Nanoparticle-based drug delivery to the vagina: A review

Journal of Controlled Release

Volumn 190, Issue , 2014, Pages 500-514

  Ensign, Laura M ^a   Cone, Richard ^a   Hanes, Justin ^a,b,c  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Johns Hopkins University   (United States)

^c Johns Hopkins University   (United States)

Author keywords

Cervical cancer; HIV PrEP; Microbicides; Mucosal vaccines; Sexually transmitted infections

Indexed keywords

DISEASES; DRUG DELIVERY; DRUG DOSAGE; DRUG PRODUCTS; LIPOSOMES; NANOPARTICLES;

CERVICAL CANCERS; HIV PREP; MICROBICIDES; MUCOSAL VACCINE; SEXUALLY TRANSMITTED INFECTIONS;

NANOPARTICLES; DRUG DOSAGE;

DENDRIMER; HORMONE; INORGANIC NANOPARTICLE; LIPOSOME; NANOPARTICLE; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; DRUG CARRIER; POLYMER;

BACTERIAL INFECTION; CLINICAL TRIAL (TOPIC); DRUG DELIVERY SYSTEM; FEMALE GENITAL TRACT CANCER; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; INFECTION PREVENTION; INTRAVAGINAL DRUG ADMINISTRATION; MUCUS; MYCOSIS; NONHUMAN; PHYSIOLOGY; POLYMERIZATION; PRIORITY JOURNAL; REVIEW; VAGINA; VAGINA FLORA; VAGINA MUCOSA; ANIMAL; CHEMISTRY; FEMALE; MICROBIOLOGY; PATHOLOGY; SEXUALLY TRANSMITTED DISEASES; UTERINE CERVICAL NEOPLASMS; MICROFLORA; SEXUALLY TRANSMITTED DISEASE; TREATMENT OUTCOME; UTERINE CERVIX CANCER;

ADMINISTRATION, INTRAVAGINAL; ANIMALS; ANTI-INFECTIVE AGENTS; DRUG CARRIERS; FEMALE; HUMANS; LIPOSOMES; NANOPARTICLES; POLYMERS; SEXUALLY TRANSMITTED DISEASES; UTERINE CERVICAL NEOPLASMS; VAGINA;

EID: 84906781659     PISSN: 01683659     EISSN: 18734995     Source Type: Journal    
DOI: 10.1016/j.jconrel.2014.04.033     Document Type: Review

References (152)

1. V.M. Ndesendo, V. Pillay, Y.E. Choonara, E. Buchmann, D.N. Bayever, and L.C. Meyer A review of current intravaginal drug delivery approaches employed for the prophylaxis of HIV/AIDS and prevention of sexually transmitted infections AAPS PharmSciTech 9 2008 505 520
2. V. Ashok, R.M. Kumar, D. Murali, and A. Chatterjee A review on vaginal route as a systemic drug delivery Crit. Rev. Pharm. Sci. 1 2012 1 19
3. N.J. Alexander, E. Baker, M. Kaptein, U. Karck, L. Miller, and E. Zampaglione Why consider vaginal drug administration? Fertil. Steril. 82 2004 1 12 (Pubitemid 38968766)
4. S. Garg Vaginal microbicide formulations workshop Pharm. Sci. Technol. Today 1 1998 369
5. E. Odeblad Intracavitary circulation of aqueous material in the human vagina Acta Obstet. Gynecol. Scand. 43 1964 360 368
6. P.B. Pendergrass, M.W. Belovicz, and C.A. Reeves Surface area of the human vagina as measured from vinyl polysiloxane casts Gynecol. Obstet. Investig. 55 2003 110 113 (Pubitemid 36667680)
7. K.T. Barnhart, E.S. Pretorius, K. Timbers, D. Shera, M. Shabbout, and D. Malamud In vivo distribution of a vaginal gel: MRI evaluation of the effects of gel volume, time and simulated intercourse Contraception 70 2004 498 505 (Pubitemid 39488208)
8. P. Mirmonsef, D. Gilbert, R.S. Veazey, J. Wang, S.R. Kendrick, and G.T. Spear A comparison of lower genital tract glycogen and lactic acid levels in women and macaques: implications for HIV and SIV susceptibility AIDS Res. Hum. Retrovir. 28 2012 76 81
9. M.A. Sande, and O. Zak Handbook of Animal Models of Infection: Experimental Models in Antimicrobial Chemotherapy 1999 Elsevier Science
10. E.R. Boskey, K.M. Telsch, K.J. Whaley, T.R. Moench, and R.A. Cone Acid production by vaginal flora in vitro is consistent with the rate and extent of vaginal acidification Infect. Immun. 67 1999 5170 5175 (Pubitemid 29455288)
11. C.A. Fox, S.J. Meldrum, and B.W. Watson Continuous measurement by radio-telemetry of vaginal pH during human coitus J. Reprod. Fertil. 33 1973 69 75
12. R.A. Cone Barrier properties of mucus Adv. Drug Deliv. Rev. 61 2009 75 85
13. E. Odeblad The functional structure of human cervical mucus Acta Obstet. Gynecol. Scand. 47 1968 57 79
14. D.F. Katz, and E.N. Dunmire Cervical-mucus - problems and opportunities for drug-delivery via the vagina and cervix Adv. Drug Deliv. Rev. 11 1993 385 401 (Pubitemid 23302853)
15. S.K. Lai, Y.Y. Wang, K. Hida, R. Cone, and J. Hanes Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses Proc. Natl. Acad. Sci. U. S. A. 107 2010 598 603
16. F. Acarturk Mucoadhesive vaginal drug delivery systems Recent Pat. Drug Deliv. Formul. 3 2009 193 205
17. S.K. Lai, D.E. O'Hanlon, S. Harrold, S.T. Man, Y.Y. Wang, R. Cone, and J. Hanes Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus Proc. Natl. Acad. Sci. U. S. A. 104 2007 1482 1487 (Pubitemid 46214616)
18. S.S. Olmsted, J.L. Padgett, A.I. Yudin, K.J. Whaley, T.R. Moench, and R.A. Cone Diffusion of macromolecules and virus-like particles in human cervical mucus Biophys. J. 81 2001 1930 1937 (Pubitemid 32917145)
19. J. das Neves, M. Amiji, and B. Sarmento Mucoadhesive nanosystems for vaginal microbicide development: friend or foe? Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 3 2011 389 399
20. L.M. Ensign, B.C. Tang, Y.Y. Wang, T.A. Tse, T. Hoen, R. Cone, and J. Hanes Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus Sci. Transl. Med. 4 2012 138ra179
21. M. Yang, T. Yu, Y.Y. Wang, S.K. Lai, Q. Zeng, B. Miao, B.C. Tang, B.W. Simons, L.M. Ensign, G. Liu, K.W. Chan, C.Y. Juang, O. Mert, J. Wood, J. Fu, M.T. McMahon, T.C. Wu, C.F. Hung, and J. Hanes Vaginal Delivery of Paclitaxel via Nanoparticles with Non-Mucoadhesive Surfaces Suppresses Cervical Tumor Growth 2013 Advanced Healthcare Materials
22. Y. Kumamoto, and A. Iwasaki Unique features of antiviral immune system of the vaginal mucosa Curr. Opin. Immunol. 24 2012 411 416
23. K.A. Woodrow, K.M. Bennett, and D.D. Lo Mucosal vaccine design and delivery Annu. Rev. Biomed. Eng. 14 2012 17 46
24. C.R. Wira, J.V. Fahey, M. Ghosh, M.V. Patel, D.K. Hickey, and D.O. Ochiel Sex hormone regulation of innate immunity in the female reproductive tract: the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens Am. J. Reprod. Immunol. 63 2010 544 565
25. C.R. Wira, J.V. Fahey, C.L. Sentman, P.A. Pioli, and L. Shen Innate and adaptive immunity in female genital tract: cellular responses and interactions Immunol. Rev. 206 2005 306 335 (Pubitemid 41105178)
26. C.R. Wira, M.V. Patel, M. Ghosh, L. Mukura, and J.V. Fahey Innate immunity in the human female reproductive tract: endocrine regulation of endogenous antimicrobial protection against HIV and other sexually transmitted infections Am. J. Reprod. Immunol. 65 2011 196 211
27. C.S. Dezzutti, E.R. Brown, B. Moncla, J. Russo, M. Cost, L. Wang, K. Uranker, R.P. Kunjara Na Ayudhya, K. Pryke, J. Pickett, M.A. Leblanc, and L.C. Rohan Is wetter better? An evaluation of over-the-counter personal lubricants for safety and anti-HIV-1 activity PLoS One 7 2012 e48328
28. T.R. Moench, R.J. Mumper, T.E. Hoen, M. Sun, and R.A. Cone Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse BMC Infect. Dis. 10 2010 331
29. Z. Hel, E. Stringer, and J. Mestecky Sex steroid hormones, hormonal contraception, and the immunobiology of human immunodeficiency virus-1 infection Endocr. Rev. 31 2010 79 97
30. Y.Y. Wang, A. Kannan, K.L. Nunn, M.A. Murphy, D.B. Subramani, T. Moench, R. Cone, and S.K. Lai IgG in cervicovaginal mucus traps HSV and prevents vaginal herpes infections Mucosal Immunol. 2014 10.1038/mi.2013.120
31. M.A. Arias, A. Loxley, C. Eatmon, G. Van Roey, D. Fairhurst, M. Mitchnick, P. Dash, T. Cole, F. Wegmann, Q. Sattentau, and R. Shattock Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen Vaccine 29 2011 1258 1269
32. A. Pattani, P.F. McKay, M.J. Garland, R.M. Curran, K. Migalska, C.M. Cassidy, R.K. Malcolm, R.J. Shattock, H.O. McCarthy, and R.F. Donnelly Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations J. Control. Release 162 2012 529 537
33. P.A. Anton, R.D. Cranston, A. Kashuba, C.W. Hendrix, N.N. Bumpus, N. Richardson-Harman, J. Elliott, L. Janocko, E. Khanukhova, R. Dennis, W.G. Cumberland, C. Ju, A. Carballo-Dieguez, C. Mauck, and I. McGowan RMP-02/MTN-006: a phase 1 rectal safety, acceptability, pharmacokinetic, and pharmacodynamic study of tenofovir 1% gel compared with oral tenofovir disoproxil fumarate AIDS Res. Hum. Retrovir. 28 2012 1412 1421
34. J. Nuttall, A. Kashuba, R. Wang, N. White, P. Allen, J. Roberts, and J. Romano Pharmacokinetics of tenofovir following intravaginal and intrarectal administration of tenofovir gel to rhesus macaques Antimicrob. Agents Chemother. 56 2012 103 109
35. A.A. Date, and C.J. Destache A review of nanotechnological approaches for the prophylaxis of HIV/AIDS Biomaterials 34 2013 6202 6228
36. R. Mallipeddi, and L.C. Rohan Nanoparticle-based vaginal drug delivery systems for HIV prevention Expert Opin. Drug Deliv. 7 2010 37 48
37. C.H. Hubscher, D.L. Brooks, and J.R. Johnson A quantitative method for assessing stages of the rat estrous cycle Biotech. Histochem. 80 2005 79 87 (Pubitemid 41403364)
38. X. Zhao, E. Deak, K. Soderberg, M. Linehan, D. Spezzano, J. Zhu, D.M. Knipe, and A. Iwasaki Vaginal submucosal dendritic cells, but not Langerhans cells, induce protective Th1 responses to herpes simplex virus-2 J. Exp. Med. 197 2003 153 162 (Pubitemid 36152310)
39. C. Kaushic, A.A. Ashkar, L.A. Reid, and K.L. Rosenthal Progesterone increases susceptibility and decreases immune responses to genital herpes infection J. Virol. 77 2003 4558 4565 (Pubitemid 36402805)
40. R.M. Brotman, M.A. Klebanoff, T.R. Nansel, W.W. Andrews, J.R. Schwebke, J. Zhang, K.F. Yu, J.M. Zenilman, and D.O. Scharfstein A longitudinal study of vaginal douching and bacterial vaginosis - a marginal structural modeling analysis Am. J. Epidemiol. 168 2008 188 196 (Pubitemid 351951592)
41. P.M. Gorbach, R.E. Weiss, E. Fuchs, R.A. Jeffries, M. Hezerah, S. Brown, A. Voskanian, E. Robbie, P. Anton, and R.D. Cranston The slippery slope: lubricant use and rectal sexually transmitted infections: a newly identified risk Sex. Transm. Dis. 39 2012 59 64
42. D.E. O'Hanlon, T.R. Moench, and R.A. Cone Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota PLoS One 8 2013 e80074
43. T.L. Cherpes, J.M. Marrazzo, L.A. Cosentino, L.A. Meyn, P.J. Murray, and S.L. Hillier Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis Sex. Transm. Infect. 84 2008 57 61 (Pubitemid 351195855)
44. A. Hemmerling, W. Harrison, A. Schroeder, J. Park, A. Korn, S. Shiboski, and C.R. Cohen Phase 1 dose-ranging safety trial of Lactobacillus crispatus CTV-05 for the prevention of bacterial vaginosis Sex. Transm. Dis. 36 2009 564 569
45. A.M. Briselden, B.J. Moncla, C.E. Stevens, and S.L. Hillier Sialidases (neuraminidases) in bacterial vaginosis and bacterial vaginosis-associated microflora J. Clin. Microbiol. 30 1992 663 666
46. S. Cauci, J.F. Culhane, M. Di Santolo, and K. McCollum Among pregnant women with bacterial vaginosis, the hydrolytic enzymes sialidase and prolidase are positively associated with interleukin-1 beta Am. J. Obstet. Gynecol. 198 2008
47. J.F. Culhane, P. Nyirjesy, K. McCollum, R.L. Goldenberg, S.E. Gelber, and S. Cauci Variation in vaginal immune parameters and microbial hydrolytic enzymes in bacterial vaginosis positive pregnant women with and without Mobiluncus species Am. J. Obstet. Gynecol. 195 2006 516 521 (Pubitemid 44142385)
48. H. Verstraelen, and A. Swidsinski The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment Curr. Opin. Infect. Dis. 26 2013 86 89
49. D.L. Patton, S.S. Thwin, A. Meier, T.M. Hooton, A.E. Stapleton, and D.A. Eschenbach 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 2000 967 973
50. A. Hussain, and F. Ahsan The vagina as a route for systemic drug delivery J. Control. Release 103 2005 301 313 (Pubitemid 40342532)
51. S.M. Smith, G.B. Baskin, and P.A. Marx Estrogen protects against vaginal transmission of simian immunodeficiency virus J. Infect. Dis. 182 2000 708 715
52. A.E. Gillgrass, S.A. Fernandez, K.L. Rosenthal, and C. Kaushic Estradiol regulates susceptibility following primary exposure to genital herpes simplex virus type 2, while progesterone induces inflammation J. Virol. 79 2005 3107 3116 (Pubitemid 40270589)
53. N. Chandra, A.R. Thurman, S. Anderson, T.D. Cunningham, N. Yousefieh, C. Mauck, and G.F. Doncel Depot medroxyprogesterone acetate increases immune cell numbers and activation markers in human vaginal mucosal tissues AIDS Res. Hum. Retrovir. 29 2013 592 601
54. G.S. Evans, D.F.C. Gibson, S.A. Roberts, T.M. Hind, and C.S. Potten Proliferative changes in the genital tissue of female mice during the estrous-cycle Cell Tissue Kinet. 23 1990 619 635
55. A.W. Asscher, C.H. De Boer, and C.J. Turner Cornification of the human vaginal epithelium J. Anat. 90 1956 547 552
56. B.G. Smith, and E.K. Brunner The structure of the human vaginal mucosa in relation to the menstrual cycle and to pregnancy Am. J. Anat. 54 1934 27 85
57. L.M. Ensign, A. Henning, C.S. Schneider, K. Maisel, Y.Y. Wang, M.D. Porosoff, R. Cone, and J. Hanes Ex vivo characterization of particle transport in mucus secretions coating freshly excised mucosal tissues Mol. Pharm. 10 2013 2176 2182
58. K.V. Khanna, K.J. Whaley, L. Zeitlin, T.R. Moench, K. Mehrazar, R.A. Cone, Z. Liao, J.E. Hildreth, T.E. Hoen, L. Shultz, and R.B. Markham Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent J. Clin. Invest. 109 2002 205 211 (Pubitemid 34083740)
59. M.J. Durrani, A. Kusai, N.F.H. Ho, J.L. Fox, and W.I. Higuchi Topical vaginal drug delivery in the guinea-pig. 1. Effect of estrous-cycle on the vaginal membrane-permeability of Vidarabine Int. J. Pharm. 24 1985 209 218 (Pubitemid 15062530)
60. T. Kanazawa, Y. Takashima, S. Hirayama, and H. Okada Effects of menstrual cycle on gene transfection through mouse vagina for DNA vaccine Int. J. Pharm. 360 2008 164 170
61. D. Palliser, D. Chowdhury, Q.Y. Wang, S.J. Lee, R.T. Bronson, D.M. Knipe, and J. Lieberman An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection Nature 439 2006 89 94 (Pubitemid 43053634)
62. S.Y. Wu, H.I. Chang, M. Burgess, and N.A. McMillan Vaginal delivery of siRNA using a novel PEGylated lipoplex-entrapped alginate scaffold system J. Control. Release 155 2011 418 426
63. R.A. Cone, T. Hoen, X. Wong, R. Abusuwwa, D.J. Anderson, and T.R. Moench Vaginal microbicides: detecting toxicities in vivo that paradoxically increase pathogen transmission BMC Infect. Dis. 6 2006 90
64. S.S. Wilson, N. Cheshenko, E. Fakioglu, P.M. Mesquita, M.J. Keller, and B.C. Herold Susceptibility to genital herpes as a biomarker predictive of increased HIV risk: expansion of a murine model of microbicide safety Antivir. Ther. 14 2009 1113 1124
65. M. Dawson, E. Krauland, D. Wirtz, and J. Hanes Transport of polymeric nanoparticle gene carriers in gastric mucus Biotechnol. Prog. 20 2004 851 857 (Pubitemid 38784024)
66. Y.Y. Wang, S.K. Lai, J.S. Suk, A. Pace, R. Cone, and J. Hanes Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that "slip" through the human mucus barrier Angew. Chem. 47 2008 9726 9729
67. S.K. Lai, Y.Y. Wang, R. Cone, D. Wirtz, and J. Hanes Altering mucus rheology to "solidify" human mucus at the nanoscale PLoS One 4 2009 e4294
68. Y. Cu, and W.M. Saltzman Controlled surface modification with poly(ethylene)glycol enhances diffusion of PLGA nanoparticles in human cervical mucus Mol. Pharm. 6 2009 173 181
69. B.C. Tang, M. Dawson, S.K. Lai, Y.Y. Wang, J.S. Suk, M. Yang, P. Zeitlin, M.P. Boyle, J. Fu, and J. Hanes Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier Proc. Natl. Acad. Sci. U. S. A. 106 2009 19268 19273
70. Y. Cu, C.J. Booth, and W.M. Saltzman In vivo distribution of surface-modified PLGA nanoparticles following intravaginal delivery J. Control. Release 156 2011 258 264
71. L.M. Ensign, T.E. Hoen, K. Maisel, R.A. Cone, and J.S. Hanes Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake Biomaterials 34 2013 6922 6929
72. M. Yang, S.K. Lai, Y.Y. Wang, W. Zhong, C. Happe, M. Zhang, J. Fu, and J. Hanes Biodegradable nanoparticles composed entirely of safe materials that rapidly penetrate human mucus Angew. Chem. 50 2011 2597 2600
73. Y. Wu, F. Navarro, A. Lal, E. Basar, R.K. Pandey, M. Manoharan, Y. Feng, S.J. Lee, J. Lieberman, and D. Palliser Durable protection from herpes simplex virus-2 transmission following intravaginal application of siRNAs targeting both a viral and host gene Cell Host Microbe 5 2009 84 94
74. K.A. Woodrow, Y. Cu, C.J. Booth, J.K. Saucier-Sawyer, M.J. Wood, and W.M. Saltzman Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA Nat. Mater. 8 2009 526 533
75. J.M. Steinbach, C.E. Weller, C.J. Booth, and W.M. Saltzman Polymer nanoparticles encapsulating siRNA for treatment of HSV-2 genital infection J. Control. Release 162 2012 102 110
76. A.S. Ham, M.R. Cost, A.B. Sassi, C.S. Dezzutti, and L.C. Rohan Targeted delivery of PSC-RANTES for HIV-1 prevention using biodegradable nanoparticles Pharm. Res. 26 2009 502 511
77. T. Zhang, T.F. Sturgis, and B.B. Youan pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission Eur. J. Pharm. Biopharm. 79 2011 526 536
78. J.W. Yoo, N. Giri, and C.H. Lee pH-sensitive Eudragit nanoparticles for mucosal drug delivery Int. J. Pharm. 403 2011 262 267
79. J. Meng, T.F. Sturgis, and B.B. Youan Engineering tenofovir loaded chitosan nanoparticles to maximize microbicide mucoadhesion Eur. J. Pharm. Sci. 44 2011 57 67
80. D. Belletti, G. Tosi, F. Forni, M.C. Gamberini, C. Baraldi, M.A. Vandelli, and B. Ruozi Chemico-physical investigation of tenofovir loaded polymeric nanoparticles Int. J. Pharm. 436 2012 753 763
81. S.L. Achilles, P.B. Shete, K.J. Whaley, T.R. Moench, and R.A. Cone Microbicide efficacy and toxicity tests in a mouse model for vaginal transmission of Chlamydia trachomatis Sex. Transm. Dis. 29 2002 655 664 (Pubitemid 35266407)
82. T. Chaowanachan, E. Krogstad, C. Ball, and K.A. Woodrow Drug synergy of tenofovir and nanoparticle-based antiretrovirals for HIV prophylaxis PLoS One 8 2013 e61416
83. J. das Neves, J. Michiels, K.K. Arien, G. Vanham, M. Amiji, M.F. Bahia, and B. Sarmento Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine Pharm. Res. 29 2012 1468 1484
84. J. das Neves, M. Amiji, M.F. Bahia, and B. Sarmento Assessing the physical-chemical properties and stability of dapivirine-loaded polymeric nanoparticles Int. J. Pharm. 456 2013 307 314
85. J. das Neves, F. Araujo, F. Andrade, J. Michiels, K.K. Arien, G. Vanham, M. Amiji, M.F. Bahia, and B. Sarmento In vitro and ex vivo evaluation of polymeric nanoparticles for vaginal and rectal delivery of the anti-HIV drug dapivirine Mol. Pharm. 10 2013 2793 2807
86. J. das Neves, F. Araujo, F. Andrade, M. Amiji, M.F. Bahia, and B. Sarmento Biodistribution and pharmacokinetics of dapivirine-loaded nanoparticles after vaginal delivery in mice Pharm. Res. 2014 10.1007/s11095-013-1287-x
87. A.A. Date, A. Shibata, M. Goede, B. Sanford, K. La Bruzzo, M. Belshan, and C.J. Destache Development and evaluation of a thermosensitive vaginal gel containing raltegravir + efavirenz loaded nanoparticles for HIV prophylaxis Antivir. Res. 96 2012 430 436
88. W. Peng, C. Dunton, D. Holtz, M. Parva, K. Stampler, M. Forwood, R. Gogoi, M.J. Lace, D.G. Anderson, and J.A. Sawicki DNA nanotherapy for pre-neoplastic cervical lesions Gynecol. Oncol. 128 2013 101 106
89. J. Blum, C.E. Weller, C.J. Booth, I. Babar, X. Liang, F. Slack, and W.M. Saltzman Prevention of K-Ras- and Pten-mediated intravaginal tumors by treatment with camptothecin-loaded PLGA nanoparticles Drug Deliv. Transl. Res. 1 2011 383 394
90. A.D. Bangham, M.M. Standish, and J.C. Watkins Diffusion of univalent ions across the lamellae of swollen phospholipids J. Mol. Biol. 13 1965 238 252
91. T.M. Allen, and P.R. Cullis Liposomal drug delivery systems: from concept to clinical applications Adv. Drug Deliv. Rev. 65 2013 36 48
92. H.I. Chang, and M.K. Yeh Clinical development of liposome-based drugs: formulation, characterization, and therapeutic efficacy Int. J. Nanomedicine 7 2012 49 60
93. M. Caron, G. Besson, S.L. Etenna, A. Mintsa-Ndong, S. Mourtas, A. Radaelli, G. Morghen Cde, R. Loddo, P. La Colla, S.G. Antimisiaris, and M. Kazanji Protective properties of non-nucleoside reverse transcriptase inhibitor (MC1220) incorporated into liposome against intravaginal challenge of Rhesus macaques with RT-SHIV Virology 405 2010 225 233
94. L. Wang, A.B. Sassi, D. Patton, C. Isaacs, B.J. Moncla, P. Gupta, and L.C. Rohan Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention Drug Dev. Ind. Pharm. 38 2012 995 1007
95. K. Konopka, B.R. Davis, C.E. Larsen, D.R. Alford, R.J. Debs, and N. Duzgunes Liposomes modulate human immunodeficiency virus infectivity J. Gen. Virol. 71 Pt 12 1990 2899 2907
96. N.K. Malavia, D. Zurakowski, A. Schroeder, A.M. Princiotto, A.R. Laury, H.E. Barash, J. Sodroski, R. Langer, N. Madani, and D.S. Kohane Liposomes for HIV prophylaxis Biomaterials 32 2011 8663 8668
97. J.L. Hood, A.P. Jallouk, N. Campbell, L. Ratner, and S.A. Wickline Cytolytic nanoparticles attenuate HIV-1 infectivity Antivir. Ther. 18 2013 95 103
98. M. Wachinger, A. Kleinschmidt, D. Winder, N. von Pechmann, A. Ludvigsen, M. Neumann, R. Holle, B. Salmons, V. Erfle, and R. Brack-Werner Antimicrobial peptides melittin and cecropin inhibit replication of human immunodeficiency virus 1 by suppressing viral gene expression J. Gen. Virol. 79 Pt 4 1998 731 740 (Pubitemid 28161947)
99. S. Maher, and S. McClean Melittin exhibits necrotic cytotoxicity in gastrointestinal cells which is attenuated by cholesterol Biochem. Pharmacol. 75 2008 1104 1114
100. D. Alukda, T. Sturgis, and B.B. Youan Formulation of tenofovir-loaded functionalized solid lipid nanoparticles intended for HIV prevention J. Pharm. Sci. 100 2011 3345 3356
101. S. Yang, Y. Chen, R. Ahmadie, and E.A. Ho Advancements in the field of intravaginal siRNA delivery J. Control. Release 167 2013 29 39
102. L. Zeitlin, K.J. Whaley, T.A. Hegarty, T.R. Moench, and R.A. Cone Tests of vaginal microbicides in the mouse genital herpes model Contraception 56 1997 329 335 (Pubitemid 28022887)
103. Z. Pavelic, N. Skalko-Basnet, and I. Jalsenjak Liposomes containing drugs for treatment of vaginal infections Eur. J. Pharm. Sci. 8 1999 345 351 (Pubitemid 29325027)
104. Z. Pavelic, N. Skalko-Basnet, and R. Schubert Liposomal gels for vaginal drug delivery Int. J. Pharm. 219 2001 139 149 (Pubitemid 32391373)
105. Z. Pavelic, N. Skalko-Basnet, J. Filipovic-Grcic, A. Martinac, and I. Jalsenjak Development and in vitro evaluation of a liposomal vaginal delivery system for acyclovir J. Control. Release 106 2005 34 43 (Pubitemid 41140079)
106. S. Karimunnisa, and P. Atmaram Mucoadhesive nanoliposomal formulation for vaginal delivery of an antifungal Drug Dev. Ind. Pharm. 39 2013 1328 1337
107. D.B. Patel, and J.K. Patel Liposomal drug delivery of metronidazole for the local treatment of vaginitis Int. J. Pharm. Sci. Nanotechnol. 2 2009 421 427
108. Z. Vanic, J. Hurler, K. Ferderber, P. Golja Gasparovic, N. Skalko-Basnet, and J. Filipovic-Grcic Novel vaginal drug delivery system: deformable propylene glycol liposomes-in-hydrogel J. Liposome Res. 24 2014 27 36
109. Z. Vanic, A. Hafner, M. Bego, and N. Skalko-Basnet Characterization of various deformable liposomes with metronidazole Drug Dev. Ind. Pharm. 39 2013 481 488
110. P. Basnet, H. Hussain, I. Tho, and N. Skalko-Basnet Liposomal delivery system enhances anti-inflammatory properties of curcumin J. Pharm. Sci. 101 2012 598 609
111. J.W. Kang, E. Davaa, Y.T. Kim, and J.S. Park A new vaginal delivery system of amphotericin B: a dispersion of cationic liposomes in a thermosensitive gel J. Drug Target. 18 2010 637 644
112. A.R. Menjoge, R.M. Kannan, and D.A. Tomalia Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications Drug Discov. Today 15 2010 171 185
113. L.C. du Toit, V. Pillay, and Y.E. Choonara Nano-microbicides: challenges in drug delivery, patient ethics and intellectual property in the war against HIV/AIDS Adv. Drug Deliv. Rev. 62 2010 532 546
114. R. Rupp, S.L. Rosenthal, and L.R. Stanberry VivaGel (SPL7013 Gel): a candidate dendrimer - microbicide for the prevention of HIV and HSV infection Int. J. Nanomedicine 2 2007 561 566
115. D. Tyssen, S.A. Henderson, A. Johnson, J. Sterjovski, K. Moore, J. La, M. Zanin, S. Sonza, P. Karellas, M.P. Giannis, G. Krippner, S. Wesselingh, T. McCarthy, P.R. Gorry, P.A. Ramsland, R. Cone, J.R. Paull, G.R. Lewis, and G. Tachedjian Structure activity relationship of dendrimer microbicides with dual action antiviral activity PLoS One 5 2010 e12309
116. J. O'Loughlin, I.Y. Millwood, H.M. McDonald, C.F. Price, J.M. Kaldor, and J.R. Paull Safety, tolerability, and pharmacokinetics of SPL7013 gel (VivaGel): a dose ranging, phase I study Sex. Transm. Dis. 37 2010 100 104
117. A.B. Moscicki, R. Kaul, Y. Ma, M.E. Scott, I.I. Daud, E.A. Bukusi, S. Shiboski, A. Rebbapragada, S. Huibner, and C.R. Cohen Measurement of mucosal biomarkers in a phase 1 trial of intravaginal 3% StarPharma LTD 7013 gel (VivaGel) to assess expanded safety J. Acquir. Immune Defic. Syndr. 59 2012 134 140
118. G. Ramjee, A. Kamali, and S. McCormack The last decade of microbicide clinical trials in Africa: from hypothesis to facts AIDS 24 Suppl. 4 2010 S40 S49
119. T.D. McCarthy, P. Karellas, S.A. Henderson, M. Giannis, D.F. O'Keefe, G. Heery, J.R. Paull, B.R. Matthews, and G. Holan Dendrimers as drugs: discovery and preclinical and clinical development of dendrimer-based microbicides for HIV and STI prevention Mol. Pharm. 2 2005 312 318 (Pubitemid 41186407)
120. J. Peng, Z. Wu, X. Qi, Y. Chen, and X. Li Dendrimers as potential therapeutic tools in HIV inhibition Molecules 18 2013 7912 7929
121. J.M. Harouse, R.G. Collman, and F. Gonzalez-Scarano Human immunodeficiency virus type 1 infection of SK-N-MC cells: domains of gp120 involved in entry into a CD4-negative, galactosyl ceramide/3′ sulfo-galactosyl ceramide-positive cell line J. Virol. 69 1995 7383 7390
122. N. Yahi, S. Baghdiguian, H. Moreau, and J. Fantini Galactosyl ceramide (or a closely related molecule) is the receptor for human immunodeficiency virus type 1 on human colon epithelial HT29 cells J. Virol. 66 1992 4848 4854
123. S. Han, T. Kanamoto, H. Nakashima, and T. Yoshida Synthesis of a new amphiphilic glycodendrimer with antiviral functionality Carbohydr. Polym. 90 2012 1061 1068
124. R.D. Kensinger, B.C. Yowler, A.J. Benesi, and C.L. Schengrund Synthesis of novel, multivalent glycodendrimers as ligands for HIV-1 gp120 Bioconjug. Chem. 15 2004 349 358 (Pubitemid 38365195)
125. A. Rosa Borges, L. Wieczorek, B. Johnson, A.J. Benesi, B.K. Brown, R.D. Kensinger, F.C. Krebs, B. Wigdahl, R. Blumenthal, A. Puri, F.E. McCutchan, D.L. Birx, V.R. Polonis, and C.L. Schengrund Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1 Virology 408 2010 80 88
126. J. Rojo, and R. Delgado Glycodendritic structures: promising new antiviral drugs J. Antimicrob. Chemother. 54 2004 579 581 (Pubitemid 39263896)
127. G. Tabarani, J.J. Reina, C. Ebel, C. Vives, H. Lortat-Jacob, J. Rojo, and F. Fieschi Mannose hyperbranched dendritic polymers interact with clustered organization of DC-SIGN and inhibit gp120 binding FEBS Lett. 580 2006 2402 2408 (Pubitemid 44389366)
128. M. Ciobanu, K.T. Huang, J.P. Daguer, S. Barluenga, O. Chaloin, E. Schaeffer, C.G. Mueller, D.A. Mitchell, and N. Winssinger Selection of a synthetic glycan oligomer from a library of DNA-templated fragments against DC-SIGN and inhibition of HIV gp120 binding to dendritic cells Chem. Commun. 47 2011 9321 9323
129. L. Chonco, M. Pion, E. Vacas, B. Rasines, M. Maly, M.J. Serramia, L. Lopez-Fernandez, J. De la Mata, S. Alvarez, R. Gomez, and M.A. Munoz-Fernandez Carbosilane dendrimer nanotechnology outlines of the broad HIV blocker profile J. Control. Release 161 2012 949 958
130. M. Ionov, K. Ciepluch, B. Klajnert, S. Glinska, R. Gomez-Ramirez, F.J. de la Mata, M.A. Munoz-Fernandez, and M. Bryszewska Complexation of HIV derived peptides with carbosilane dendrimers Colloids Surf. B: Biointerfaces 101 2013 236 242
131. T. Dutta, M. Garg, and N.K. Jain Targeting of efavirenz loaded tuftsin conjugated poly(propyleneimine) dendrimers to HIV infected macrophages in vitro Eur. J. Pharm. Sci. 34 2008 181 189
132. T. Dutta, and N.K. Jain Targeting potential and anti-HIV activity of lamivudine loaded mannosylated poly(propyleneimine) dendrimer Biochim. Biophys. Acta 1770 2007 681 686 (Pubitemid 46281473)
133. N. Weber, P. Ortega, M.I. Clemente, D. Shcharbin, M. Bryszewska, F.J. de la Mata, R. Gomez, and M.A. Munoz-Fernandez Characterization of carbosilane dendrimers as effective carriers of siRNA to HIV-infected lymphocytes J. Control. Release 132 2008 55 64
134. V. Dzmitruk, D. Shcharbin, E. Pedziwiatr-Werbicka, and M. Bryszewska Dendrimers in Anti-HIV Therapy 2011
135. A.R. Menjoge, R.S. Navath, A. Asad, S. Kannan, C.J. Kim, R. Romero, and R.M. Kannan Transport and biodistribution of dendrimers across human fetal membranes: implications for intravaginal administration of dendrimer-drug conjugates Biomaterials 31 2010 5007 5021
136. B. Wang, R.S. Navath, A.R. Menjoge, B. Balakrishnan, R. Bellair, H. Dai, R. Romero, S. Kannan, and R.M. Kannan Inhibition of bacterial growth and intramniotic infection in a guinea pig model of chorioamnionitis using PAMAM dendrimers Int. J. Pharm. 395 2010 298 308
137. R.S. Navath, A.R. Menjoge, H. Dai, R. Romero, S. Kannan, and R.M. Kannan Injectable PAMAM dendrimer-PEG hydrogels for the treatment of genital infections: formulation and in vitro and in vivo evaluation Mol. Pharm. 8 2011 1209 1223
138. J.A. Lemire, J.J. Harrison, and R.J. Turner Antimicrobial activity of metals: mechanisms, molecular targets and applications Nat. Rev. Microbiol. 11 2013 371 384
139. J.L. Elechiguerra, J.L. Burt, J.R. Morones, A. Camacho-Bragado, X. Gao, H.H. Lara, and M.J. Yacaman Interaction of silver nanoparticles with HIV-1 J. Nanobiotechnol. 3 2005 6
140. H.H. Lara, N.V. Ayala-Nunez, L. Ixtepan-Turrent, and C. Rodriguez-Padilla Mode of antiviral action of silver nanoparticles against HIV-1 J. Nanobiotechnol. 8 2010 1
141. H.H. Lara, L. Ixtepan-Turrent, E.N. Garza-Trevino, and C. Rodriguez-Padilla PVP-coated silver nanoparticles block the transmission of cell-free and cell-associated HIV-1 in human cervical culture J. Nanobiotechnol. 8 2010 15
142. A. Mohammed Fayaz, Z. Ao, M. Girilal, L. Chen, X. Xiao, P. Kalaichelvan, and X. Yao Inactivation of microbial infectiousness by silver nanoparticles-coated condom: a new approach to inhibit HIV- and HSV-transmitted infection Int. J. Nanomedicine 7 2012 5007 5018
143. O. Martinez-Avila, L.M. Bedoya, M. Marradi, C. Clavel, J. Alcami, and S. Penades Multivalent manno-glyconanoparticles inhibit DC-SIGN-mediated HIV-1 trans-infection of human T cells Chembiochem 10 2009 1806 1809
144. O. Martinez-Avila, K. Hijazi, M. Marradi, C. Clavel, C. Campion, C. Kelly, and S. Penades Gold manno-glyconanoparticles: multivalent systems to block HIV-1 gp120 binding to the lectin DC-SIGN Chemistry 15 2009 9874 9888
145. M.C. Bowman, T.E. Ballard, C.J. Ackerson, D.L. Feldheim, D.M. Margolis, and C. Melander Inhibition of HIV fusion with multivalent gold nanoparticles J. Am. Chem. Soc. 130 2008 6896 6897 (Pubitemid 351770109)
146. P. Di Gianvincenzo, M. Marradi, O.M. Martinez-Avila, L.M. Bedoya, J. Alcami, and S. Penades Gold nanoparticles capped with sulfate-ended ligands as anti-HIV agents Bioorg. Med. Chem. Lett. 20 2010 2718 2721
147. X. Ma, Y. Wu, S. Jin, Y. Tian, X. Zhang, Y. Zhao, L. Yu, and X.J. Liang Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment ACS Nano 5 2011 8629 8639
148. D.J. Irvine, M.A. Swartz, and G.L. Szeto Engineering synthetic vaccines using cues from natural immunity Nat. Mater. 12 2013 978 990
149. Q. He, A.R. Mitchell, S.L. Johnson, C. Wagner-Bartak, T. Morcol, and S.J. Bell Calcium phosphate nanoparticle adjuvant Clin. Diagn. Lab. Immunol. 7 2000 899 903 (Pubitemid 32244486)
150. Q. He, A. Mitchell, T. Morcol, and S.J. Bell Calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type 2 Clin. Diagn. Lab. Immunol. 9 2002 1021 1024 (Pubitemid 34988469)
151. B. Ballou, S.K. Andreko, E. Osuna-Highley, M. McRaven, T. Catalone, M.P. Bruchez, T.J. Hope, and M.E. Labib Nanoparticle transport from mouse vagina to adjacent lymph nodes PLoS One 7 2012 e51995
152. B. Jeong, S.W. Kim, and Y.H. Bae Thermosensitive sol-gel reversible hydrogels Advanced drug delivery reviews 54 2012 37 51