Transdermal Delivery of Luteinizing Hormone-releasing Hormone with Chitosan Microneedles: A Promising Tool for Androgen Deprivation Therapy

Anticancer Res. 2017 Dec;37(12):6791-6797. doi: 10.21873/anticanres.12139.

Abstract

Long-term administration of luteinizing hormone-releasing hormone analogs (LHRHa) is the main type of androgen-deprivation therapy (ADT) for lethal prostate cancer. A fully insertable microneedle system, composed of embeddable chitosan microneedles and a dissolvable polyvinyl alcohol/polyvinyl pyrrolidone supporting array, was developed for sustained delivery of LHRHa to the skin. A porcine cadaver skin test showed that chitosan microneedles can be fully embedded within the skin and microneedle-created micropores reseal within 7 days. The measured LHRHa loading amount was 73.3±2.8 μg per microneedle patch. After applying goserelin-containing microneedles to mice, serum LH levels increased initially and then declined below baseline at day 7. In contrast, serum testosterone levels increased to reach a peak at day 14 and then declined to a castration level at day 21. Additionally, such a castration level was maintained for 2 weeks. Therefore, transdermal delivery of goserelin with embeddable chitosan microneedles can produce a castrated state in mice. Such a system is a promising, feasible means of delivering ADT.

Keywords: Prostate cancer; chitosan; microneedle; testosterone.

MeSH terms

  • Administration, Cutaneous
  • Androgen Antagonists / administration & dosage*
  • Androgen Antagonists / chemistry
  • Androgen Antagonists / pharmacokinetics
  • Animals
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / chemistry
  • Antineoplastic Agents, Hormonal / pharmacokinetics
  • Chitosan / chemistry*
  • Drug Delivery Systems / methods*
  • Gonadotropin-Releasing Hormone / administration & dosage*
  • Gonadotropin-Releasing Hormone / chemistry
  • Gonadotropin-Releasing Hormone / pharmacokinetics
  • Goserelin / administration & dosage
  • Goserelin / chemistry
  • Goserelin / pharmacokinetics
  • Humans
  • Luteinizing Hormone / blood
  • Male
  • Mice, Inbred ICR
  • Needles*
  • Skin / metabolism
  • Swine
  • Testosterone / blood

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Goserelin
  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Luteinizing Hormone
  • Chitosan