Abstract
The aim of this work was to evaluate capability of site-specific delivery of a transdermal patch through determination of letrozole in local tissues disposition in female mice. After transdermal administration, the letrozole levels in skin, muscle, and plasma were 10.4–49.3 μg/g, 1.64–6.89 μg/g, and 0.35–1.64 μg/mL, respectively. However, after the mice received letrozole suspension, the drug concentration of plasma and muscle were 0.20–4.80 μg/mL and 0.15–2.38 μg/g. There was even no drug determined in skin through all experiments. Compared with oral administration, the transdermal patch for site-specific delivery of letrozole could produce high drug concentrations in skin and muscle and meanwhile obtain low drug level in plasma. These findings show that letrozole transdermal patch is an appropriate delivery system for application to the breast tumor region for site-specific drug delivery to obtain a high local drug concentration and low circulating drug concentrations avoiding the risk of systemic side effects.
This is a preview of subscription content, log in via an institution to check access.
References
Chen S, Masri S, Wang X, Phung S, Yuan YC, Wu XW. What do we know about the mechanisms of aromatase inhibitor resistance. J Steroid Biochem Mol Biol. 2006;102:232–40.
Jürgen G. Breast cancer tissue estrogens and their manipulation with aromatase inhibitors and inactivators. J Steroid Biochem Mol Biol. 2003;86:245–53.
VanLandeghem AAJ, Poortman J, Nabuurs M, Thijssen JHH. Endogenous concentration and subcellular distribution of estrogens in normal and malignant breast tissue. Cancer Res. 1985;45:2900–4.
Lønning PE, Dowsett M, Powles TJ. Postmenopausal estrogen synthesis and metabolism: alterations caused by aromatase inhibitors used for the treatment of breast cancer. J Steroid Biochem. 1990;35:355–66.
Chetrite GS, CortesPrieto J, Philippe JC, Wright F, Pasqualini JR. Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol. 2000;72:23–7.
Geisler J, Lønning PE. Endocrine effects of aromatase inhibitors and inactivators in vivo: review of data and method limitations. J Steroid Biochem Mole Biol. 2005;95:75–81.
Labrie F, Luu TV, Labrie C, Belanger A, Simard J, Lin SX. Endocrine and intracrine sources of androgens in women: inhibition of breast cancer and other roles of androgens and their precursor dehydroepiandrosterone. Endocr Rev. 2003;24:152–82.
Mom CH, Buijs C, Willemse PH, Mourits MJ, De Vries EG. Hot flushes in breast cancer patients. Crit Rev Oncol Hematol. 2006;57:63–77.
Edith AP. The balance between risks and benefits: long-term use of aromatase inhibitors. Eur J Cancer. 2006;Supp4:16–25.
Miki Y, Suzuki T, Sasano H. Aromatase inhibitor and bone. Biomed Pharmacother. 2007;61:540–2.
Tilson-Mallett N, Santner SJ, Feil PD, Santen RJ. Biological significance of aromatase activity in human breast tumors. J Clin Endocrinol Metab. 1983;57:1125–8.
Brodie A, Long B, Lu Q. Aromatase expression in the human breast. Breast Cancer Res Treat. 1998;49 Suppl 1:S85–91.
Bulun SE, Chen D, Lu M, Zhao H, Cheng Y, Demura M, et al. Aromatase excess in cancers of breast, endometrium and ovary. J Steroid Biochem Mol Biol. 2007;106:81–96.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, L., Xu, X., Fang, L. et al. The Transdermal Patches for Site-Specific Delivery of Letrozole: A New Option for Breast Cancer Therapy. AAPS PharmSciTech 11, 1054–1057 (2010). https://doi.org/10.1208/s12249-010-9465-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-010-9465-1