Novel iontophoretic administration method for local therapy of breast cancer

J Control Release. 2013 Jun 28;168(3):298-306. doi: 10.1016/j.jconrel.2013.03.021. Epub 2013 Apr 4.

Abstract

Ductal drug therapy is a novel therapeutic approach for primary breast cancers, particularly those involving ductal carcinoma in situ lesions. Total or partial mastectomy with or without radiotherapy is the standard local therapy for primary breast cancer. Here, we propose a novel drug administration method for ductal drug therapy based on a drug delivery system (DDS) for primary breast cancer. This DDS was designed to deliver miproxifen phosphate (TAT-59), an antiestrogen drug, to ductal lesions via the milk duct, where carcinomas originate, more efficiently than systemic administration, using an iontophoretic technique applied to the nipple (IP administration). Autoradiography imaging confirmed that TAT-59 was directly delivered to the milk duct using IP administration. The plasma concentrations of TAT-59 and its active metabolite DP-TAT-59 were quite low with IP administration. The area under the curve value of DP-TAT-59 in the mammary tissue was approximately 3 times higher with IP administration than with oral administration, at a 6-fold lower dose, indicating higher availability of the drug delivered via DDS than via systemic administration. The low plasma concentrations would limit adverse effects to minor ones. These characteristics show that this DDS is suitable for the delivery of active DP-TAT-59 to ductal lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Breast Neoplasms / drug therapy*
  • Dogs
  • Drug Delivery Systems*
  • Estrogen Antagonists / administration & dosage*
  • Estrogen Antagonists / pharmacokinetics
  • Female
  • Humans
  • Iontophoresis*
  • Mammary Glands, Animal / metabolism
  • Rats
  • Tamoxifen / administration & dosage
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacokinetics

Substances

  • Antineoplastic Agents
  • Estrogen Antagonists
  • Tamoxifen
  • TAT 59