Vaginal Drug Delivery

  • Emily A. Krogstad
  • Michael J. Rathbone
  • Kim A. Woodrow
Part of the Advances in Delivery Science and Technology book series (ADST)


While the human vagina has great potential as an administration route for drug delivery, several challenges remain due to its variable nature and innate barriers. In this chapter, the distinctive barriers resulting from the anatomy and physiology of the vagina are presented. We then discuss strategies to rationally design vaginal drug delivery systems to maximize the efficacy and control the kinetics of drug delivery across the vaginal mucosa. The physical, rheological, and retentive properties of current vaginal dosage forms are compared as well as pharmacological considerations for vaginal delivery. Emerging nanomaterial strategies for vaginal drug delivery including nanoparticles and electrospun fibers are reviewed in depth, with a specific focus on HIV microbicide applications. The underlying principles for designing vaginal drug delivery systems that are discussed here have relevance for many reproductive health and mucosal delivery applications.


Human Immunodeficiency Virus Vaginal Delivery Electrospun Fiber Human Immunodeficiency Virus Prevention PLGA Nanoparticles 
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.





Cellulose acetate phthalate


Cetyltrimethylammonium bromide


Cervicovaginal fluid






Highly active antiretroviral therapy


Human immunodeficiency virus


Herpes simplex virus 2


Intravaginal ring


Nano-antiretroviral therapy


Nucleotide reverse transcriptase inhibitor


Peripheral blood mononuclear cell




Poly(d,l)-lactic acid


Poly(ethylene glycol)


Poly(ethylene oxide)


Poly(lactic acid)


Poly(lactic-co-glycolic acid)


Poly(l-lactic acid)




Poly(vinyl alcohol)


Simian-human immunodeficiency virus


Simian immunodeficiency virus


Sodium lauryl sulfate




Sexually transmitted infection


Tenofovir disoproxil fumarate




Vaginal fluid simulant


Vitamin E/5 kDa PEG


  1. 1.
    Brannon-Peppas L (1993) Novel vaginal drug release applications. Adv Drug Deliv Rev 11:169–177Google Scholar
  2. 2.
    Benziger DP, Edelson J (1983) Absorption from the vagina. Drug Metab Rev 14:137–168PubMedGoogle Scholar
  3. 3.
    Platzner W, Poisel S (1978) Functional anatomy of the human vagina. In: Hafez ES, Evans TN (eds) Human reproductive medicine: the human vagina. North Holland, New York, NY, pp 39–54Google Scholar
  4. 4.
    Richardson JL, Illum L (1992) (D) Routes of delivery: case studies: (8) the vaginal route of peptide and protein drug delivery. Adv Drug Deliv Rev 8:341–366Google Scholar
  5. 5.
    Hafez ESE, Evans TN (1978) Human reproductive medicine: the human vagina. Elsevier North-Holland, New York, NY. ISBN 072040648XGoogle Scholar
  6. 6.
    Knuth K, Amiji M, Robinson JR (1993) Hydrogel delivery systems for vaginal and oral applications: formulation and biological considerations. Adv Drug Deliv Rev 11:137–167Google Scholar
  7. 7.
    Burgos MH, Roig de Vargas-Linaires CE (1978) Ultrastructure of the vaginal mucosa. In: Hafez ES, Evans TN (eds) Human reproductive medicine: the human vagina. North Holland, New York, NY, pp 63–93Google Scholar
  8. 8.
    Paavonen J (1982) Physiology and ecology of the vagina. Scand J Infect Dis Suppl 40:31–35Google Scholar
  9. 9.
    Wagner G, Levin RJ (1978) Vaginal fluid. In: Hafez ES, Evans TN (eds) Human reproductive medicine: the human vagina. North Holland, New York, NY, pp 121–137Google Scholar
  10. 10.
    Katz DF, Dunmire EN (1993) Cervical mucus: problems and opportunities for drug delivery via the vagina and cervix. Adv Drug Deliv Rev 11:385–401Google Scholar
  11. 11.
    Kistner RW (1978) Physiology of the vagina. In: Hafez ES, Evans TN (eds) Human reproductive medicine: the human vagina. North Holland, New York, NY, pp 109–120Google Scholar
  12. 12.
    Lee VHL, Yamamoto A (1989) Penetration and enzymatic barriers to peptide and protein absorption. Adv Drug Deliv Rev 4:171–207Google Scholar
  13. 13.
    Chien YW (1982) Controlled administration of estrus-synchronizing agents in livestock. In: Chien YW (ed) Novel drug delivery systems. Marcel Dekker, New York, NY, pp 51–95Google Scholar
  14. 14.
    Woolfson D, Malcolm K (2008) Intravaginal drug delivery technologies. In: Modified-release drug delivery technology, 2nd edition. Rathbone MJ, Roberts K, Lane ME, Hadgraft J (Eds.). Informa, New York, NY, pp 481–498Google Scholar
  15. 15.
    Haase AT (2010) Targeting early infection to prevent HIV-1 mucosal transmission. Nature 464:217–223PubMedGoogle Scholar
  16. 16.
    Ma Z, Lü FX, Torten M, Miller CJ (2001) The number and distribution of immune cells in the cervicovaginal mucosa remain constant throughout the menstrual cycle of rhesus macaques. Clin Immunol 100:240–249PubMedGoogle Scholar
  17. 17.
    Zhang Z-Q, Wietgrefe SW, Li Q, Shore MD, Duan L, Reilly C, Lifson JD, Haase AT (2004) Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection. Proc Natl Acad Sci U S A 101:5640–5645PubMedCentralPubMedGoogle Scholar
  18. 18.
    Pudney J, Quayle AJ, Anderson DJ (2005) Immunological microenvironments in the human vagina and cervix: mediators of cellular immunity are concentrated in the cervical transformation zone1. Biol Reprod 73:1253–1263PubMedGoogle Scholar
  19. 19.
    Saltzman WM (2001) Drug delivery: engineering principles for drug therapy: engineering principles for drug therapy. Oxford University Press, New York, NYGoogle Scholar
  20. 20.
    Schwartz JL, Rountree W, Kashuba ADM, Brache V, Creinin MD, Poindexter A, Kearney BP (2011) A multi-compartment, single and multiple dose pharmacokinetic study of the vaginal candidate microbicide 1 % tenofovir gel. PLoS One 6:e25974PubMedCentralPubMedGoogle Scholar
  21. 21.
    Patterson KB, Prince HA, Kraft E, Jenkins AJ, Shaheen NJ, Rooney JF, Cohen MS, Kashuba ADM (2011) Penetration of Tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med 3:112re4PubMedCentralPubMedGoogle Scholar
  22. 22.
    Durand-Gasselin L, Van Rompay KKA, Vela JE, Henne IN, Lee WA, Rhodes GR, Ray AS (2009) Nucleotide analogue prodrug tenofovir disoproxil enhances lymphoid cell loading following oral administration in monkeys. Mol Pharm 6:1145–1151PubMedCentralPubMedGoogle Scholar
  23. 23.
    Karim SSA, Kashuba AD, Werner L, Karim QA (2011) Drug concentrations after topical and oral antiretroviral pre-exposure prophylaxis: implications for HIV prevention in women. Lancet 378:279–281PubMedCentralPubMedGoogle Scholar
  24. 24.
    Karim Q, Karim SSA, Frohlich JA, Grobler AC, Baxter C, Mansoor LE (2010) Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329:1168Google Scholar
  25. 25.
    Achilles SL, Shete PB, Whaley KJ, Moench TR, Cone RA (2002) Microbicide efficacy and toxicity tests in a mouse model for vaginal transmission of Chlamydia trachomatis. Sex Transm Dis 29:655–664PubMedGoogle Scholar
  26. 26.
    Zhang Z-Q, Schuler T, Zupancic M et al (1999) Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 286:1353–1357PubMedGoogle Scholar
  27. 27.
    Geonnotti AR, Peters JJ, Katz DF (2005) Erosion of microbicide formulation coating layers: effects of contact and shearing with vaginal fluid or semen. J Pharm Sci 94:1705–1712PubMedGoogle Scholar
  28. 28.
    Doncel GF (2006) Exploiting common targets in human fertilization and HIV infection: development of novel contraceptive microbicides. Hum Reprod Update 12:103–117PubMedGoogle Scholar
  29. 29.
    Klasse PJ, Shattock R, Moore JP (2008) Antiretroviral drug-based microbicides to prevent HIV-1 sexual transmission. Annu Rev Med 59:455–471PubMedGoogle Scholar
  30. 30.
    Friend DR, Doncel GF (2010) Combining prevention of HIV-1, other sexually transmitted infections and unintended pregnancies: development of dual-protection technologies. Antiviral Res 88(Suppl 1):S47–S54PubMedGoogle Scholar
  31. 31.
    Pope M, Haase AT (2003) Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nat Med 9:847–852PubMedGoogle Scholar
  32. 32.
    Ndesendo V, Pillay V, Choonara Y, Buchmann E, Bayever D, Meyer L (2008) A review of current intravaginal drug delivery approaches employed for the prophylaxis of HIV/AIDS and prevention of sexually transmitted infections. AAPS PharmSciTech 9:505–520PubMedCentralPubMedGoogle Scholar
  33. 33.
    Andrews GP, Donnelly L, Jones DS, Curran RM, Morrow RJ, Woolfson AD, Malcolm RK (2009) Characterization of the rheological, mucoadhesive, and drug release properties of highly structured Gel platforms for intravaginal drug delivery. Biomacromolecules 10:2427–2435PubMedCentralPubMedGoogle Scholar
  34. 34.
    Dyer JR, Kazembe P, Vernazza PL et al (1998) High levels of human immunodeficiency virus type 1 in blood and semen of seropositive men in sub-Saharan Africa. J Infect Dis 177:1742–1746PubMedGoogle Scholar
  35. 35.
    Tsai C-C, Emau P, Jiang Y, Tian B, Morton WR, Gustafson KR, Boyd MR (2003) Cyanovirin-N gel as a topical microbicide prevents rectal transmission of SHIV89.6P in macaques. AIDS Res Hum Retroviruses 19:535–541PubMedGoogle Scholar
  36. 36.
    Lederman MM, Veazey RS, Offord R et al (2004) Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science 306:485–487PubMedGoogle Scholar
  37. 37.
    Tsai C-C, Emau P, Jiang Y, Agy MB, Shattock RJ, Schmidt A, Morton WR, Gustafson KR, Boyd MR (2004) Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models. AIDS Res Hum Retroviruses 20:11–18PubMedGoogle Scholar
  38. 38.
    Boadi T, Schneider E, Chung S, Tsai L, Gettie A, Ratterree M, Blanchard J, Neurath AR, Cheng-Mayer C (2005) Cellulose acetate 1,2-benzenedicarboxylate protects against challenge with pathogenic X4 and R5 simian/human immunodeficiency virus. AIDS 19:1587–1594PubMedGoogle Scholar
  39. 39.
    Wang Y, Abel K, Lantz K, Krieg AM, McChesney MB, Miller CJ (2005) The Toll-like receptor 7 (TLR7) agonist, imiquimod, and the TLR9 agonist, CpG ODN, induce antiviral cytokines and chemokines but do not prevent vaginal transmission of simian immunodeficiency virus when applied intravaginally to rhesus macaques. J Virol 79:14355–14370PubMedCentralPubMedGoogle Scholar
  40. 40.
    Klasse PJ, Shattock RJ, Moore JP (2006) Which topical microbicides for blocking HIV-1 transmission will work in the real world? PLoS Med 3:e351PubMedCentralPubMedGoogle Scholar
  41. 41.
    Herrera C, Cranage M, McGowan I, Anton P, Shattock RJ (2009) Reverse transcriptase inhibitors as potential colorectal microbicides. Antimicrob Agents Chemother 53:1797–1807PubMedCentralPubMedGoogle Scholar
  42. 42.
    Garg S, Tambwekar KR, Vermani K, Kandarapu R, Garg A, Waller DP, Zaneveld LJD (2003) Development pharmaceutics of microbicide formulations. Part II: formulation, evaluation, and challenges. AIDS Patient Care STDS 17:377–399PubMedGoogle Scholar
  43. 43.
    Malcolm RK, Edwards K-L, Kiser P, Romano J, Smith TJ (2010) Advances in microbicide vaginal rings. Antiviral Res 88(Suppl 1):S30–S39PubMedGoogle Scholar
  44. 44.
    Rohan LC, Sassi AB (2009) Vaginal drug delivery systems for HIV prevention. AAPS J 11:78–87PubMedGoogle Scholar
  45. 45.
    Dobaria N, Badhan A, Mashru R (2009) A novel itraconazole bioadhesive film for vaginal delivery: design, optimization, and physicodynamic characterization. AAPS PharmSciTech 10:951–959PubMedCentralPubMedGoogle Scholar
  46. 46.
    Asane GS, Nirmal SA, Rasal KB, Naik AA, Mahadik MS, Rao YM (2008) Polymers for mucoadhesive drug delivery system: a current status. Drug Dev Ind Pharm 34:1246–1266PubMedGoogle Scholar
  47. 47.
    Ham A, Cost M, Sassi A, Dezzutti C, Rohan L (2009) Targeted delivery of PSC-RANTES for HIV-1 prevention using biodegradable nanoparticles. Pharm Res 26:502–511PubMedGoogle Scholar
  48. 48.
    Akil A, Parniak M, Dezzutti C, Moncla B, Cost M, Li M, Rohan L (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 1:209–222PubMedCentralPubMedGoogle Scholar
  49. 49.
    Zhang L, Gu F, Chan J, Wang A, Langer R, Farokhzad O (2007) Nanoparticles in medicine: therapeutic applications and developments. Clin Pharmacol Ther 83:761–769PubMedGoogle Scholar
  50. 50.
    Rawat M, Singh D, Saraf S, Saraf S (2006) Nanocarriers: promising vehicle for bioactive drugs. Biol Pharm Bull 29:1790–1798PubMedGoogle Scholar
  51. 51.
    Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55:329–347PubMedGoogle Scholar
  52. 52.
    Ganta S, Devalapally H, Shahiwala A, Amiji M (2008) A review of stimuli-responsive nanocarriers for drug and gene delivery. J Control Release 126:187–204PubMedGoogle Scholar
  53. 53.
    Mallipeddi R, Rohan LC (2010) Nanoparticle-based vaginal drug delivery systems for HIV prevention. Expert Opin Drug Deliv 7:37–48PubMedGoogle Scholar
  54. 54.
    Panyam J, Zhou W-Z, Prabha S, Sahoo SK, Labhasetwar V (2002) Rapid endo-lysosomal escape of poly(dl-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery. FASEB J 16:1217–1226PubMedGoogle Scholar
  55. 55.
    Cohen H, Levy RJ, Gao J, Fishbein I, Kousaev V, Sosnowski S, Slomkowski S, Golomb G (2000) Sustained delivery and expression of DNA encapsulated in polymeric nanoparticles. Gene Ther 7:1896–1905PubMedGoogle Scholar
  56. 56.
    Destache CJ, Belgum T, Christensen K, Shibata A, Sharma A, Dash A (2009) Combination antiretroviral drugs in PLGA nanoparticle for HIV-1. BMC Infect Dis 9:198PubMedCentralPubMedGoogle Scholar
  57. 57.
    Alukda D, Sturgis T, Youan B-BC (2011) Formulation of tenofovir-loaded functionalized solid lipid nanoparticles intended for HIV prevention. J Pharm Sci 100:3345–3356PubMedCentralPubMedGoogle Scholar
  58. 58.
    Liu X, Howard KA, Dong M, Andersen M, Rahbek UL, Johnsen MG, Hansen OC, Besenbacher F, Kjems J (2007) The influence of polymeric properties on chitosan/siRNA nanoparticle formulation and gene silencing. Biomaterials 28:1280–1288PubMedGoogle Scholar
  59. 59.
    Woodrow KA, Cu Y, Booth CJ, Saucier-Sawyer JK, Wood MJ, Saltzman WM (2009) Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA. Nat Mater 8:526–533PubMedCentralPubMedGoogle Scholar
  60. 60.
    Perera G, Greindl M, Palmberger TF, Bernkop-Schnürch A (2009) Insulin-loaded poly(acrylic acid)-cysteine nanoparticles: stability studies towards digestive enzymes of the intestine. Drug Deliv 16:254–260PubMedGoogle Scholar
  61. 61.
    Chakravarthi S, Robinson D, De S (2007) Nanoparticles prepared using natural and synthetic polymers. In: Thassu D (ed) Nanoparticulate drug delivery systems. Informa Healthcare, New York, NY, pp 51–60Google Scholar
  62. 62.
    Xiong XY, Tam KC, Gan LH (2005) Release kinetics of hydrophobic and hydrophilic model drugs from pluronic F127/poly(lactic acid) nanoparticles. J Control Release 103:73–82PubMedGoogle Scholar
  63. 63.
    Das Neves J, Michiels J, Ariën K, Vanham G, Amiji M, Bahia M, Sarmento B (2012) Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine. Pharm Res 29:1468–1484PubMedGoogle Scholar
  64. 64.
    Turos E, Reddy GSK, Greenhalgh K, Ramaraju P, Abeylath SC, Jang S, Dickey S, Lim DV (2007) Penicillin-bound polyacrylate nanoparticles: restoring the activity of β-lactam antibiotics against MRSA. Bioorg Med Chem Lett 17:3468–3472PubMedCentralPubMedGoogle Scholar
  65. 65.
    Dang JM, Leong KW (2006) Natural polymers for gene delivery and tissue engineering. Adv Drug Deliv Rev 58:487–499PubMedGoogle Scholar
  66. 66.
    Jain RA (2000) The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21:2475–2490PubMedGoogle Scholar
  67. 67.
    Bilati U, Allémann E, Doelker E (2005) Development of a nanoprecipitation method intended for the entrapment of hydrophilic drugs into nanoparticles. Eur J Pharm Sci 24:67–75PubMedGoogle Scholar
  68. 68.
    Bock N, Dargaville TR, Woodruff MA (2012) Electrospraying of polymers with therapeutic molecules: state of the art. Prog Polym Sci 37:1510–1551Google Scholar
  69. 69.
    Avgoustakis K, Beletsi A, Panagi Z, Klepetsanis P, Livaniou E, Evangelatos G, Ithakissios DS (2003) Effect of copolymer composition on the physicochemical characteristics, in vitro stability, and biodistribution of PLGA–mPEG nanoparticles. Int J Pharm 259:115–127PubMedGoogle Scholar
  70. 70.
    Santander-Ortega MJ, Csaba N, Alonso MJ, Ortega-Vinuesa JL, Bastos-González D (2007) Stability and physicochemical characteristics of PLGA, PLGA:poloxamer and PLGA:poloxamine blend nanoparticles: a comparative study. Colloids Surf A Physicochem Eng Asp 296:132–140Google Scholar
  71. 71.
    Meng J, Sturgis TF, Youan B-BC (2011) Engineering tenofovir loaded chitosan nanoparticles to maximize microbicide mucoadhesion. Eur J Pharm Sci 44:57–67PubMedCentralPubMedGoogle Scholar
  72. 72.
    Dobrovolskaia MA, McNeil SE (2007) Immunological properties of engineered nanomaterials. Nat Nanotechnol 2:469–478PubMedGoogle Scholar
  73. 73.
    Owens DE III, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102PubMedGoogle Scholar
  74. 74.
    Ensign LM, Tang BC, Wang Y-Y, Tse TA, Hoen T, Cone R, Hanes J (2012) Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci Transl Med 4:138ra79PubMedGoogle Scholar
  75. 75.
    Yu T, Wang Y-Y, Yang M et al (2012) Biodegradable mucus-penetrating nanoparticles composed of diblock copolymers of polyethylene glycol and poly(lactic-co-glycolic acid). Drug Deliv Transl Res 2:124–128Google Scholar
  76. 76.
    Zhang T, Sturgis TF, Youan B-BC (2011) pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission. Eur J Pharm Biopharm 79:526–536PubMedCentralPubMedGoogle Scholar
  77. 77.
    Yoo J-W, Giri N, Lee CH (2011) pH-sensitive eudragit nanoparticles for mucosal drug delivery. Int J Pharm 403:262–267PubMedGoogle Scholar
  78. 78.
    Takeuchi H, Yamamoto H, Kawashima Y (2001) Mucoadhesive nanoparticulate systems for peptide drug delivery. Adv Drug Deliv Rev 47:39–54PubMedGoogle Scholar
  79. 79.
    Lai SK, Wang Y-Y, Hanes J (2009) Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 61:158–171PubMedCentralPubMedGoogle Scholar
  80. 80.
    Das Neves J, Amiji M, Sarmento B (2011) Mucoadhesive nanosystems for vaginal microbicide development: friend or foe? Wiley Interdiscip Rev Nanomed Nanobiotechnol 3:389–399PubMedGoogle Scholar
  81. 81.
    Lai SK, Wang Y-Y, Hida K, Cone R, Hanes J (2009) Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proc Natl Acad Sci 107:598–603PubMedGoogle Scholar
  82. 82.
    Das Neves J, Rocha CMR, Gonçalves MP, Carrier RL, Amiji M, Bahia MF, Sarmento B (2012) Interactions of microbicide nanoparticles with a simulated vaginal fluid. Mol Pharm 9:3347–3356PubMedGoogle Scholar
  83. 83.
    Cone RA (2009) Barrier properties of mucus. Adv Drug Deliv Rev 61:75–85PubMedGoogle Scholar
  84. 84.
    Cu Y, Booth CJ, Saltzman WM (2011) In vivo distribution of surface-modified PLGA nanoparticles following intravaginal delivery. J Control Release 156:258–264PubMedCentralPubMedGoogle Scholar
  85. 85.
    Mert O, Lai SK, Ensign L, Yang M, Wang Y-Y, Wood J, Hanes J (2012) A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles. J Control Release 157:455–460PubMedCentralPubMedGoogle Scholar
  86. 86.
    Wang Y-Y, Lai SK, Suk JS, Pace A, Cone R, Hanes J (2008) Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that “slip” through the human mucus barrier. Angew Chem Int Ed 47:9726–9729Google Scholar
  87. 87.
    Lai SK, Hida K, Shukair S, Wang Y-Y, Figueiredo A, Cone R, Hope TJ, Hanes J (2009) Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J Virol 83:11196–11200PubMedCentralPubMedGoogle Scholar
  88. 88.
    Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515PubMedCentralPubMedGoogle Scholar
  89. 89.
    Zahr AS, Davis CA, Pishko MV (2006) Macrophage uptake of core−shell nanoparticles surface modified with poly(ethylene glycol). Langmuir 22:8178–8185PubMedGoogle Scholar
  90. 90.
    Schäfer V, von Briesen H, Andreesen R, Steffan A-M, Royer C, Tröster S, Kreuter J, Rübsamen-Waigmann H (1992) Phagocytosis of nanoparticles by human immunodeficiency virus (HlV)-infected macrophages: a possibility for antiviral drug targeting. Pharm Res 9:541–546PubMedGoogle Scholar
  91. 91.
    Mainardes RM, Gremião MPD, Brunetti IL, Da Fonseca LM, Khalil NM (2009) Zidovudine-loaded PLA and PLA–PEG blend nanoparticles: influence of polymer type on phagocytic uptake by polymorphonuclear cells. J Pharm Sci 98:257–267PubMedGoogle Scholar
  92. 92.
    Ravel J, Gajer P, Abdo Z et al (2010) Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci 108:4680–4687PubMedGoogle Scholar
  93. 93.
    Owen DH, Katz DF (2005) A review of the physical and chemical properties of human semen and the formulation of a semen simulant. J Androl 26:459–469PubMedGoogle Scholar
  94. 94.
    Nuttall J (2010) Microbicides in the prevention of HIV infection: current status and future directions. Drugs 70:1231–1243PubMedGoogle Scholar
  95. 95.
    Whaley KJ, Hanes J, Shattock R, Cone RA, Friend DR (2010) Novel approaches to vaginal delivery and safety of microbicides: biopharmaceuticals, nanoparticles, and vaccines. Antiviral Res 88(Suppl 1):S55–S66PubMedGoogle Scholar
  96. 96.
    Lembo D, Cavalli R (2010) Nanoparticulate delivery systems for antiviral drugs. Antivir Chem Chemother 21:53–70PubMedGoogle Scholar
  97. 97.
    Bender A, Schäfer V, Steffan AM, Royer C, Kreuter J, Rübsamen-Waigmann H, Von Briesen H (1994) Inhibition of HIV in vitro by antiviral drug-targeting using nanoparticles. Res Virol 145:215–220PubMedGoogle Scholar
  98. 98.
    Shah LK, Amiji MM (2006) Intracellular delivery of saquinavir in biodegradable polymeric nanoparticles for HIV/AIDS. Pharm Res 23:2638–2645PubMedGoogle Scholar
  99. 99.
    Dou H, Morehead J, Destache CJ et al (2007) Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human monocyte-derived macrophages. Virology 358:148–158PubMedGoogle Scholar
  100. 100.
    Hillaireau H, Le Doan T, Couvreur P (2006) Polymer-based nanoparticles for the delivery of nucleoside analogues. J Nanosci Nanotechnol 6:2608–2617PubMedGoogle Scholar
  101. 101.
    Sharma P, Garg S (2010) Pure drug and polymer based nanotechnologies for the improved solubility, stability, bioavailability and targeting of anti-HIV drugs. Adv Drug Deliv Rev 62:491–502PubMedGoogle Scholar
  102. 102.
    Chaowanachan T, Krogstad E, Ball C, Woodrow KA (2013) Drug synergy of tenofovir and nanoparticle-based antiretrovirals for HIV prophylaxis. PLoS One 8(4):e61416PubMedCentralPubMedGoogle Scholar
  103. 103.
    Eszterhas SK, Ilonzo NO, Crozier JE, Celaj S, Howell AL (2011) Nanoparticles containing siRNA to silence CD4 and CCR5 reduce expression of these receptors and inhibit HIV-1 infection in human female reproductive tract tissue explants. Infect Dis Rep. doi: 10.4081/idr.2011.e11 PubMedCentralPubMedGoogle Scholar
  104. 104.
    Van Damme L, Corneli A, Ahmed K et al (2012) Preexposure prophylaxis for HIV infection among African women. N Engl J Med 367:411–422PubMedCentralPubMedGoogle Scholar
  105. 105.
    Microbicide Trials Network (2013) Daily HIV prevention approaches didn’t work for African women in the VOICE Study, AtlantaGoogle Scholar
  106. 106.
    Nowacek AS, Balkundi S, McMillan J, Roy U, Martinez-Skinner A, Mosley RL, Kanmogne G, Kabanov AV, Bronich T, Gendelman HE (2011) Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages. J Control Release 150:204–211PubMedCentralPubMedGoogle Scholar
  107. 107.
    Roy U, McMillan J, Alnouti Y et al (2012) Pharmacodynamic and antiretroviral activities of combination nanoformulated antiretrovirals in HIV-1-infected human peripheral blood lymphocyte-reconstituted mice. J Infect Dis. doi: 10.1093/infdis/jis395 Google Scholar
  108. 108.
    Brannon-Peppas L, Blanchette JO (2012) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 64:206–212Google Scholar
  109. 109.
    Gu FX, Karnik R, Wang AZ, Alexis F, Levy-Nissenbaum E, Hong S, Langer RS, Farokhzad OC (2007) Targeted nanoparticles for cancer therapy. Nano Today 2:14–21Google Scholar
  110. 110.
    Gunaseelan S, Gunaseelan K, Deshmukh M, Zhang X, Sinko PJ (2010) Surface modifications of nanocarriers for effective intracellular delivery of anti-HIV drugs. Adv Drug Deliv Rev 62:518–531PubMedCentralPubMedGoogle Scholar
  111. 111.
    Dahl V, Josefsson L, Palmer S (2010) HIV reservoirs, latency, and reactivation: prospects for eradication. Antiviral Res 85:286–294PubMedGoogle Scholar
  112. 112.
    Aquaro S, Caliò R, Balzarini J, Bellocchi MC, Garaci E, Perno CF (2002) Macrophages and HIV infection: therapeutical approaches toward this strategic virus reservoir. Antiviral Res 55:209–225PubMedGoogle Scholar
  113. 113.
    Dutta T, Garg M, Jain NK (2008) Targeting of efavirenz loaded tuftsin conjugated poly(propyleneimine) dendrimers to HIV infected macrophages in vitro. Eur J Pharm Sci 34:181–189PubMedGoogle Scholar
  114. 114.
    Collins KB, Patterson BK, Naus GJ, Landers DV, Gupta P (2000) Development of an in vitro organ culture model to study transmission of HIV-1 in the female genital tract. Nat Med 6:475PubMedGoogle Scholar
  115. 115.
    Das Neves J, Amiji MM, Bahia MF, Sarmento B (2010) Nanotechnology-based systems for the treatment and prevention of HIV/AIDS. Adv Drug Deliv Rev 62:458–477PubMedGoogle Scholar
  116. 116.
    Arnáiz B, Martínez-Ávila O, Falcon-Perez JM, Penadés S (2012) Cellular uptake of gold nanoparticles bearing HIV gp120 oligomannosides. Bioconjug Chem 23:814–825PubMedGoogle Scholar
  117. 117.
    Woodrow KA, Bennett KM, Lo DD (2012) Mucosal vaccine design and delivery. Annu Rev Biomed Eng 14:17–46PubMedGoogle Scholar
  118. 118.
    Lara HH, Ayala-Nuñez NV, Ixtepan-Turrent L, Rodriguez-Padilla C (2010) Mode of antiviral action of silver nanoparticles against HIV-1. J Nanobiotechnol 8:1Google Scholar
  119. 119.
    Hayakawa T, Kawamura M, Okamoto M, Baba M, Niikawa T, Takehara S, Serizawa T, Akashi M (1998) Concanavalin A-immobilized polystyrene nanospheres capture HIV-1 virions and gp120: potential approach towards prevention of viral transmission. J Med Virol 56:327–331PubMedGoogle Scholar
  120. 120.
    Leung V, Ko F (2011) Biomedical applications of nanofibers. Polym Adv Technol 22:350–365Google Scholar
  121. 121.
    Teo W-E, Inai R, Ramakrishna S (2011) Technological advances in electrospinning of nanofibers. Sci Technol Adv Mater 12:013002Google Scholar
  122. 122.
    Sill TJ, Von Recum HA (2008) Electrospinning: applications in drug delivery and tissue engineering. Biomaterials 29:1989–2006PubMedGoogle Scholar
  123. 123.
    Liang D, Hsiao BS, Chu B (2007) Functional electrospun nanofibrous scaffolds for biomedical applications. Adv Drug Deliv Rev 59:1392–1412PubMedCentralPubMedGoogle Scholar
  124. 124.
    Gunn J, Zhang M (2010) Polyblend nanofibers for biomedical applications: perspectives and challenges. Trends Biotechnol 28:189–197PubMedGoogle Scholar
  125. 125.
    Huang C, Soenen SJ, Rejman J, Lucas B, Braeckmans K, Demeester J, De Smedt SC (2011) Stimuli-responsive electrospun fibers and their applications. Chem Soc Rev 40:2417PubMedGoogle Scholar
  126. 126.
    Fridrikh S, Yu J, Brenner M, Rutledge G (2003) Controlling the fiber diameter during electrospinning. Phys Rev Lett. doi: 10.1103/PhysRevLett.90.144502 PubMedGoogle Scholar
  127. 127.
    Zhang K, Qian Y, Wang H, Fan L, Huang C, Yin A, Mo X (2010) Genipin-crosslinked silk fibroin/hydroxybutyl chitosan nanofibrous scaffolds for tissue-engineering application. J Biomed Mater Res A 95A:870–881Google Scholar
  128. 128.
    Teo W-E, He W, Ramakrishna S (2006) Electrospun scaffold tailored for tissue-specific extracellular matrix. Biotechnol J 1:918–929PubMedGoogle Scholar
  129. 129.
    Venugopal J, Ramakrishna S (2005) Applications of polymer nanofibers in biomedicine and biotechnology. Appl Biochem Biotechnol 125:147–158PubMedGoogle Scholar
  130. 130.
    Cao H, Mchugh K, Chew SY, Anderson JM (2010) The topographical effect of electrospun nanofibrous scaffolds on the in vivo and in vitro foreign body reaction. J Biomed Mater Res A 93(3):1151–1159PubMedGoogle Scholar
  131. 131.
    Yu D-G (2009) Electrospun nanofiber-based drug delivery systems. Health 01:67–75Google Scholar
  132. 132.
    Patel SK, Lavasanifar A, Choi P (2009) Roles of nonpolar and polar intermolecular interactions in the improvement of the drug loading capacity of PEO-b-PCL with increasing PCL content for two hydrophobic cucurbitacin drugs. Biomacromolecules 10:2584–2591PubMedGoogle Scholar
  133. 133.
    Heunis TDJ, Dicks LMT (2010) Nanofibers offer alternative ways to the treatment of skin infections. J Biomed Biotechnol 2010:1–11Google Scholar
  134. 134.
    Tiwari SK, Tzezana R, Zussman E, Venkatraman SS (2010) Optimizing partition-controlled drug release from electrospun core–shell fibers. Int J Pharm 392:209–217PubMedGoogle Scholar
  135. 135.
    Taepaiboon P, Rungsardthong U, Supaphol P (2007) Vitamin-loaded electrospun cellulose acetate nanofiber mats as transdermal and dermal therapeutic agents of vitamin A acid and vitamin E. Eur J Pharm Biopharm 67:387–397PubMedGoogle Scholar
  136. 136.
    Li X, Kanjwal MA, Lin L, Chronakis IS (2013) Electrospun polyvinyl-alcohol nanofibers as oral fast-dissolving delivery system of caffeine and riboflavin. Colloids Surf B Biointerfaces 103:182–188PubMedGoogle Scholar
  137. 137.
    Ignatious F, Sun L, Lee C-P, Baldoni J (2010) Electrospun nanofibers in oral drug delivery. Pharm Res 27:576–588PubMedGoogle Scholar
  138. 138.
    Bernards DA, Bhisitkul RB, Wynn P, Steedman MR, Lee O-T, Wong F, Thoongsuwan S, Desai TA (2013) Ocular biocompatibility and structural integrity of micro- and nanostructured poly(caprolactone) films. J Ocul Pharmacol Ther 29(2):249–57PubMedGoogle Scholar
  139. 139.
    Meinel AJ, Germershaus O, Luhmann T, Merkle HP, Meinel L (2012) Electrospun matrices for localized drug delivery: current technologies and selected biomedical applications. Eur J Pharm Biopharm 81:1–13PubMedGoogle Scholar
  140. 140.
    Huang C, Soenen SJ, Van Gulck E et al (2012) Electrospun cellulose acetate phthalate fibers for semen induced anti-HIV vaginal drug delivery. Biomaterials 33:962–969PubMedGoogle Scholar
  141. 141.
    Ball C, Krogstad E, Chaowanachan T, Woodrow KA (2012) Drug-eluting fibers for HIV-1 inhibition and contraception. PLoS One 7:e49792PubMedCentralPubMedGoogle Scholar
  142. 142.
    Cui W, Li X, Zhu X, Yu G, Zhou S, Weng J (2006) Investigation of drug release and matrix degradation of electrospun poly(dl-lactide) fibers with paracetanol inoculation. Biomacromolecules 7:1623–1629PubMedGoogle Scholar
  143. 143.
    Yohe ST, Colson YL, Grinstaff MW (2012) Superhydrophobic materials for tunable drug release: using displacement of air to control delivery rates. J Am Chem Soc 134:2016–2019PubMedGoogle Scholar
  144. 144.
    Zhang YZ, Wang X, Feng Y, Li J, Lim CT, Ramakrishna S (2006) Coaxial electrospinning of (fluorescein isothiocyanate-conjugated bovine serum albumin)-encapsulated poly(ε-caprolactone) nanofibers for sustained release. Biomacromolecules 7:1049–1057PubMedGoogle Scholar
  145. 145.
    Zamani M, Morshed M, Varshosaz J, Jannesari M (2010) Controlled release of metronidazole benzoate from poly ε-caprolactone electrospun nanofibers for periodontal diseases. Eur J Pharm Biopharm 75:179–185PubMedGoogle Scholar
  146. 146.
    Chunder A, Sarkar S, Yu Y, Zhai L (2007) Fabrication of ultrathin polyelectrolyte fibers and their controlled release properties. Colloids Surf B Biointerfaces 58:172–179PubMedGoogle Scholar
  147. 147.
    Zeng J, Aigner A, Czubayko F, Kissel T, Wendorff JH, Greiner A (2005) Poly(vinyl alcohol) nanofibers by electrospinning as a protein delivery system and the retardation of enzyme release by additional polymer coatings. Biomacromolecules 6:1484–1488PubMedGoogle Scholar
  148. 148.
    Yang Y, Li X, Qi M, Zhou S, Weng J (2008) Release pattern and structural integrity of lysozyme encapsulated in core–sheath structured poly(dl-lactide) ultrafine fibers prepared by emulsion electrospinning. Eur J Pharm Biopharm 69:106–116PubMedGoogle Scholar
  149. 149.
    Yu D-G, Zhu B-W, Yang W, Li Q (2011) Solid dispersions in the form of electrospun core-sheath nanofibers. Int J Nanomedicine 6:3271–3280Google Scholar
  150. 150.
    Yarin AL (2011) Coaxial electrospinning and emulsion electrospinning of core-shell fibers. Polym Adv Technol 22:310–317Google Scholar
  151. 151.
    Kenawy E-R, Abdel-Hay FI, El-Newehy MH, Wnek GE (2007) Controlled release of ketoprofen from electrospun poly(vinyl alcohol) nanofibers. Mater Sci Eng A 459:390–396Google Scholar
  152. 152.
    Jannesari M, Varshosaz J, Morshed M, Zamani M (2011) Composite poly(vinyl alcohol)/poly(vinyl acetate) electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs. Int J Nanomedicine 6:993–1003PubMedCentralPubMedGoogle Scholar
  153. 153.
    Xie J, Wang C-H (2006) Electrospun micro- and nanofibers for sustained delivery of paclitaxel to treat C6 glioma in vitro. Pharm Res 23:1817–1826PubMedGoogle Scholar
  154. 154.
    Mehta S, Verstraelen H, Peremans K, Villeirs G, Vermeire S, De Vos F, Mehuys E, Remon JP, Vervaet C (2012) Vaginal distribution and retention of a multiparticulate drug delivery system, assessed by gamma scintigraphy and magnetic resonance imaging. Int J Pharm 426:44–53PubMedGoogle Scholar
  155. 155.
    Macri LK, Sheihet L, Singer AJ, Kohn J, Clark RAF (2012) Ultrafast and fast bioerodible electrospun fiber mats for topical delivery of a hydrophilic peptide. J Control Release 161:813–820PubMedGoogle Scholar
  156. 156.
    Okuda T, Tominaga K, Kidoaki S (2010) Time-programmed dual release formulation by multilayered drug-loaded nanofiber meshes. J Control Release 143:258–264PubMedGoogle Scholar
  157. 157.
    Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD (1998) Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 338:853–860PubMedGoogle Scholar
  158. 158.
    Veazey RS, Ketas TJ, Dufour J, Moroney-Rasmussen T, Green LC, Klasse PJ, Moore JP (2010) Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor. J Infect Dis 202:739–744PubMedCentralPubMedGoogle Scholar
  159. 159.
    Prabaharan M, Jayakumar R, Nair SV (2011) Electrospun nanofibrous scaffolds-current status and prospects in drug delivery. In: Jayakumar R, Nair S (eds) Biomedical applications of polymeric nanofibers. Springer, Berlin, pp 241–262Google Scholar
  160. 160.
    Xu X, Chen X, Wang Z, Jing X (2009) Ultrafine PEG–PLA fibers loaded with both paclitaxel and doxorubicin hydrochloride and their in vitro cytotoxicity. Eur J Pharm Biopharm 72:18–25PubMedGoogle Scholar
  161. 161.
    Verreck G, Chun I, Peeters J, Rosenblatt J, Brewster ME (2003) Preparation and characterization of nanofibers containing amorphous drug dispersions generated by electrostatic spinning. Pharm Res 20:810–817PubMedGoogle Scholar
  162. 162.
    Yu D-G, Branford-White C, Shen X-X, Zhang X-F, Zhu L-M (2010) Solid dispersions of ketoprofen in drug-loaded electrospun nanofibers. J Dispers Sci Technol 31:902–908Google Scholar
  163. 163.
    Ham AS, Rohan LC, Boczar A, Yang L, Buckheit KW, Buckheit RW (2012) Vaginal film drug delivery of the pyrimidinedione IQP-0528 for the prevention of HIV infection. Pharm Res 29:1897–1907PubMedGoogle Scholar
  164. 164.
    Wang Y, Hsieh Y-L (2008) Immobilization of lipase enzyme in polyvinyl alcohol (PVA) nanofibrous membranes. J Membr Sci 309:73–81Google Scholar
  165. 165.
    Choi JS, Choi SH, Yoo HS (2011) Coaxial electrospun nanofibers for treatment of diabetic ulcers with binary release of multiple growth factors. J Mater Chem 21:5258Google Scholar
  166. 166.
    Liao I, Chen S, Liu J, Leong K (2009) Sustained viral gene delivery through core-shell fibers. J Control Release 139:48–55PubMedCentralPubMedGoogle Scholar
  167. 167.
    Saraf A, Baggett LS, Raphael RM, Kasper FK, Mikos AG (2010) Regulated non-viral gene delivery from coaxial electrospun fiber mesh scaffolds. J Control Release 143:95–103PubMedCentralPubMedGoogle Scholar
  168. 168.
    Cao H, Jiang X, Chai C, Chew SY (2010) RNA interference by nanofiber-based siRNA delivery system. J Control Release 144:203–212PubMedGoogle Scholar
  169. 169.
    Salalha W, Kuhn J, Dror Y, Zussman E (2006) Encapsulation of bacteria and viruses in electrospun nanofibres. Nanotechnology 17:4675–4681PubMedGoogle Scholar
  170. 170.
    Gensheimer M, Becker M, Brandis-Heep A, Wendorff JH, Thauer RK, Greiner A (2007) Novel biohybrid materials by electrospinning: nanofibers of poly(ethylene oxide) and living bacteria. Adv Mater 19:2480–2482Google Scholar
  171. 171.
    Townsend-Nicholson A, Jayasinghe SN (2006) Cell electrospinning: a unique biotechnique for encapsulating living organisms for generating active biological microthreads/scaffolds. Biomacromolecules 7:3364–3369PubMedGoogle Scholar
  172. 172.
    Maretschek S, Greiner A, Kissel T (2008) Electrospun biodegradable nanofiber nonwovens for controlled release of proteins. J Control Release 127:180–187PubMedGoogle Scholar
  173. 173.
    Chew SY, Wen J, Yim EK, Leong KW (2005) Sustained release of proteins from electrospun biodegradable fibers. Biomacromolecules 6(4):2017–2024PubMedGoogle Scholar
  174. 174.
    Patel S, Kurpinski K, Quigley R, Gao H, Hsiao BS, Poo M-M, Li S (2007) Bioactive nanofibers: synergistic effects of nanotopography and chemical signaling on cell guidance. Nano Lett 7:2122–2128PubMedGoogle Scholar
  175. 175.
    Beck-Broichsitter M, Thieme M, Nguyen J, Schmehl T, Gessler T, Seeger W, Agarwal S, Greiner A, Kissel T (2010) Novel “nano in nano” composites for sustained drug delivery: biodegradable nanoparticles encapsulated into nanofiber non-wovens. Macromol Biosci 10:1527–1535PubMedGoogle Scholar
  176. 176.
    Zomer Volpato F, Almodóvar J, Erickson K, Popat KC, Migliaresi C, Kipper MJ (2012) Preservation of FGF-2 bioactivity using heparin-based nanoparticles, and their delivery from electrospun chitosan fibers. Acta Biomater 8:1551–1559PubMedGoogle Scholar
  177. 177.
    Chen M, Gao S, Dong M, Song J, Yang C, Howard KA, Kjems J, Besenbacher F (2012) Chitosan/siRNA nanoparticles encapsulated in PLGA nanofibers for siRNA delivery. ACS Nano 6:4835–4844PubMedGoogle Scholar
  178. 178.
    Yoo HS, Kim TG, Park TG (2009) Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery. Adv Drug Deliv Rev 61:1033–1042PubMedGoogle Scholar
  179. 179.
    Agarwal S, Wendorff JH, Greiner A (2010) Chemistry on electrospun polymeric nanofibers: merely routine chemistry or a real challenge? Macromol Rapid Commun 31:1317–1331PubMedGoogle Scholar
  180. 180.
    El-Sadr WM, Mayer KH, Maslankowski L et al (2006) Safety and acceptability of cellulose sulfate as a vaginal microbicide in HIV-infected women. AIDS 20:1109–1116PubMedGoogle Scholar
  181. 181.
    Puttipaiboon N, Yoovidhya T, Wongsasulak S (2012) Fabrication and gastro-mucoadhesive property of Zein-PEO-Chitosan blend ultrafine fibrous films. Proc NanoThailand 2012:13–16Google Scholar
  182. 182.
    Johnson TJ, Gupta KM, Fabian J, Albright TH, Kiser PF (2010) Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir. Eur J Pharm Sci 39:203–212PubMedGoogle Scholar
  183. 183.
    Major I, Boyd P, Kilbourne-Brook M, Saxon G, Cohen J (2013) Malcolm RK A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine. Contraception 88(1):58–66. doi: 10.1016/j.contraception.2012.10.018 PubMedGoogle Scholar
  184. 184.
    Yoo J-W, Dharmala K, Lee CH (2006) The physicodynamic properties of mucoadhesive polymeric films developed as female controlled drug delivery system. Int J Pharm 309:139–145PubMedGoogle Scholar
  185. 185.
    Baji A, Mai Y-W, Wong S-C, Abtahi M, Chen P (2010) Electrospinning of polymer nanofibers: effects on oriented morphology, structures and tensile properties. Compos Sci Technol 70:703–718Google Scholar
  186. 186.
    Ayutsede J, Gandhi M, Sukigara S, Ye H, Hsu C, Gogotsi Y, Ko F (2006) Carbon nanotube reinforced Bombyx mori silk nanofibers by the electrospinning process. Biomacromolecules 7:208–214PubMedGoogle Scholar
  187. 187.
    Katta P, Alessandro M, Ramsier RD, Chase GG (2004) Continuous electrospinning of aligned polymer nanofibers onto a wire drum collector. Nano Lett 4:2215–2218Google Scholar
  188. 188.
    Li W-J, Mauck RL, Cooper JA, Yuan X, Tuan RS (2007) Engineering controllable anisotropy in electrospun biodegradable nanofibrous scaffolds for musculoskeletal tissue engineering. J Biomech 40:1686–1693PubMedCentralPubMedGoogle Scholar
  189. 189.
    Wang S, Zhang Y, Yin G, Wang H, Dong Z (2009) Electrospun polylactide/silk fibroin–gelatin composite tubular scaffolds for small-diameter tissue engineering blood vessels. J Appl Polym Sci 113:2675–2682Google Scholar
  190. 190.
    Kidoaki S, Kwon IK, Matsuda T (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 26:37–46PubMedGoogle Scholar
  191. 191.
    Pham QP, Sharma U, Mikos AG (2006) Electrospun poly(ε-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules 7:2796–2805PubMedGoogle Scholar
  192. 192.
    McClure MJ, Sell SA, Simpson DG, Walpoth BH, Bowlin GL (2010) A three-layered electrospun matrix to mimic native arterial architecture using polycaprolactone, elastin, and collagen: a preliminary study. Acta Biomater 6:2422–2433PubMedGoogle Scholar
  193. 193.
    Teo WE, Kotaki M, Mo XM, Ramakrishna S (2005) Porous tubular structures with controlled fibre orientation using a modified electrospinning method. Nanotechnology 16:918–924Google Scholar
  194. 194.
    Van Lieshout MI, Vaz CM, Rutten MCM, Peters GWM, Baaijens FPT (2006) Electrospinning versus knitting: two scaffolds for tissue engineering of the aortic valve. J Biomater Sci Polym Ed 17:77–89PubMedGoogle Scholar
  195. 195.
    Del Gaudio C, Grigioni M, Bianco A, De Angelis G (2008) Electrospun bioresorbable heart valve scaffold for tissue engineering. Int J Artif Organs 31:68–75PubMedGoogle Scholar
  196. 196.
    Szentivanyi A, Chakradeo T, Zernetsch H, Glasmacher B (2011) Electrospun cellular microenvironments: understanding controlled release and scaffold structure. Adv Drug Deliv Rev 63:209–220PubMedGoogle Scholar
  197. 197.
    Food and Agricultural Organization of the United Nations AIDS—a threat to rural Africa. Accessed 16 Jan 2013
  198. 198.
    Kayaci F, Uyar T (2012) Encapsulation of vanillin/cyclodextrin inclusion complex in electrospun polyvinyl alcohol (PVA) nanowebs: prolonged shelf-life and high temperature stability of vanillin. Food Chem 133:641–649Google Scholar
  199. 199.
    Greiner A, Wendorff JH (2007) Electrospinning: a fascinating method for the preparation of ultrathin fibers. Angew Chem Int Ed 46:5670–5703Google Scholar
  200. 200.
    Xia X, Dong XJ, Wei QF, Cai YB, Lu KY (2011) Formation mechanism of porous hollow SnO2 nanofibers prepared by one-step electrospinning. Express Polym Lett 6:169–176Google Scholar
  201. 201.
    Mauck RL, Baker BM, Nerurkar NL, Burdick JA, Li W-J, Tuan RS, Elliott DM (2009) Engineering on the straight and narrow: the mechanics of nanofibrous assemblies for fiber-reinforced tissue regeneration. Tissue Eng Part B Rev 15:171–193PubMedCentralPubMedGoogle Scholar

Copyright information

© Controlled Release Society 2014

Authors and Affiliations

  • Emily A. Krogstad
    • 1
  • Michael J. Rathbone
    • 2
  • Kim A. Woodrow
    • 1
  1. 1.Department of BioengineeringUniversity of WashingtonSeattleUSA
  2. 2.School of PharmacyInternational Medical UniversityKuala LumpurMalaysia

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