The Transdermal Patches for Site-Specific Delivery of Letrozole: A New Option for Breast Cancer Therapy

Abstract

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.

Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy

“…This low inhibition is probably due to high drug lipophilicity, a reason for low bioavailability of oral posaconazole, and enhancement of drug bioavailability to up to 47% by high-fat food (Lipp, 2010). Drug lipophilicity and low apparent K d values for CYP27A1 (Table 1) make, however, ravuconazole and especially posaconazole, an approved Food and Drug Administration drug, good candidates for breast-specific drug delivery via transdermal patches, a route of administration that is currently under investigation (Li et al, 2010;Xi et al, 2010). Alternatively, posaconazole could be administered orally in combination with other antibreast cancer medications.…”

“…The mammary gland is a particularly suitable organ for tissue-specific drug delivery with efforts currently underway to administer some of the anticancer medication through the skin via transdermal patches (Li et al, 2010;Xi et al, 2010). This advantage of the mammary gland and body's tolerability to a partial lack of CYP27A1 activity supports enzyme potential as a pharmacologic target.…”

Transdermal and Oral dl-Methylphenidate–Ethanol Interactions in C57BL/6J Mice: Transesterification to Ethylphenidate and Elevation of d-Methylphenidate Concentrations

“…73 Although the present investigation appears to represent the first MTS study to use mice, previous preclinical studies have shown that shaved mice serve to model transdermal drug delivery. 74 Hairless or nude mice are more typically used for transdermal delivery studies across the range of patch technologies 75 ; however, the neuropharmacological reference strain status of the C57 mouse provided the justification for its use in investigating dl-MPH-ethanol interactions (see Introduction section). Maintaining the mice in the metabolic chambers for a total of 3 h allowed for the collection of adequate urine volume for analysis, while still permitting quantification of analytes from blood and brain.…”

Conserved early expression patterns of micromere specification genes in two echinoid species belonging to the orders clypeasteroida and echinoida

“…Although the present investigation appears to represent the first MTS study to use mice, previous preclinical studies have shown that shaved mice serve to model transdermal drug delivery 74. Hairless or nude mice are more typically used for transdermal delivery studies across the range of patch technologies75; however, the neuropharmacological reference strain status of the C57 mouse provided the justification for its use in investigating dl‐ MPH–ethanol interactions (see Introduction section).…”