Novel iontophoretic administration method for local therapy of breast cancer.

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.

• Authors: Masahito Komuro, Kenichi Suzuki, Makoto Kanebako, Takashi Kawahara, Takeshige Otoi, Kenji Kitazato, Toshio Inagi, Kimiko Makino, Masakazu Toi, Hiroshi Terada
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 168 Issue 3 Pg. 298-306 (Jun 28 2013) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 23562634 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Estrogen Antagonists
• Tamoxifen
• TAT 59

Topics

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