Development of a Tape-Stripping Liquid Chromatography-Mass Spectrometry Method for Evaluating Skin Deposition of Topical Tazarotene
October 2021 | Volume 20 | Issue 10 | Original Article | 1105 | Copyright © October 2021
Published online September 21, 2021
Zoe D. Draelos MD, Matthew M. Draelos PhD
Dermatology Consulting Services, PLLC, High Point, NC
Standard in vitro and ex vivo techniques for evaluating topical drug penetration utilize skin that is physiologically unlike living skin and cannot assess intra-dermal drug deposition. We combined tape stripping with liquid chromatography-heated electrospray ionization-mass spectrometry (LC-ESI-MS) to assess in vivo deposition of tazarotene after application of 0.1% cream and 0.045% lotion formulations. Methods:
Ten healthy adult female participants had ~0.1 g of tazarotene lotion and cream applied to two sites each on opposite forearms. After 3 and 6 hours, 21 tape strips were used to sample progressively deeper skin layers. LC-ESI-MS was used to determine percent recovery of the applied tazarotene dose and the concentration of tazarotene recovered from even-numbered tape strips. Results:
At both sampling times, percent recovery was slightly higher with tazarotene 0.045% lotion versus 0.1% cream, though tazarotene concentrations were approximately 2-fold higher for cream than lotion at both superficial and deep skin layers. Absolute differences in tazarotene concentrations between 0.1% cream and 0.045% lotion decreased in progressively deeper skin layers, from 0.8 μg/mL at tape strip 2 to 0.09 μg/mL at tape strip 20 (6 hours post-application). Conclusions:
Tape stripping plus LC-ESI-MS—a consistent, accurate, and non-invasive method for assessing drug delivery into layers of living skin—can be used to assess in vivo deposition of topical formulations. Results from this study, when combined with clinical data, suggest that small tazarotene-deposition differences between lotion and cream in deeper skin layers are not clinically relevant; however, lower-dose 0.045% lotion may minimize tazarotene skin exposure versus 0.1% cream, potentially resulting in a more favorable tolerability profile. J Drugs Dermatol.
Topical medications for acne and other dermatological conditions are designed to penetrate skin layers and reach their target sites in a biologically active form at sufficient concentrations to elicit clinical effects. Improving drug delivery to an intended site is critical for increasing clinical effectiveness and decreasing side effects.1 A drug’s vehicle significantly impacts skin penetration and subsequent delivery of active ingredients2; thus, several methods have been developed to assess permeation properties of topical drugs to both evaluate and optimize novel drug formulations.3
Current standards for assessing topical drug penetration utilize in vitro and ex vivo techniques, including diffusion cell assays, but these techniques have limited clinical translatability. In a traditional diffusion cell assay, such as the Franz cell, drug is applied to explanted skin stretched over a collection chamber, and drug that passes through the skin into the collection chamber is sampled for analysis.3 Although this technique is useful, it has several inherent limitations. First, diffusion cell assays poorly reproduce complex biological systems, as excised skin is nonviable and does not possess active blood flow or functional enzymes.4 Second, only the drug that passes through the skin is collected; such transdermal delivery precludes the ability to measure drug within distinct compartments of the skin itself.1 In living skin, drug that passes completely through epidermis and dermis is quickly removed from the skin by the abundant dermal vasculature, and has systemic rather than dermal effects.5 Because the target for topical dermatologics is in the skin itself, drug passing into systemic circulation becomes clinically useless. Thus, given that skin is enzymatically active, and deposition can occur at different positions within the epidermis and dermis, new methods that allow for in vivo assessment of drug deposition within the skin are necessary to effectively evaluate topical drug formulations.
Tape stripping is a relatively non-invasive and well-tolerated method for the serial collection of tissue samples from progressively deeper skin layers.6 Since its early use as a tool for investigating stratum corneum anatomy and barrier function,6 improvements in analytical techniques have