Ganck C., Temmerman M., Vaneechoutte M. Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMC Microbiol. 2004, 4:16.
23. Fredricks D.N., Fiedler T.L., Marrazzo J.M. Molecular identification of bacteria associated with bacterial vaginosis. N. Engl. J. Med. 2005, 353:1899-1911.
24. Biagi E., Vitali B., Pugliese C., Candela M., Donders G.G., Brigidi P. Quantitative variations in the vaginal bacterial population associated with asymptomatic infections: a real-time polymerase chain reaction study. Eur. J. Clin. Microbiol. Infect. Dis. 2009, 28:281-285.
25. 2-producing Lactobacillus among women with bacterial vaginosis. J. Infect. Dis. 2005, 191:924-929.
26. Martinez Oliveira J. Bacterial vaginosis and candidosis. Arq. Med. 1993, 7:194-195.
27. Huth E. Style notes: bacterial vaginosis or vaginal bacteriosis?. Ann. Intern. Med. 1989, 111:553.
28. Gardner H.L., Dukes C.D. Haemophilus vaginalis vaginitis: a newly defined specific infection previously classified non-specific vaginitis. Am. J. Obstet. Gynecol. 1955, 69:962-976.
29. Sobel J.D. Bacterial vaginosis. Annu. Rev. Med. 2000, 51:349-356.
30. Schmid G.P. The epidemiology of bacterial vaginosis. Int. J. Gynaecol. Obstet. 1999, 67(Suppl. 1):S17-S20.
31. C.D.C.Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines 2010, vol. 59, No. RR-12. (Atlanta).
32. Schwebke J.R., Desmond R.A., Oh M.K. Predictors of bacterial vaginosis in adolescent women who douche. Sex. Transm. Dis. 2004, 31:433-436.
33. Haggerty C.L., Hillier S.L., Bass D.C., Ness R.B. Bacterial vaginosis and anaerobic bacteria are associated with endometritis. Clin. Infect. Dis. 2004, 39:990-995.
34. Hay P.E., Lamont R.F., Taylor-Robinson D., Morgan D.J., Ison C., Pearson J. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ 1994, 308:295-298.
35. Spiegel C.A. Bacterial vaginosis. Clin. Microbiol. Rev. 1991, 4:485-502.
36. Amsel R., Totten P.A., Spiegel C.A., Chen K.C., Eschenbach D., Holmes K.K. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am. J. Med. 1983, 74:14-22.
37. Nugent R.P., Krohn M.A., Hillier S.L. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J. Clin. Microbiol. 1991, 29:297-301.
38. Vitali B., Pugliese C., Biagi E., Candela M., Turroni S., Bellen G., Donders G.G., Brigidi P. Dynamics of vaginal bacterial communities in women developing bacterial vaginosis, candidiasis, or no infection, analyzed by PCR-denaturing gradient gel electrophoresis and real-time PCR. Appl. Environ. Microbiol. 2007, 73:5731-5741.
39. Ratnam S., Fitzgerald B.L. Semiquantitative culture of Gardnerella vaginalis in laboratory determination of nonspecific vaginitis. J. Clin. Microbiol. 1983, 18:344-347.
40. Alves P., Castro J., Sousa C., Cereija T.B., Cerca N. Gardnerella vaginalis outcompetes 29 other bacterial species isolated from patients with bacterial vaginosis, using in an in vitro biofilm formation model. J. Infect. Dis. 2014, 210:593-596.
41. Patterson J.L., Stull-Lane A., Girerd P.H., Jefferson K.K. Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes. Microbiology 2010, 156:392-399.
42. Olmsted S.S., Meyn L.A., Rohan L.C., Hillier S.L. Glycosidase and proteinase activity of anaerobic gram-negative bacteria isolated from women with bacterial vaginosis. Sex. Transm. Dis. 2003, 30:257-261.
43. Ferris D.G., Litaker M.S., Woodward L., Mathis D., Hendrich J. Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J. Fam. Pract. 1995, 41:443-449.
44. Mikamo H., Kawazoe K., Izumi K., Watanabe K., Ueno K., Tamaya T. Comparative study on vaginal or oral treatment of bacterial vaginosis. Chemotherapy 1997, 43:60-68.
45. Bradshaw C.S., Morton A.N., Hocking J., Garland S.M., Morris M.B., Moss L.M., Horvath L.B., Kuzevska I., Fairley C.K. High recurrence rates of bacterial vaginosis over the course of 12months after oral metronidazole therapy and factors associated with recurrence. J. Infect. Dis. 2006, 193:1478-1486.
46. Austin M.N., Beigi R.H., Meyn L.A., Hillier S.L. Microbiologic response to treatment of bacterial vaginosis with topical clindamycin or metronidazole. J. Clin. Microbiol. 2005, 43:4492-4497.
47. Beigi R.H., Austin M.N., Meyn L.A., Krohn M.A., Hillier S.L. Antimicrobial resistance associated with the treatment of bacterial vaginosis. Am. J. Obstet. Gynecol. 2004, 191:1124-1129.
48. Donders G.G., Vereecken A., Bosmans E., Dekeersmaecker A., Salembier G., Spitz B. Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis. BJOG 2002, 109:34-43.
49. Tansarli G.S., Kostaras E.K., Athanasiou S., Falagas M.E. Prevalence and treatment of aerobic vaginitis among non-pregnant women: evaluation of the evidence for an underestimated clinical entity. Eur. J. Clin. Microbiol. Infect. Dis. 2013, 32:977-984.
50. Tempera G., Bonfiglio G., Cammarata E., Corsello S., Cianci A. Microbiological/clinical characteristics and validation of topical therapy with kanamycin in aerobic vaginitis: a pilot study. Int. J. Antimicrob. Agents 2004, 24:85-88.
51. Sobel J.D. Epidemiology and pathogenesis of recurrent vulvovaginal candidiasis. Am. J. Obstet. Gynecol. 1985, 152:924-935.
52. Hurley R., De Louvois J. Candida vaginitis. Postgrad. Med. J. 1979, 55:645-647.
53. Foxman B., Marsh J.V., Gillespie B., Sobel J.D. Frequency and response to vaginal symptoms among white and African American women: results of a random digit dialing survey. J. Women's Health 1998, 7:1167-1174.
54. Eckert L.O., Hawes S.E., Stevens C.E., Koutsky L.A., Eschenbach D.A., Holmes K.K. Vulvovaginal candidiasis: clinical manifestations, risk factors, management algorithm. Obstet. Gynecol. 1998, 92:757-765.
55. Sobel J.D. Vulvovaginal candidosis. Lancet 2007, 369:1961-1971.
56. Mendling W. Vulvovaginal candidosis. Theory and Practice 1988, Springer-Verlag, Berlin. 1st ed.
57. Sobel J.D. Pathogenesis and epidemiology of vulvovaginal candidiasis. Ann. N. Y. Acad. Sci. 1988, 544:547-557.
58. Valore E.V., Park C.H., Igreti S.L., Ganz T. Antimicrobial components of vaginal fluid. Am. J. Obstet. Gynecol. 2002, 187:561-568.
59. Garcia-Tamayo J., Castillo G., Martinez A.J. Human genital candidiasis: histochemistry, scanning and transmission electron microscopy. Acta Cytol. 1982, 26:7-14.
60. Beikert F.C., Le M.T., Koeninger A., Technau K., Clad A. Recurrent vulvovaginal candidosis: focus on the vulva. Mycoses 2011, 54:e807-e810.
61. El-Din S., Reynolds M., Ashbee H., Barton R., Evans E. An investigation into the pathogenesis of vulvo-vaginal candidosis. Sex. Transm. Infect. 2001, 77:179-183.
62. Mardh P.A., Novikova N., Stukalova E. Colonisation of extragenital sites by Candida in women with recurrent vulvovaginal candidosis. BJOG 2003, 110:934-937.
63. Fidel P.L., Sobel J.D. Immunopathogenesis of recurrent vulvovaginal candidiasis. Clin. Microbiol. Rev. 1996, 9:335-348.
64. Chandra J., Kuhn D.M., Mukherjee P.K., Hoyer L.L., McCormick T., Ghannoum M.A. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J. Bacteriol. 2001, 183:5385-5394.
65. Lamfon H., Porter S.R., McCullough M., Pratten J. Susceptibility of Candida albicans biofilms grown in a constant depth film fermentor to chlorhexidine, fluconazole and miconazole: a longitudinal study. J. Antimicrob. Chemother. 2004, 53:383-385.
66. Pappas P.G., Rex J.H., Sobel J.D., Filler S.G., Dismukes W.E., Walsh T.J., Edwards J.E. Guidelines for treatment of candidiasis. Clin. Infect. Dis. 2004, 38:161-189.
67. Donders G.G., Bellen G., Mendling W. Management of recurrent vulvo-vaginal candidosis as a chronic illness. Gynecol. Obstet. Investig. 2010, 70:306-321.
68. Donders G., Bellen G., Byttebier G., Verguts L., Hinoul P., Walckiers R., Stalpaert M., Vereecken A., Van Eldere J. Individualized decreasing-dose maintenance fluconazole regimen for recurrent vulvovaginal candidiasis (ReCiDiF trial). Am. J. Obstet. Gynecol. 2008, 199:613.e1-613.e9.
69. Ray D., Goswami R., Banerjee U., Dadhwal V., Goswami D., Mandal P., Sreenivas V., Kochupillai N. Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis. Diabetes Care 2007, 30:312-317.
70. Sobel J.D., Kapernick P.S., Zervos M., Reed B.D., Hooton T., Soper D., Nyirjesy P., Heine M.W., Willems J., Panzer H., Wittes H. Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole. Am. J. Obstet. Gynecol. 2001, 185:363-369.
71. Shahid Z., Sobel J.D. Reduced fluconazole susceptibility of Candida albicans isolates in women with recurrent vulvovaginal candidiasis: effects of long-term fluconazole therapy. Diagn. Microbiol. Infect. Dis. 2009, 64:354-356.
72. W.World Health Organization Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections Overview and Estimates 2001, (Geneva).
73. Sutton M., Sternberg M., Koumans E.H., McQuillan G., Berman S., Markowitz L. The prevalence of Trichomonas vaginalis infection among reproductive-age women in the United States, 2001-2004. Clin. Infect. Dis. 2007, 45:1319-1326.
74. Pastorek J.G., Cotch M.F., Martin D.H., Eschenbach D.A. Clinical and microbiological correlates of vaginal trichomoniasis during pregnancy. The Vaginal Infections and Prematurity Study Group. Clin. Infect. Dis. 1996, 23:1075-1080.
75. Lehker M.W., Alderete J.F. Biology of trichomonosis. Curr. Opin. Infect. Dis. 2000, 13:37-45.
76. Mendoza-Lopez M.R., Becerril-Garcia C., Fattel-Facenda L.V., Avila-Gonzalez L., Ruiz-Tachiquin M.E., Ortega-Lopez J., Arroyo R. CP30, a cysteine proteinase involved in Trichomonas vaginalis cytoadherence. Infect. Immun. 2000, 68:4907-4912.
77. Hernandez H., Sariego I., Garber G., Delgado R., Lopez O., Sarracent J. Monoclonal antibodies against a 62kDa proteinase of Trichomonas vaginalis decrease parasite cytoadherence to epithelial cells and confer protection in mice. Parasite Immunol. 2004, 26:119-125.
78. Fichorova R.N., Buck O.R., Yamamoto H.S., Fashemi T., Dawood H.Y., Fashemi B., Hayes G.R., Beach D.H., Takagi Y., Delaney M.L., Nibert M.L., Singh B.N., Onderdonk A.B. The villain team-up or how Trichomonas vaginalis and bacterial vaginosis alter innate immunity in concert. Sex. Transm. Infect. 2013, 89:460-466.
79. Forna F., Gulmezoglu A.M. Interventions for treating trichomoniasis in women. Cochrane Database Syst. Rev. 2003, 10.1002/14651858.CD000218.
80. Schmid G., Narcisi E., Mosure D., Secor W.E., Higgins J., Moreno H. Prevalence of metronidazole-resistant Trichomonas vaginalis in a gynecology clinic. J. Reprod. Med. 2001, 46:545-549.
81. Schwebke J.R., Barrientes F.J. Prevalence of Trichomonas vaginalis isolates with resistance to metronidazole and tinidazole. Antimicrob. Agents Chemother. 2006, 50:4209-4210.
82. Petrin D., Delgaty K., Bhatt R., Garber G. Clinical and microbiological aspects of Trichomonas vaginalis. Clin. Microbiol. Rev. 1998, 11:300-317.
83. Chang J.Y., Oh Y.K., Choi H.G., Kim Y.B., Kim C.K. Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. Int. J. Pharm. 2002, 241:155-163.
84. Owen D.H., Peters J.J., Lavine M.L., Katz D.F. Effect of temperature and pH on contraceptive gel viscosity. Contraception 2003, 67:57-64.
85. Aka-Any-Grah A., Bouchemal K., Koffi A., Agnely F., Zhang M., Djabourov M., Ponchel G. Formulation of mucoadhesive vaginal hydrogels insensitive to dilution with vaginal fluids. Eur. J. Pharm. Biopharm. 2010, 76:296-303.
86. Sassi A.B., Isaacs C.E., Moncla B.J., Gupta P., Hillier S.L., Rohan L.C. Effects of physiological fluids on physical-chemical characteristics and activity of topical vaginal microbicide products. J. Pharm. Sci. 2008, 97:3123-3139.
87. Mirza M.A., Ahmad S., Mallick M.N., Manzoor N., Talegaonkar S., Iqbal Z. Development of a novel synergistic thermosensitive gel for vaginal candidiasis: an in vitro, in vivo evaluation. Colloids Surf. B: Biointerfaces 2013, 103:275-282.
88. Bachhav Y.G., Patravale V.B. Microemulsion-based vaginal gel of clotrimazole: formulation, in vitro evaluation, and stability studies. AAPS PharmSciTech 2009, 10:476-481.
89. Bachhav Y.G., Patravale V.B. Microemulsion based vaginal gel of fluconazole: formulation, in vitro and in vivo evaluation. Int. J. Pharm. 2009, 365:175-179.
90. Cevher E., Acma A., Sinani G., Aksu B., Zloh M., Mulazimoglu L. Bioadhesive tablets containing cyclodextrin complex of itraconazole for the treatment of vaginal candidiasis. Int. J. Biol. Macromol. 2014, 69:124-136.
91. Francois M., Snoeckx E., Putteman P., Wouters F., De Proost E., Delaet U., Peeters J., Brewster M.E. A mucoadhesive, cyclodextrin-based vaginal cream formulation of itraconazole. AAPS PharmSci 2003, 5.
92. Bilensoy E., Rouf M.A., Vural I., Hincal A.A. Thermosensitive vaginal gel formulation for the controlled release of clotrimazole via complexation to beta-cyclodextrin. J. Control. Release 2006, 116:e107-e109.
93. Kim Y.T., Shin B.K., Garripelli V.K., Kim J.K., Davaa E., Jo S., Park J.S. A thermosensitive vaginal gel formulation with HPgammaCD for the pH-dependent release and solubilization of amphotericin B. Eur. J. Pharm. Sci. 2010, 41:399-406.
94. Lawrence M.J., Rees G.D. Microemulsion-based media as novel drug delivery systems. Adv. Drug Deliv. Rev. 2000, 45:89-121.
95. Thompson D.O. Cyclodextrins-enabling excipients: their present and future use in pharmaceuticals. Crit. Rev. Ther. Drug Carrier Syst. 1997, 14:1-104.
96. Barnhart K., Pretorius E.S., Stolpen A., Malamud D. Distribution of topical medication in the human vagina as imaged by magnetic resonance imaging. Fertil. Steril. 2001, 76:189-195.
97. Brown J., Hooper G., Kenyon C.J., Haines S., Burt J., Humphries J.M., Newman S.P., Davis S.S., Sparrow R.A., Wilding I.R. Spreading and retention of vaginal formulations in post-menopausal women as assessed by gamma scintigraphy. Pharm. Res. 1997, 14:1073-1078.
98. Barnhart K.T., Pretorius E.S., Timbers K., Shera D., Shabbout M., Malamud D. In vivo distribution of a vaginal gel: MRI evaluation of the effects of gel volume, time and simulated intercourse. Contraception 2004, 70:498-505.
99. Omar R.F., Trottier S., Brousseau G., Ouellet C., Danylo A., Ong T., Bergeron M.G. Universal vaginal applicator for the uniform distribution of vaginal gel and cream formulations: a magnetic resonance imaging study. J. Obstet. Gynaecol. Can. 2014, 36:42-50.
100. Smart J.D. The basics and underlying mechanisms of mucoadhesion. Adv. Drug Deliv. Rev. 2005, 57:1556-1568.
101. Ahmad F.J., Alam M.A., Khan Z.I., Khar R.K., Ali M. Development and in vitro evaluation of an acid buffering bioadhesive vaginal gel for mixed vaginal infections. Acta Pharma. 2008, 58:407-419.
102. Alam M.A., Ahmad F.J., Khan Z.I., Khar R.K., Ali M. Development and evaluation of acid-buffering bioadhesive vaginal tablet for mixed vaginal infections. AAPS PharmSciTech 2007, 8.
103. Kast C.E., Valenta C., Leopold M., Bernkop-Schnurch A. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J. Control. Release 2002, 81:347-354.
104. Szymanska E., Winnicka K., Amelian A., Cwalina U. Vaginal chitosan tablets with clotrimazole-design and evaluation of mucoadhesive properties using porcine vaginal mucosa, mucin and gelatine. Chem. Pharm. Bull. 2014, 62:160-167.
105. Cecshel G.C., Maffei P., Borgia S.L., Ronchi C., Rossi S. Development of a mucoadhesive dosage form for vaginal administration. Drug Dev. Ind. Pharm. 2001, 27:541-547.
106. Baloglu E., Ay Senyigit Z., Karavana S.Y., Vetter A., Metin D.Y., Hilmioglu Polat S., Guneri T., Bernkop-Schnurch A. 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. 2011, 59:952-958.
107. Wang L., Tang X. A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: design, in vitro and 'in vivo' evaluation. Int. J. Pharm. 2008, 350:181-187.
108. Hombach J., Palmberger T.F., Bernkop-Schnurch A. Development and in vitro evaluation of a mucoadhesive vaginal delivery system for nystatin. J. Pharm. Sci. 2009, 98:555-564.
109. Perioli L., Ambrogi V., Venezia L., Pagano C., Ricci M., Rossi C. Chitosan and a modified chitosan as agents to improve performances of mucoadhesive vaginal gels. Colloids Surf. B: Biointerfaces 2008, 66:141-145.
110. Perioli L., Ambrogi V., Pagano C., Scuota S., Rossi C. FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration. Int. J. Pharm. 2009, 377:120-127.
111. Voorspoels J., Casteels M., Remon J.P., Temmerman M. Local treatment of bacterial vaginosis with a bioadhesive metronidazole tablet. Eur. J. Obstet. Gynecol. Reprod. Biol. 2002, 105:64-66.
112. Abruzzo A., Bigucci F., Cerchiara T., Saladini B., Gallucci M.C., Cruciani F., Vitali B., Luppi B. Chitosan/alginate complexes for vaginal delivery of chlorhexidine digluconate. Carbohydr. Polym. 2013, 91:651-658.
113. Bigucci F., Angela A., Vitali B., Saladini B., Cerchiara T., Gallucci M.C., Luppi B. Vaginal inserts based on chitosan and carboxymethylcellulose complexes for local delivery of chlorhexidine: preparation, characterization and antimicrobial activity. Int. J. Pharm. 2014, 478:456-463.
114. Perioli L., Ambrogi V., Venezia L., Giovagnoli S., Pagano C., Rossi C. Formulation studies of benzydamine mucoadhesive formulations for vaginal administration. Drug Dev. Ind. Pharm. 2009, 35:769-779.
115. Wilson J. Managing recurrent bacterial vaginosis. Sex. Transm. Infect. 2004, 80:8-11.
116. Donders G.G., Zodzika J., Rezeberga D. Treatment of bacterial vaginosis: what we have and what we miss. Expert. Opin. Pharmacother. 2014, 15:645-657.
117. Robinson J.R., Bologna W.J. Vaginal and reproductive system treatments using a bioadhesive polymer. J. Control. Release 1994, 28:87-94.
118. Milani M., Molteni B., Silvani I. Effect on vaginal pH of a polycarbophil vaginal gel compared with an acidic douche in women with suspected bacterial vaginosis: a randomized, controlled study. Curr. Ther. Res. Clin. Exp. 2000, 2000:781-788.
119. Fiorilli A., Molteni B., Milani M. Successful treatment of bacterial vaginosis with a policarbophil-carbopol acidic vaginal gel: results from a randomised double-blind, placebo-controlled trial. Eur. J. Obstet. Gynecol. Reprod. Biol. 2005, 120:202-205.
120. Garg S., Anderson R.A., Chany C.J., Waller D.P., Diao X.H., Vermani K., Zaneveld L.J. Properties of a new acid-buffering bioadhesive vaginal formulation (ACIDFORM). Contraception 2001, 64:67-75.
121. Bayer L.L., Jensen J.T. ACIDFORM: a review of the evidence. Contraception 2014, 90:11-18.
122. Simoes J.A., Bahamondes L.G., Camargo R.P., Alves V.M., Zaneveld L.J., Waller D.P., Schwartz J., Callahan M.M., Mauck C.K. A pilot clinical trial comparing an acid-buffering formulation (ACIDFORM gel) with metronidazole gel for the treatment of symptomatic bacterial vaginosis. Br. J. Clin. Pharmacol. 2006, 61:211-217.
123. Singh V.K., Anis A., Banerjee I., Pramanik K., Bhattacharya M.K., Pal K. Preparation and characterization of novel carbopol based bigels for topical delivery of metronidazole for the treatment of bacterial vaginosis. Mater. Sci. Eng. C 2014, 44:151-158.
124. Baloglu E., Senyigit Z.A., Karavana S.Y., Bernkop-Schnurch A. Strategies to prolong the intravaginal residence time of drug delivery systems. J. Pharm. Pharm. Sci. 2009, 12:312-336.
125. Andersch B., Forssman L., Lincoln K., Torstensson P. Treatment of bacterial vaginosis with an acid cream: a comparison between the effect of lactate-gel and metronidazole. Gynecol. Obstet. Investig. 1986, 21:19-25.
126. Petersen E.E., Genet M., Caserini M., Palmieri R. Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial. Arzneimittelforschung 2011, 61:260-265.
127. Krasnopolsky V.N., Prilepskaya V.N., Polatti F., Zarochentseva N.V., Bayramova G.R., Caserini M., Palmieri R. Efficacy of vitamin C vaginal tablets as prophylaxis for recurrent bacterial vaginosis: a randomised, double-blind, placebo-controlled clinical trial. J. Clin. Med. Res. 2013, 5:309-315.
128. Abbaspoor Z., Fateme G., Abbaspoor M. Comparison of the effectiveness of vitamin C vaginal tablet with metronidazole vaginal gel in the treatment of bacterial vaginosis. Afr. J. Pharm. Pharmacol. 2010, 4:484-489.
129. Holley R.L., Richter H.E., Varner R.E., Pair L., Schwebke J.R. A randomized, double-blind clinical trial of vaginal acidification versus placebo for the treatment of symptomatic bacterial vaginosis. Sex. Transm. Dis. 2004, 31:236-238.
130. Boeke A.J., Dekker J.H., van Eijk J.T., Kostense P.J., Bezemer P.D. Effect of lactic acid suppositories compared with oral metronidazole and placebo in bacterial vaginosis: a randomised clinical trial. Genitourin. Med. 1993, 69:388-392.
131. Bonferoni M.C., Giunchedi P., Scalia S., Rossi S., Sandri G., Caramella C. Chitosan gels for the vaginal delivery of lactic acid: relevance of formulation parameters to mucoadhesion and release mechanisms. AAPS PharmSciTech 2006, 7:104.
132. Sandri G., Rossi S., Ferrari F., Bonferoni M.C., Muzzarelli C., Caramella C. Assessment of chitosan derivatives as buccal and vaginal penetration enhancers. Eur. J. Pharm. Sci. 2004, 21:351-359.
133. Dodane V., Amin Khan M., Merwin J.R. Effect of chitosan on epithelial permeability and structure. Int. J. Pharm. 1999, 182:21-32.
134. Chopra S., Mahdi S., Kaur J., Iqbal Z., Talegaonkar S., Ahmad F.J. Advances and potential applications of chitosan derivatives as mucoadhesive biomaterials in modern drug delivery. J. Pharm. Pharmacol. 2006, 58:1021-1032.
135. Palmeira-de-Oliveira A., Ribeiro M.P., Palmeira-de-Oliveira R., Gaspar C., Costa-de-Oliveira S., Correia I.J., Pina Vaz C., Martinez-de-Oliveira J., Queiroz J.A., Rodrigues A.G. Anti-Candida activity of a chitosan hydrogel: mechanism of action and cytotoxicity profile. Gynecol. Obstet. Investig. 2010, 70:322-327.
136. Seyfarth F., Schliemann S., Elsner P., Hipler U.C. Antifungal effect of high- and low-molecular-weight chitosan hydrochloride, carboxymethyl chitosan, chitosan oligosaccharide and N-acetyl-d-glucosamine against Candida albicans, Candida krusei and Candida glabrata. Int. J. Pharm. 2008, 353:139-148.
137. Rabea E.I., Badawy M.E., Stevens C.V., Smagghe G., Steurbaut W. Chitosan as antimicrobial agent: applications and mode of action. Biomacromolecules 2003, 4:1457-1465.
138. Knapczyk J., Macura A.B., Pawlik B. Simple tests demonstrating the antimycotic effect of chitosan. Int. J. Pharm. 1992, 80:33-38.
139. Palmeira-de-Oliveira A., Palmeira-de-Oliveira R., Gaspar C., Salgueiro L., Cavaleiro C., Martinez-de-Oliveira J., Queiroz J.A., Rodrigues A.G. Association of Thymbra capitata essential oil and chitosan (TCCH hydrogel): a putative therapeutic tool for the treatment of vulvovaginal candidosis. Flavour Fragr. J. 2013, 28:354-359.
140. Kandimalla K.K., Borden E., Omtri R.S., Boyapati S.P., Smith M., Lebby K., Mulpuru M., Gadde M. Ability of chitosan gels to disrupt bacterial biofilms and their applications in the treatment of bacterial vaginosis. J. Pharm. Sci. 2013, 102:2096-2101.
141. Silva-Dias A., Palmeira-de-Oliveira A., Miranda I.M., Branco J., Cobrado L., Monteiro-Soares M., Queiroz J.A., Pina-Vaz C., Rodrigues A.G. Anti-biofilm activity of low-molecular weight chitosan hydrogel against Candida species. Med. Microbiol. Immunol. 2014, 203:25-33.
142. Verstraelen H., Verhelst R., Roelens K., Temmerman M. Antiseptics and disinfectants for the treatment of bacterial vaginosis: a systematic review. BMC Infect. Dis. 2012, 12:148.
143. Frey Tirri B. Antimicrobial topical agents used in the vagina. Curr. Probl. Dermatol. 2011, 40:36-47.
144. Molteni B., D'Antuono A., Bandini P., Sintini G., Barcellona E., Agnello A., Milani M. Efficacy and tolerability of a new chlorhexidine-based vaginal gel in vaginal infections. Curr. Med. Res. Opin. 2004, 20:849-853.
145. Mehta S., Verstraelen H., Vandaele L., Mehuys E., Remon J.P., Vervaet C. Vaginal distribution and retention of tablets comprising starch-based multiparticulates: evaluation by colposcopy. Drug Dev. Ind. Pharm. 2013, 39:1944-1950.
146. Machado R.M., Palmeira-de-Oliveira A., Martinez-De-Oliveira J., Palmeira-de-Oliveira R. Vaginal films for drug delivery. J. Pharm. Sci. 2013, 102:2069-2081.
147. Rohan L.C., Sassi A.B. Vaginal drug delivery systems for HIV prevention. AAPS J. 2009, 11:78-87.
148. Dobaria N.B., Badhan A.C., Mashru R.C. A novel itraconazole bioadhesive film for vaginal delivery: design, optimization, and physicodynamic characterization. AAPS PharmSciTech 2009, 10:951-959.
149. Dobaria N., Mashru R. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clindamycin phosphate. Pharm. Dev. Technol. 2010, 15:405-414.
150. Kumar L., Reddy M.S., Shirodkar R.K., Pai G.K., Krishna V.T., Verma R. Preparation and characterisation of fluconazole vaginal films for the treatment of vaginal candidiasis. Indian J. Pharm. Sci. 2013, 75:585-590.
151. Gupta K.M., Barnes S.R., Tangaro R.A., Roberts M.C., Owen D.H., Katz D.F., Kiser P.F. Temperature and pH sensitive hydrogels: an approach towards smart semen-triggered vaginal microbicidal vehicles. J. Pharm. Sci. 2007, 96:670-681.
152. Zhang T., Sturgis T.F., Youan B.B. pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission. Eur. J. Pharm. Biopharm. 2011, 79:526-536.
153. Escobar-Chavez J.J., Lopez-Cervantes M., Naik A., Kalia Y.N., Quintanar-Guerrero D., Ganem-Quintanar A. Applications of thermo-reversible pluronic F-127 gels in pharmaceutical formulations. J. Pharm. Pharm. Sci. 2006, 9:339-358.
154. Chang J.Y., Oh Y.K., Kong H.S., Kim E.J., Jang D.D., Nam K.T., Kim C.K. Prolonged antifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis. J. Control. Release 2002, 82:39-50.
155. Bilensoy E., Rouf M.A., Vural I., Şen M., Hincal A.A. Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole:β-cyclodextrin complex. AAPS PharmSciTech 2006, 7.
156. Baloglu E., Karavana S.Y., Senyigit Z.A., Hilmioglu-Polat S., Metin D.Y., Zekioglu O., Guneri T., Jones D.S. In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evaluation. J. Pharm. Pharmacol. 2011, 63:1274-1282.
157. Karavana S.Y., Rençber S., Şenyiğit Z.A., Baloğlu E. A new in-situ gel formulation of itraconazole for vaginal administration. Pharmacol. Pharm. 2012, 3:417-426.
158. Hani U., Shivakamuar H.G. Development of miconazole nitrate thermosensitive bioadhesive vaginal gel for vaginal candidiasis. Am. J. Adv. Drug Deliv. 2013, 3:358-368.
159. Kang J.W., Davaa E., Kim Y.T., Park J.S. A new vaginal delivery system of amphotericin B: a dispersion of cationic liposomes in a thermosensitive gel. J. Drug Target. 2010, 18:637-644.
160. Ibrahim el-S.A., Ismail S., Fetih G., Shaaban O., Hassanein K., Abdellah N.H. Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application. Acta Pharma. 2012, 62:59-70.
161. Shaaban O.M., Fetih G.N., Abdellah N.H., Ismail S., Ibrahim M.A., Ibrahim el S.A. Pilot randomized trial for treatment of bacterial vaginosis using in situ forming metronidazole vaginal gel. J. Obstet. Gynaecol. Res. 2011, 37:874-881.
162. Ruel-Gariepy E., Leroux J.C. In situ-forming hydrogels-review of temperature-sensitive systems. Eur. J. Pharm. Biopharm. 2004, 58:409-426.
163. Rossi S., Ferrari F., Bonferoni M.C., Sandri G., Faccendini A., Puccio A., Caramella C. Comparison of poloxamer- and chitosan-based thermally sensitive gels for the treatment of vaginal mucositis. Drug Dev. Ind. Pharm. 2014, 40:352-360.
164. Ensign L.M., Cone R., Hanes J. Nanoparticle-based drug delivery to the vagina: a review. J. Control. Release 2014, 190:500-514.
165. Palmeira-de-Oliveira R., Palmeira-de-Oliveira A., Gaspar C., Silvestre S., Martinez-de-Oliveira J., Amaral M.H., Breitenfeld L. Sodium tripolyphosphate: an excipient with intrinsic in vitro anti-Candida activity. Int. J. Pharm. 2011, 421:130-134.
166. Esposito E., Ravani L., Contado C., Costenaro A., Drechsler M., Rossi D., Menegatti E., Grandini A., Cortesi R. Clotrimazole nanoparticle gel for mucosal administration. Mater. Sci. Eng. C 2013, 33:411-418.
167. Kohane D.S. Microparticles and nanoparticles for drug delivery. Biotechnol. Bioeng. 2007, 96:203-209.
168. Gupta N.V., Natasha S., Getyala A., Bhat R.S. Bioadhesive vaginal tablets containing spray dried microspheres loaded with clotrimazole for treatment of vaginal candidiasis. Acta Pharma. 2013, 63:359-372.
169. Albertini B., Passerini N., Di Sabatino M., Vitali B., Brigidi P., Rodriguez L. Polymer-lipid based mucoadhesive microspheres prepared by spray-congealing for the vaginal delivery of econazole nitrate. Eur. J. Pharm. Sci. 2009, 36:591-601.
170. Martin-Villena M.J., Fernandez-Campos F., Calpena-Campmany A.C., Bozal-de Febrer N., Ruiz-Martinez M.A., Clares-Naveros B. Novel microparticulate systems for the vaginal delivery of nystatin: development and characterization. Carbohydr. Polym. 2013, 94:1-11.
171. Santos S.S., Lorenzoni A., Ferreira L.M., Mattiazzi J., Adams A.I., Denardi L.B., Alves S.H., Schaffazick S.R., Cruz L. Clotrimazole-loaded Eudragit(R) RS100 nanocapsules: preparation, characterization and in vitro evaluation of antifungal activity against Candida species. Mater. Sci. Eng. C 2013, 33:1389-1394.
172. Duncan R., Izzo L. Dendrimer biocompatibility and toxicity. Adv. Drug Deliv. Rev. 2005, 57:2215-2237.
173. McGowan I., Gomez K., Bruder K., Febo I., Chen B.A., Richardson B.A., Husnik M., Livant E., Price C., Jacobson C., Team M.T.N.P. Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel) in sexually active young women (MTN-004). AIDS 2011, 25:1057-1064.
174. Price C.F., Tyssen D., Sonza S., Davie A., Evans S., Lewis G.R., Xia S., Spelman T., Hodsman P., Moench T.R., Humberstone A., Paull J.R., Tachedjian G. SPL7013 Gel (VivaGel(R)) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans. PLoS One 2011, 6.
175. Cunha A.R., Machado R.M., Palmeira-de-Oliveira A., Martinez-de-Oliveira J., das Neves J., Palmeira-de-Oliveira R. Characterization of commercially available vaginal lubricants: a safety perspective. Pharmaceutics 2014, 6:530-542.
176. Allen T.M., Cullis P.R. Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev. 2013, 65:36-48.
177. Pavelic Z., Skalko-Basnet N., Jalsenjak I. Liposomes containing drugs for treatment of vaginal infections. Eur. J. Pharm. Sci. 1999, 8:345-351.
178. Joraholmen M.W., Vanic Z., Tho I., Skalko-Basnet N. Chitosan-coated liposomes for topical vaginal therapy: assuring localized drug effect. Int. J. Pharm. 2014, 472:94-101.
179. Ning M., Guo Y., Pan H., Chen X., Gu Z. Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole. Drug Dev. Ind. Pharm. 2005, 31:375-383.
180. Vanic Z., Hafner A., Bego M., Skalko-Basnet N. Characterization of various deformable liposomes with metronidazole. Drug Dev. Ind. Pharm. 2013, 39:481-488.
181. Pavelic Z., Skalko-Basnet N., Jalsenjak I. Characterisation and in vitro evaluation of bioadhesive liposome gels for local therapy of vaginitis. Int. J. Pharm. 2005, 301:140-148.
182. Karimunnisa S., Atmaram P. Mucoadhesive nanoliposomal formulation for vaginal delivery of an antifungal. Drug Dev. Ind. Pharm. 2013, 39:1328-1337.
183. Bernkop-Schnurch A., Dunnhaupt S. Chitosan-based drug delivery systems. Eur. J. Pharm. Biopharm. 2012, 81:463-469.
184. Sharma R., Garg T., Goyal A.K., Rath G. Development, optimization and evaluation of polymeric electrospun nanofiber: a tool for local delivery of fluconazole for management of vaginal candidiasis. Artif. Cells Nanomed. Biotechnol. 2014, 1-8.
185. Hettiarachchi N., Ashbee H.R., Wilson J.D. Prevalence and management of non-albicans vaginal candidiasis. Sex. Transm. Infect. 2010, 86:99-100.
186. Palmeira-de-Oliveira A., Ramos A.R., Gaspar C., Palmeira-de-Oliveira R., Gouveia P., Martinez-de-Oliveira J. In vitro anti-Candida activity of lidocaine and nitroglycerin: alone and combined. Infect. Dis. Obstet. Gynecol. 2012, 2012:727248.
187. Lass-Florl C., Dierich M.P., Fuchs D., Semenitz E., Ledochowski M. Antifungal activity against Candida species of the selective serotonin-reuptake inhibitor, sertraline. Clin. Infect. Dis. 2001, 33:E135-E136.
188. Oliveira A.S., Gaspar C.A., Palmeira-de-Oliveira R., Martinez-de-Oliveira J., Palmeira-de-Oliveira A. Anti-Candida activity of fluoxetine alone and combined with fluconazole: a synergistic action against fluconazole-resistant strains. Antimicrob. Agents Chemother. 2014, 58:4224-4226.
189. Gomes-de-Elvas A.R., Palmeira-de-Oliveira A., Gaspar C., Gouveia P., Palmeira-de-Oliveira R., Pina-Vaz C., Rodrigues A.G., Martinez-de-Oliveira J. In vitro assessment of gentian violet anti-Candida activity. Gynecol. Obstet. Investig. 2012, 74:120-124.
190. Braga-Silva L.A., Santos A.L. Aspartic protease inhibitors as potential anti-Candida albicans drugs: impacts on fungal biology, virulence and pathogenesis. Curr. Med. Chem. 2011, 18:2401-2419.
191. De Bernardis F., Arancia S., Tringali G., Greco M.C., Ragazzoni E., Calugi C., Trabocchi A., Sandini S., Graziani S., Cauda R., Cassone A., Guarna A., Navarra P. Evaluation of efficacy, pharmacokinetics and tolerability of peptidomimetic aspartic proteinase inhibitors as cream formulation in experimental vaginal candidiasis. J. Pharm. Pharmacol. 2014, 66:1094-1101.
192. Weissenbacher E.R., Donders G., Unzeitig V., Martinez de Tejada B., Gerber S., Halaska M., Spacek J., Fluomizin Study G. A comparison of dequalinium chloride vaginal tablets (Fluomizin(R)) and clindamycin vaginal cream in the treatment of bacterial vaginosis: a single-blind, randomized clinical trial of efficacy and safety. Gynecol. Obstet. Investig. 2012, 73:8-15.
193. Donders G.G., Guaschino S., Peters K., Tacchi R., Lauro V., Group V.S. A multicenter, double-blind, randomized, placebo-controlled study of rifaximin for the treatment of bacterial vaginosis. Int. J. Gynaecol. Obstet. 2013, 120:131-136.
194. Van Kessel K., Assefi N., Marrazzo J., Eckert L. Common complementary and alternative therapies for yeast vaginitis and bacterial vaginosis: a systematic review. Obstet. Gynecol. Surv. 2003, 58:351-358.
195. Njamen D., Mvondo M.A., Djiogue S., Ketcha Wanda G.J., Magne Nde C.B., Vollmer G. Phytotherapy and women's reproductive health: the Cameroonian perspective. Planta Med. 2013, 79:600-611.
196. Jordan S.A., Cunningham D.G., Marles R.J. Assessment of herbal medicinal products: challenges, and opportunities to increase the knowledge base for safety assessment. Toxicol. Appl. Pharmacol. 2010, 243:198-216.
197. Palmeira-de-Oliveira R., Duarte P., Palmeira-de-Oliveira A., das Neves J., Amaral M.H., Breitenfeld L., Martinez-de-Oliveira J. What do Portuguese women prefer regarding vaginal products? Results from a cross-sectional web-based survey. Pharmaceutics 2014, 6:543-556.
198. Palmeira-de-Oliveira A., Salgueiro L., Palmeira-de-Oliveira R., Martinez-de-Oliveira J., Pina-Vaz C., Queiroz J.A., Rodrigues A.G. Anti-Candida activity of essential oils. Mini Rev. Med. Chem. 2009, 9:1292-1305.
199. Hammer K.A., Carson C.F., Riley T.V. Antimicrobial activity of essential oils and other plant extracts. J. Appl. Microbiol. 1999, 86:985-990.
200. Palmeira-de-Oliveira A., Silva B.M., Palmeira-de-Oliveira R., Martinez-de-Oliveira J., Salgueiro L. Are plant extracts a potential therapeutic approach for genital infections?. Curr. Med. Chem. 2013, 20:2914-2928.
201. Koroch A.R., Juliani H.R., Zygadlo J.A. Bioactivity of essential oils and their components. Flavours and Fragrances: Chemistry 2007, 87-115. Bioprocessing and Sustainability. Springer, Berlin. R.G. Berger (Ed.).
202. Hammer K.A., Carson C.F., Riley T.V. In-vitro activity of essential oils, in particular Melaleuca alternifolia (tea tree) oil and tea tree oil products, against Candida spp. J. Antimicrob. Chemother. 1998, 42:591-595.
203. Hammer K.A., Carson C.F., Riley T.V. In vitro susceptibilities of lactobacilli and organisms associated with bacterial vaginosis to Melaleuca alternifolia (tea tree) oil. Antimicrob. Agents Chemother. 1999, 43:196.
204. Viollon C., Mandin D., Chaumont J. Activites antagonistes, in vitro, of some essential oils and natural volatile compounds vis a vis the growth of Trichomonas vaginalis. Fitoterapia 1996, 67:279-281.
205. Farag R.S., Shalaby A.S., El-Baroty G.A., Ibrahim N.A., Ali M.A., Hassan E.M. Chemical and biological evaluation of the essential oils of different Melaleuca species. Phytother. Res. 2004, 18:30-35.
206. Oliva B., Piccirilli E., Ceddia T., Pontieri E., Aureli P., Ferrini A.M. Antimycotic activity of Melaleuca alternifolia essential oil and its major components. Lett. Appl. Microbiol. 2003, 37:185-187.
207. Hammer K.A., Carson C.F., Riley T.V. Antifungal effects of Melaleuca alternifolia (tea tree) oil and its components on Candida albicans, Candida glabrata and Saccharomyces cerevisiae. J. Antimicrob. Chemother. 2004, 53:1081-1085.
208. Reichling J., Landvatter U., Wagner H., Kostka K.H., Schaefer U.F. In vitro studies on release and human skin permeation of Australian tea tree oil (TTO) from topical formulations. Eur. J. Pharm. Biopharm. 2006, 64:222-228.
209. Herman A., Herman A.P. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: a review. J. Pharm. Pharmacol. 2015, 67:473-485.
210. Cosentino S., Tuberoso C.I., Pisano B., Satta M., Mascia V., Arzedi E., Palmas F. In-vitro antimicrobial activity and chemical composition of Sardinian Thymus essential oils. Lett. Appl. Microbiol. 1999, 29:130-135.
211. Giordani R., Regli P., Kaloustian J., Mikail C., Abou L., Portugal H. Antifungal effect of various essential oils against Candida albicans. Potentiation of antifungal action of amphotericin B by essential oil from Thymus vulgaris. Phytother. Res. 2004, 18:990-995.
212. Pina-Vaz C., Goncalves Rodrigues A., Pinto E., Costa-de-Oliveira S., Tavares C., Salgueiro L., Cavaleiro C., Goncalves M.J., Martinez-de-Oliveira J. Antifungal activity of Thymus oils and their major compounds. J. Eur. Acad. Dermatol. Venereol. 2004, 18:73-78.
213. Palmeira-de-Oliveira A., Gaspar C., Palmeira-de-Oliveira R., Silva-Dias A., Salgueiro L., Cavaleiro C., Pina-Vaz C., Martinez-de-Oliveira J., Queiroz J.A., Rodrigues A.G. The anti-Candida activity of Thymbra capitata essential oil: effect upon pre-formed biofilm. J. Ethnopharmacol. 2012, 140:379-383.
214. das Neves J., Pinto E., Amaral M.H., Bahia M.F. Antifungal activity of a gel containing Thymus vulgaris essential oil against Candida species commonly involved in vulvovaginal candidosis. Pharm. Biol. 2009, 47:151-153.
215. Khosravi A.R., Eslami A.R., Shokri H., Kashanian M. Zataria multiflora cream for the treatment of acute vaginal candidiasis. Int. J. Gynaecol. Obstet. 2008, 101:201-202.
216. Simbar M., Azarbad Z., Mojab F., Majd H.A. A comparative study of the therapeutic effects of the Zataria multiflora vaginal cream and metronidazole vaginal gel on bacterial vaginosis. Phytomedicine 2008, 15:1025-1031.
217. Sharma R.S., Mathur A.K., Chandhiok N., Datey S., Saxena N.C., Gopalan S., Sharma S., Mittal S., Sehgal R., Sumandal B.K., Chanda A., Salvi V., Mutalik N., Coyaji K.J., Gibsson A., Hazari K., Kalgutkar S., Talwar G.P. Phase II clinical trial with Praneem polyherbal tablets for assessment of their efficacy in symptomatic women with abnormal vaginal discharge (an ICMR task force study). Trans. R. Soc. Trop. Med. Hyg. 2009, 103:167-172.
218. Nyirjesy P., Robinson J., Mathew L., Lev-Sagie A., Reyes I., Culhane J.F. Alternative therapies in women with chronic vaginitis. Obstet. Gynecol. 2011, 117:856-861.
219. Shams-Ghahfarokhi M., Shokoohamiri M.R., Amirrajab N., Moghadasi B., Ghajari A., Zeini F., Sadeghi G., Razzaghi-Abyaneh M. In vitro antifungal activities of Allium cepa, Allium sativum and ketoconazole against some pathogenic yeasts and dermatophytes. Fitoterapia 2006, 77:321-323.
220. Bahadoran P., Rokni F.K., Fahami F. Investigating the therapeutic effect of vaginal cream containing garlic and thyme compared to clotrimazole cream for the treatment of mycotic vaginitis. Iran. J. Nurs. Midwifery Res. 2010, 15:343-349.
221. FAO/WHO Report of a Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk With Live Lactic Acid Bacteria. American Córdoba Park Hotel, Córdoba, Argentina, 1-4 October 2001.
222. Shanahan F., Stanton C., Ross P., Hill C. Pharmabiotics: bioactives from mining host-microbe-dietary interactions. Funct. Food Rev. 2009, 1:1-6.
223. Boris S., Barbes C. Role played by lactobacilli in controlling the population of vaginal pathogens. Microbes Infect. 2000, 2:543-546.
224. Nader-Macias M.E., Silva-Ruiz C., Ocana V., Juarez Tomas M.S. Advances in the knowledge and clinical applications of lactic acid bacteria as probiotics in the urogenital tract. Curr. Women's Health Rev. 2008, 4:240-257.
225. Falagas M.E., Betsi G.I., Athanasiou S. Probiotics for prevention of recurrent vulvovaginal candidiasis: a review. J. Antimicrob. Chemother. 2006, 58:266-272.
226. Wagner R.D., Johnson S.J. Probiotic lactobacillus and estrogen effects on vaginal epithelial gene expression responses to Candida albicans. J. Biomed. Sci. 2012, 19:58.
227. Maggi L., Mastromarino P., Macchia S., Brigidi P., Pirovano F., Matteuzzi D., Conte U. Technological and biological evaluation of tablets containing different strains of lactobacilli for vaginal administration. Eur. J. Pharm. Biopharm. 2000, 50:389-395.
228. Gunawardana M., Mullen M., Yoo J., Webster P., Moss J.A., Baum M.M. Sustained delivery of commensal bacteria from pod-intravaginal rings. Antimicrob. Agents Chemother. 2014, 58:2262-2267.
229. Barrons R., Tassone D. Use of Lactobacillus probiotics for bacterial genitourinary infections in women: a review. Clin. Ther. 2008, 30:453-468.
230. Pirotta M., Gunn J., Chondros P., Grover S., O'Malley P., Hurley S., Garland S. Effect of lactobacillus in preventing post-antibiotic vulvovaginal candidiasis: a randomised controlled trial. BMJ 2004, 329:548.
231. Kovachev S.M., Vatcheva-Dobrevska R.S. Local probiotic therapy for vaginal Candida albicans infections. Probiotics Antimicrob. Proteins 2015, 7:38-44.
232. De Seta F., Parazzini F., De Leo R., Banco R., Maso G.P., De Santo D., Sartore A., Stabile G., Inglese S., Tonon M., Restaino S. Lactobacillus plantarum P17630 for preventing Candida vaginitis recurrence: a retrospective comparative study. Eur. J. Obstet. Gynecol. Reprod. Biol. 2014, 182:136-139.
233. Donders G.G., Van Bulck B., Van de Walle P., Kaiser R.R., Pohlig G., Gonser S., Graf F. Effect of lyophilized lactobacilli and 0.03mg estriol (Gynoflor(R)) on vaginitis and vaginosis with disrupted vaginal microflora: a multicenter, randomized, single-blind, active-controlled pilot study. Gynecol. Obstet. Investig. 2010, 70:264-272.
234. Vicariotto F., Del Piano M., Mogna L., Mogna G. Effectiveness of the association of 2 probiotic strains formulated in a slow release vaginal product, in women affected by vulvovaginal candidiasis: a pilot study. J. Clin. Gastroenterol. 2012, 46(Suppl.):S73-S80.
235. Rousseau V., Lepargneur J.P., Roques C., Remaud-Simeon M., Paul F. Prebiotic effects of oligosaccharides on selected vaginal lactobacilli and pathogenic microorganisms. Anaerobe 2005, 11:145-153.
236. Coste I., Judlin P., Lepargneur J.P., Bou-Antoun S. Safety and efficacy of an intravaginal prebiotic gel in the prevention of recurrent bacterial vaginosis: a randomized double-blind study. Obstet. Gynecol. Int. 2012, 2012:147867.
237. Reid G., Soboh F., Bruce A.W., Mittelman M. Effect of nutrient composition on the in vitro growth of urogenital lactobacilli and uropathogens. Can. J. Microbiol. 1998, 44:866-871.