Skip to main content

Advertisement

Log in

Potential of Sonophoresis as a Skin Penetration Technique in the Treatment of Rheumatoid Arthritis with Transdermal Patch

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis, a chronic disorder, limits the use of chemical penetration enhancers for a prolonged period of time. Moreover, systemic routes of administration of the first-line drug, methotrexate, have shown undesirable systemic as well as local side effects. The objective of this research was to overcome the limitations associated with treatment of rheumatoid arthritis by utilizing three physical transdermal penetration enhancement techniques namely cold-laser, electroporation, and sonophoresis to deliver methotrexate. Methotrexate patch was prepared using solvent casting method and the ex-vivo release of methotrexate in combination with three physical penetration enhancers (sonophoresis, electroporation, and cold laser) were studied. The best technique was employed in pre-clinical testing in arthritic and control groups of male Wistar rats excluding remaining two techniques. The comparative ex-vivo studies showed that the penetration enhancement of methotrexate is maximum by sonophoresis followed by electroporation and cold laser (sonophoresis > electroporation > cold laser). In pharmacodynamic studies, the reduction in diameter of injected and non-injected paw on day 5 and day 21 for group 4 (ultrasound pre-treated group) was higher as compared to group 3 (group receiving only methotrexate patch). The motility score and the reduction in pain were significantly improved for group 4 than group 3 on both day 5 and day 21 (P ˂ 0.05) which confirmed the faster recovery of animals of group 4 due to penetration enhancement of methotrexate patch by ultrasound treatment. From the results, it can be concluded that sonophoresis along with methotrexate patch has shown a significant effect in the treatment of rheumatoid arthritis.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Amarji B, Garg NK, Singh B, Katare OP. Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics. J Drug Target. 2016;7:147–60.

    Article  Google Scholar 

  2. Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010;376:1094–108.

    Article  Google Scholar 

  3. Smolen JS, Aletaha D, Bijlsma JW, Breedveld FC, Boumpas D, Burmester G, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2010;69:631–7.

    Article  Google Scholar 

  4. Shende P, Vaidya J, Gaud RS. Pharmacotherapeutic approaches for transportation of anticancer agents via skin artificial cells. Nanomed Biotechnol. 2018:1–11.

  5. Bathon JM, Martin RW, Fleischmann RM, Tesser JR, Schiff MH, Keystone EC, et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med. 2000;343:1586–93.

    Article  CAS  Google Scholar 

  6. Smolen JS, Han C, Bala M, Maini RN, Kalden JR, Van der Heijde D, et al. Evidence of radiographic benefit of treatment with infliximab plus methotrexate in rheumatoid arthritis patients who had no clinical improvement: a detailed subanalysis of data from the anti–tumor necrosis factor trial in rheumatoid arthritis with concomitant therapy study. Arthritis Rheum. 2005;52:1020–30.

    Article  CAS  Google Scholar 

  7. Brown MB, Traynor MJ, Martin GP, Akomeah FK. Transdermal drug delivery systems: skin perturbation devices. Drug Deliv Syst. 2008;437:119–39.

    Article  CAS  Google Scholar 

  8. Balaji P, Thirumal M, Gowri R, Divya V, Ramaswamy V. Design and evaluation of matrix type of transdermal patches of methotrexate. Int J Pharm Chem Biol Sci. 2012;2:464–71.

    CAS  Google Scholar 

  9. Noboru K, Mitsuhiro O, Yusuke S, Yoshimitsu A. Anti-inflammatory activities of light emitting diode irradiation on collagen-induced arthritis in mice (a secondary publication). Laser Therapy. 2014;23:191–9.

    Article  Google Scholar 

  10. Lee WR, Shen SC, Fang CL, Zhuo RZ, Fang JY. Topical delivery of methotrexate via skin pretreated with physical enhancement techniques: low-fluence erbium: YAG laser and electroporation. Lasers Surg Med. 2008;40:468–76.

    Article  Google Scholar 

  11. Brosseau L, Welch V, Wells GA, de Bie R, Gam A, Harman K, et al. Low level laser therapy (classes I, II and III) for treating rheumatoid arthritis. Cochrane Libr. 2005;19:CD002049.

    Google Scholar 

  12. Taudorf EH, Lerche CM, Vissing AC, Philipsen PA, Hannibal J, D’Alvise J, et al. Topically applied methotrexate is rapidly delivered into skin by fractional laser ablation. Expert Opin Drug Deliv. 2015;12:1059–69.

    Article  CAS  Google Scholar 

  13. Asano J, Suisha F, Takada M, Kawasaki N, Miyazaki S. Effect of pulsed output ultrasound on the transdermal absorption of indomethacin from an ointment in rats. Biol Pharm Bull. 1997;20:288–91.

    Article  CAS  Google Scholar 

  14. Wong TW, Chen CH, Huang CC, Lin CD, Hui SW. Painless electroporation with a new needle-free microelectrode array to enhance transdermal drug delivery. J Control Release. 2006;110:557–65.

    Article  CAS  Google Scholar 

  15. Kulkarni YA, Gokhale SB, Veeranjaneyulu A, Surana SJ, Tatiya AU. Effect of Perseamacrantha against acute inflammation and adjuvant-induced arthritis in rats. Pharm Biol. 2009;47:304–8.

    Article  Google Scholar 

  16. Kothavade PS, Bulani VD, Nagmoti V, Deshpande PS, Gawali NB, Juvekar AR. Therapeutic effect of saponin rich fraction of Achyranthesaspera Linn. on adjuvant-induced arthritis in Sprague-Dawley rats. Autoimmune Dis. 2015:943645.

  17. Vogel H. Drug discovery and evaluation: pharmacological assays. Springer Science & Business Media. 2007.

  18. Chadha PR, Arora R, Kaur A, Saini M, Singla D, Jain DS. Characterization of solvatomorphs of methotrexate using thermoanalytical and other techniques. Acta Pharma. 2009;59:245–57.

    CAS  Google Scholar 

  19. Oberli MA, Schoellhammer CM, Langer R, Blankschtein D. Ultrasound-enhanced transdermal delivery: recent advances and future challenges. Ther Deliv. 2014;5:843–57.

    Article  CAS  Google Scholar 

  20. Terahara T, Mitragotri S, Langer R. Porous resins as a cavitation enhancer for low-frequency sonophoresis. J Pharm Sci. 2002;91:753–9.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Pravin Shende.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vaidya, J., Shende, P. Potential of Sonophoresis as a Skin Penetration Technique in the Treatment of Rheumatoid Arthritis with Transdermal Patch. AAPS PharmSciTech 21, 180 (2020). https://doi.org/10.1208/s12249-020-01725-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-020-01725-w

KEY WORDS

Navigation