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

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 mu g 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.