Skip to main content

Advertisement

SpringerLink
Log in

Thermosensitive hydrogel of hydrophobically-modified methylcellulose for intravaginal drug delivery

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Hydrogels with the advantages of prolonging drug release and administration convenience are necessary for intravaginal drug delivery to prevent sexual transmission of human immunodeficiency virus and other vaginal infections. In this study, the thermosensitive hydrogel of methylcellulose modified by stearic acid (MCS) were evaluated in the presence of NaCl and phosphates, which exhibited sol-to-gel transition performance at body temperature or even lower. The in vitro cytotoxicity and in vivo mucosal irritation were investigated and the results showed that MCS hydrogel possessed good biocompatibility similar with hydroxyethyl cellulose (HEC) gel. Significantly, the release studies revealed that MCS hydrogel could control tenofovir sustained release for 10 h without burst release, longer than that from HEC gel or poloxamer 407 hydrogel. Therefore, MCS thermosensitive hydrogel would be a promising carrier for intravaginal delivery of antiviral drugs for long time controlled release.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. UN AIDS/WHO, 2010. AIDS Epidemic: July 2010.

  2. Ndesendo VMK, Pillay V, Choonara YE, Buchmann E, Bayever DN, Meyer LCR. A review of current intravaginal drug delivery approaches employed for the prophylaxis of HIV/AIDS and prevention of sexually transmitted infections. AAPS PharmSciTech. 2008;9:505–20.

    Article  CAS  Google Scholar 

  3. Krishnan S, Dunbar MS, Minnis AM, Medlin CA, Gerdts CE, Padian NS. Poverty, gender inequities, and women’s risk of human immunodeficiency virus/AIDS. Ann N Y Acad Sci. 2008;1136:101–10.

    Article  Google Scholar 

  4. Brown TJ, Yen-Moore A, Trying SK. An overview of sexually transmitted diseases. Part 1. J Am Acad Dermatol. 1999;41:511–32.

    CAS  Google Scholar 

  5. Lisa CR, Alexandra BS. Vaginal drug delivery systems for HIV prevention. AAPS J. 2009;11:78–87.

    Article  Google Scholar 

  6. Bourinbaiar AS, Root-Bernstein RS, Abulafia-Lapid R, Rytik PG, Kanev V, Jirathitikal AN, Orlovsky VG. Therapeutic AIDS vaccines. Curr Pharm Des. 2006;12:2017–30.

    Article  CAS  Google Scholar 

  7. Cutler B, Justman J. Vaginal microbicides and the prevention of HIV transmission. Lancet Infect Dis. 2008;8:685–97.

    Article  CAS  Google Scholar 

  8. Weber J, Desai K, Darbyshire J. The development of vaginal microbicides for the prevention of HIV transmission. PLoS Med. 2005;2:392–5.

    Article  Google Scholar 

  9. Vermani K, Garg S. The scope and potential of vaginal drug delivery. Pharm Sci Techol Today. 2000;3:359–64.

    Article  CAS  Google Scholar 

  10. Hussain A, Ahsan F. The vagina as a route for systemic drug delivery. J Control Release. 2005;103:301–13.

    Article  CAS  Google Scholar 

  11. Valenta C. The use of mucoadhesive polymers in vaginal delivery. Adv Drug Deliv Rev. 2005;57:1692–712.

    Article  CAS  Google Scholar 

  12. Bilensoy E, Rouf AM, Vural I, Sen M, Hincal AA. Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole cyclodextrin complex. AAPS PharmSciTech. 2006;7:1–13.

    Article  Google Scholar 

  13. das Neves J, Bahia MF. Gels as vaginal drug delivery systems. Int J Pharm. 2006;318:1–14.

    Article  Google Scholar 

  14. Liu J, Zhang SM, Chen PP, Cheng L, Zhou W, Tang WX, Chen ZW, Ke CM. Controlled release of insulin from PLGA nanoparticles embedded within PVA hydrogels. J Mater Sci Mater Med. 2007;18:2205–10.

    Article  CAS  Google Scholar 

  15. Gaetano FD, Ambrosio L, Raucci MG, Marotta A, Catauro M. Sol–gel processing of drug delivery materials and release kinetics. J Mater Sci Mater Med. 2005;16:261–5.

    Article  CAS  Google Scholar 

  16. Kang YM, Kim GH, Kim J, Kim DY, Lee BN, Yoon SM, Kim JH, Kim MS. In vivo efficacy of an intratumorally injected in situ-forming doxorubicin/poly-(ethylene glycol)-b-polycaprolactone diblock copolymer. Biomaterials. 2011;32:4556–64.

    Article  CAS  Google Scholar 

  17. Feeney M, Casadei MA, Matricardi P. Carboxymethyl derivative of scleroglucan: a novel thermosensitive hydrogel forming polysaccharide for drug delivery applications. J Mater Sci Mater Med. 2009;20:1081–7.

    Article  CAS  Google Scholar 

  18. Knuth K, Amiji M, Robinson JR. Hydrogel delivery systems for vaginal and oral applications: formulation and biological considerations. Adv Drug Deliv Rev. 1993;11:137–67.

    Article  Google Scholar 

  19. Zhou WJ, Zhao M, Zhao Y, Mou Y. A fibrin gel loaded with chitosan nanoparticles for local delivery of rhEGF: preparation and in vitro release studies. J Mater Sci Mater Med. 2011;22:1221–30.

    Article  Google Scholar 

  20. Yool J-W, Giri N, Lee CH. pH-sensitive Eudragit nanoparticles for mucosal drug delivery. Int J Pharm. 2010;403:262–7.

    Google Scholar 

  21. Buckheit RW Jr. Development of topical microbicides to prevent the sexual transmission of HIV. Antivir Res. 2010;85:142–58.

    Article  CAS  Google Scholar 

  22. Schwartz JL, Ballagh SA, Kwok C, Mauck CK, Weiner DH, Rencher WF, Callahan MM. Fourteen-day safety and acceptability study of the universal placebo gel. Contraception. 2007;75:136–41.

    Article  Google Scholar 

  23. Mahalingam A, Smith E, Fabian J, Damian FR, Peters JJ, Clark MR, Friend DR, Katz DF, Kiser PF. Design of a semisolid vaginal microbicide gel by relating composition to properties and performance. Pharm Res. 2010;27:2478–91.

    Article  CAS  Google Scholar 

  24. Xu Y, Li L. Thermoreversible and salt-sensitive turbidity of methylcellulose in aqueous solution. Polymer. 2005;46:7410–7.

    Article  CAS  Google Scholar 

  25. Hirrien M, Chevillard C, Desbrièresa J, Axelos MAV, Rinaudo M. Thermogelation of methylcelluloses: new evidence for understanding the gelation mechanism. Polymer. 1998;25:6251–9.

    Article  Google Scholar 

  26. Lee SC, Cho YW, Park K. Control of thermogelation properties of hydrophobically-modified methylcellulose. J Bioact Compat Pol. 2005;20:5–13.

    Article  CAS  Google Scholar 

  27. Tien D, Schnaare RL, Kang F, Cohl G, Mccormick TJ, Moench TR, Doncel G, Douville K, Romano JW. In vitro and in vivo characterization of a potential universal placebo designed for use in vaginal microbicide clinical trials. Aids Res Hum Retrov. 2005;21:845–53.

    Article  CAS  Google Scholar 

  28. Ji QX, Chen XG, Zhao QS, Liu CS, Cheng XJ, Wang LC. Injectable thermosensitive hydrogel based on chitosan and quaternized chitosan and the biomedical properties. J Mater Sci Mater Med. 2009;20:1603–10.

    Article  CAS  Google Scholar 

  29. Aranha CC, Gupta SM, Reddy KVR. Assessment of cervicovaginal cytokine levels following exposure to microbicide Nisin gel in rabbits. Cytokine. 2008;43:63–70.

    Article  CAS  Google Scholar 

  30. Desbrièresa J, Hirriena M, Ross-Murphy SB. Thermogelation of methylcellulose: rheological considerations. Polymer. 2000;41:2451–61.

    Article  Google Scholar 

  31. Kenneth HM, Lisa AM. Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women. AIDS. 2006;20:543–51.

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the National High Technology Research and Development Program of China (863) (2009AA03Z313) and National Grand Program on Key Infectious Disease Control (2008ZX10001-015-10).

Author information

Authors and Affiliations

  1. Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, No. 92, Weijin Road, Nankai District, Tianjin, 300072, People’s Republic of China

    Ning Li, Meihua Yu, Liandong Deng & Anjie Dong

  2. The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, People’s Republic of China

    Jun Yang

Authors
  1. Ning Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meihua Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liandong Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anjie Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anjie Dong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, N., Yu, M., Deng, L. et al. Thermosensitive hydrogel of hydrophobically-modified methylcellulose for intravaginal drug delivery. J Mater Sci: Mater Med 23, 1913–1919 (2012). https://doi.org/10.1007/s10856-012-4664-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4664-9

Keywords

Search

Navigation