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  • Original Article
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Delivery of intracavernosal therapies using needle-free injection devices

Abstract

ED affects a significant proportion of males worldwide. With an ever-aging population the prevalence of ED is predicted to double in the next decade. Oral PDE-5 inhibitors are the first-line treatment for ED and have revolutionised its management. These agents are however ineffective in some men. Intracavernosal injection (ICI) of vasoactive agents is an effective second-line therapy for ED. Despite proven efficacy, needle phobia and anxiety with self-needling limit the use of intracavernosal (IC) therapies. Needle-free injection (NFI) devices allow delivery of parenteral therapies through the skin, without a needle. Although these devices have been available for decades, early studies investigating their use for ICI showed inferiority compared to standard needle-tip syringe delivery. Advances in engineering of these systems have lead to functional improvements of many aspects of fluid delivery. Our research demonstrates that modern NFI devices are better equipped to deliver ICI, and, in the cadaver models examined, achieved successful IC delivery. These findings support the potential feasibility of NFI devices to deliver ICI, and may broaden the utility of these devices to patients who refuse or discontinue IC therapy because of needle phobia or other issues with standard needle-tip syringes.

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References

  1. Lue TF . Erectile dysfunction. N Engl J Med 2000; 342: 1802–1813.

    Article  CAS  Google Scholar 

  2. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB . Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54–61.

    Article  CAS  Google Scholar 

  3. Ayta IA, McKinlay JB, Krane RJ . The likely worldwide increase in erectile dysfunction between 1995 and 2025 and some possible policy consequences. BJU Int 1999; 84: 50–56.

    Article  CAS  Google Scholar 

  4. Eardley I, Donatucci C, Corbin J, El-Meliegy A, Hatzimouratidis K, McVary K et al. Pharmacotherapy for erectile dysfunction. J Sex Med 2010; 7: 524–540.

    Article  CAS  Google Scholar 

  5. Hatzimouratidis K, Hatzichristou DG . A comparative review of the options for treatment of erectile dysfunction: which treatment for which patient? Drugs 2005; 65: 1621–1650.

    Article  CAS  Google Scholar 

  6. McMahon CN, Smith CJ, Shabsigh R . Treating erectile dysfunction when PDE5 inhibitors fail. BMJ 2006; 332: 589–592.

    Article  Google Scholar 

  7. Masson P, Lambert SM, Brown M, Shabsigh R . PDE-5 inhibitors: current status and future trends. Urol Clin North Am 2005; 32: 511–525.

    Article  Google Scholar 

  8. Shabsigh R, Padma-Nathanb H, Gittlemanc M, McMurray J, Kaufmane J, Goldstein I . Intracavernous alprostadil alfadex (EDEX/VIRIDAL) is effective and safe in patients with erectile dysfunction after failing sildenafil (Viagra). Urology 2000; 55: 477–480.

    Article  CAS  Google Scholar 

  9. Brannigan RE, Spitz A, Schatte EC, Orejuela FJ, Lipshultz LI, Kim ED . Comparison of sildenafil citrate (Viagra) versus trimix intracavernosal injection (ICI) as treatment for erectile dysfunction (ED). J Urol 1999; 161: 214.

    Article  Google Scholar 

  10. Lin JS, Lin YM, Jou YC, Cheng JT . Role of cyclic adenosine monophosphate in prostaglandin E1-induced penile erection in rabbits. Eur Urol 1995; 28: 259–265.

    Article  CAS  Google Scholar 

  11. Porst H . Current perspectives on intracavernosal pharmacotherapy for erectile dysfunction. Int J Impot Res 2000; 12 (Suppl 4): S91–S100.

    Article  Google Scholar 

  12. Nelson CJ, Hsiao W, Balk E, Narus J . Injection anxiety and pain in men using intracavernosal injection therapy after radical pelvic surgery. J Sex Med 2013; 10: 2559–2565.

    Article  Google Scholar 

  13. Van Driel MP, Mooibroek JJ, van de Wiel HBM, Mensink HGA . Intracavernosal pharmacotherapy: psychological, sexological and medical aspects. Int J Impot Res 1991; 3: 95–104.

    Google Scholar 

  14. Polito M, d ’Anzeo G, Conti A, Muzzonigro G . Erectile rehabilitation with intracavernous alprostadil after radical prostatectomy: refusal and dropout rates. BJU Int 2012; 110: E954–E957.

    Article  CAS  Google Scholar 

  15. Rowland DL, Boedhoe HSM, Dohle G, Slob AK . Intracavernosal self-injection therapy in men with erectile dysfunction: Satisfaction and attrition in 119 patients. Int J Impot Res 1999; 11: 145–151.

    Article  CAS  Google Scholar 

  16. McAllister L, Anderson J, Werth K, Cho I, Copeland K, Le Cam N et al. Needle-free jet injection for administration of influenza vaccine: a randomised non-inferiority trial. Lancet 2014; 384: 674–681.

    Article  Google Scholar 

  17. Ravi AD, Sadhna D, Nagpaal D, Chawla L . Needle free injection technology: a complete insight. Int J Pharm Investig 2015; 5: 192–199.

    Article  CAS  Google Scholar 

  18. Giudice EL, Campbell JD . Needle-free vaccine delivery. Adv Drug Deliv Rev 2006; 58: 68–89.

    Article  CAS  Google Scholar 

  19. Engwerda EE, Abbink EJ, Tack CJ, de Galan BE . Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care 2011; 34: 1804–1808.

    Article  CAS  Google Scholar 

  20. Halle J, Lambert J, Lindmayer I, Menassa K, Coutu F, Moghrabi A et al. Twice daily mixed regular and NPH insulin injections with new jet injector versus conventional syringes: pharmacokinetics of insulin absorption. Diabetes Care 1986; 9: 279–282.

    Article  CAS  Google Scholar 

  21. Harding LM, Adeniyi A, Everson R, Barker S, Ralph DJ, Baranowski AP . Comparison of a needle-free high-pressure injection system with needle-tipped injection of intracavernosal alprostadil for erectile dysfunction. Int J Impot Res 2002; 14: 498–501.

    Article  CAS  Google Scholar 

  22. Mitragotri S . Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov 2006; 5: 543–548.

    Article  Google Scholar 

  23. Jimenez N, Bradford H, Seidel KD, Sousa M, Lynn AM . A comparison of a needle-free injection system for local anesthesia versus EMLA for intravenous catheter insertion in the pediatric patient. Anesth Analg 2006; 102: 411–414.

    Article  Google Scholar 

  24. Christensen MS, Hargens CW, Nacht S, Gans EH . Viscoelastic properties of intact human skin: instrumentation, hydration effects, and the contribution of the stratum corneum. J Invest Dermatol 1977; 69: 282–286.

    Article  CAS  Google Scholar 

  25. Schramm J, Mitragotri S . Transdermal drug delivery by jet injectors: energetics of jet formation and penetration. Pharm Res 2002; 19: 1673–1679.

    Article  CAS  Google Scholar 

  26. Shergold OA, Fleck NA, King TS . The penetration of a soft solid by a liquid jet, with application to the administration of a needle-free injection. J Biomech 2006; 39: 2593–2602.

    Article  Google Scholar 

  27. Casabe A, Bechara A, Cheliz G, Romano S, Rey H, Fredotovich N . Drop-out reasons and complications in self-injection therapy with a triple vasoactive drug mixture in sexual erectile dysfunction. Int J Impot Res 1998; 10: 5–9.

    Article  CAS  Google Scholar 

  28. McCabe MP, Althof SE . A systematic review of the psychosocial outcomes associated with erectile dysfunction: does the impact of erectile dysfunction extend beyond a man's inability to have sex? J Sex Med 2014; 11: 347–363.

    Article  Google Scholar 

  29. Sung HH, Ahn JS, Kim JJ, Choo SH, Han DH, Lee SW . The role of intracavernosal injection therapy and the reasons of withdrawal from therapy in patients with erectile dysfunction in the era of PDE5 inhibitors. Andrology 2014; 2: 45–50.

    Article  CAS  Google Scholar 

  30. Hamilton JG . Needle phobia: a neglected diagnosis. J Fam Pract 1995; 41: 169–175.

    CAS  Google Scholar 

  31. Hassan HA, Tohid H, Amin RM, Bidin MBL, Muthupalaniappen L, Omar K . Factors influencing insulin acceptance among type 2 diabetes mellitus patients in a primary care clinic: a qualitative exploration. BMC Fam Pract 2013; 14: 164.

    Article  Google Scholar 

  32. Larkin ME, Capasso VA, Chen CL, Mahoney EK, Hazard B, Cagliero E et al. Measuring psychological insulin resistance: barriers to insulin use. Diabetes Educ 2008; 34: 511–517.

    Article  Google Scholar 

  33. Mohr DC, Cox D, Epstein L, Boudewyn A . Teaching patients to selfinject: pilot study of a treatment for injection anxiety and phobia in multiple sclerosis patients prescribed injectable medication. J Behav Ther Exp Psychiatry 2002; 33: 39–47.

    Article  Google Scholar 

  34. Althof SE, Turner LA, Levine SB, Risen C, Kursh E, Bodner D et al. Why do so many people drop out from auto-injection therapy for impotence? J Sex Marital Ther 1989; 15: 121–129.

    Article  CAS  Google Scholar 

  35. Park JR, Kim CI, Park CH . Efficacy, satisfaction, and drop-out rate of alprostadil (prostagladin E1) intracavernosal injection according to etiologic cause of erectile dysfunction. Korean J Androl 1999; 17: 111–115.

    Google Scholar 

  36. Schoubbena A, Cavicchib A, Barberinic L, Faraond A, Bertid M, Riccia M et al. Dynamic behavior of a spring-powered micronozzle needle-free injector. Int J Pharm 2015; 491: 91–98.

    Article  Google Scholar 

  37. O’Kane D, Gibson L, Davidson A, Lawrentschuk N . MP-13.08: Needle-free delivery of intracavernosal injections: proof of concept. World J Urol 2015; 33: 62.

    Google Scholar 

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Acknowledgements

Preliminary data from the animal experiments in this manuscript were presented at the 35th Congress of the Société Internationale d’Urologie, and the accompanying conference abstract has been published.

Disclosure

The devices used in this research were supplied, on loan, by Meditrend International, VIC, Australia.

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Correspondence to D O'Kane.

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O'Kane, D., Gibson, L., du Plessis, J. et al. Delivery of intracavernosal therapies using needle-free injection devices. Int J Impot Res 29, 225–228 (2017). https://doi.org/10.1038/ijir.2017.27

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