Investigation of drug partition property in artificial sebum

Valiveti, Satyanarayana; Wesley, James A.; Lu, Guang Wei

doi:10.1016/j.ijpharm.2007.06.001

Cited by 33 publications

(14 citation statements)

References 13 publications

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“…(). To account for the uncertainty in partition coefficients and the possibility that K ssl_g may deviate somewhat from K oa (Valiveti et al., ), we assigned the low (0.3333 times nominal value) and high (three times nominal value) values used in the sensitivity analysis for K ssl_g and K sc_g such that each spans approximately 1 order of magnitude.…”

Section: Methodsmentioning

confidence: 99%

Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects

2016

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To better understand the dermal exposure pathway, we enhance an existing mechanistic model of transdermal uptake by including skin surface lipids (SSL) and consider the impact of clothing. Addition of SSL increases the overall resistance to uptake of SVOCs from air but also allows for rapid transfer of SVOCs to sinks like clothing or clean air. We test the model by simulating di-ethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) exposures of six bare-skinned (Weschler et al. 2015, Environ. Health Perspect., 123, 928) and one clothed participant (Morrison et al. 2016, J. Expo. Sci. Environ. Epidemiol., 26, 113). The model predicts total uptake values that are consistent with the measured values. For bare-skinned participants, the model predicts a normalized mass uptake of DEP of 3.1 (μg/m )/(μg/m ), whereas the experimental results range from 1.0 to 4.3 (μg/m )/(μg/m ); uptake of DnBP is somewhat overpredicted: 4.6 (μg/m )/(μg/m ) vs. the experimental range of 0.5-3.2 (μg/m )/(μg/m ). For the clothed participant, the model predicts higher than observed uptake for both species. Uncertainty in model inputs, including convective mass transfer coefficients, partition coefficients, and diffusion coefficients, could account for overpredictions. Simulations that include transfer of skin oil to clothing improve model predictions. A dynamic model that includes SSL is more sensitive to changes that impact external mass transfer such as putting on and removing clothes and bathing.

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Section: Methodsmentioning

confidence: 99%

Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects

2016

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“…Frequencies of CH 2 asymmetric and symmetric stretching bands in the ATR-FTIR spectra on the forearm and forehead by sebum treatments (n = 8). [20,21] using artificial sebum, which suggested that there is no correlation between log K sebum versus log K SC for compounds with different chemical structures, and maximal flux observed through sebum was found to be higher than the corresponding skin fluxes for a homologous series of 4-hydroxybenzoic acid esters.…”

Section: Effect Of Sebum Removal and Supplementation On Sebum Contentmentioning

confidence: 99%

Effects of Sebum on Drug Transport across the Human Stratum Corneum in vivo

Tsai¹,

Lu²,

Lin

et al. 2012

Skin Pharmacol Physiol

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The objective of this study was to investigate the effect of sebum on drug transport across the human stratum corneum (SC) in vivo for two model compounds, 4-cyanophenol (CP) and cimetidine (CM), of different lipophilicity and molecular size by utilizing noninvasive tape-stripping techniques, in conjunction with an unsteady-state diffusion model for data analysis. The results demonstrated that the SC permeability of the relatively hydrophilic CM on the forehead may be as much as four times the permeability on the forearm. The administration of sebum supplementation to the forearm increased the SC permeability of CM more than threefold, but did not have the same effect with regard to CP. Removal of sebum from the forehead demonstrated a small but significant effect (-22%) on the SC permeability of CM. The presence of sebum on the forehead or forearm increased the diffusion of both molecules, but the effect on partition varied between sites and drugs. The change in the SC permeability of the relatively hydrophilic drug using sebum treatment may be attributable to the altered barrier function of the SC due to the disordering structures of the intercellular lipid molecules.

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“…Although aerotolerant, P. acnes typically grows in the anaerobic environment of the infrainfundibulum of the pilosebaceous unit, where it releases lipases and digests local accumulations of the skin and sebum (oily substance produced by sebaceous glands). Sebum is primarily composed of glycerides, triglycerides, wax esters, squalene, and free fatty acids (40,61,62).…”

mentioning

confidence: 99%

In Vitro Antibacterial Activity of NB-003 against Propionibacterium acnes

Pannu

McCarthy

Martin

et al. 2011

Antimicrob Agents Chemother

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NB-003 and NB-003 gel formulations are oil-in-water nanoemulsions designed for use in bacterial infections. In vitro susceptibility of Propionibacterium acnes to NB-003 formulations and comparator drugs was evaluated. Both NB-003 formulations were bactericidal against all P. acnes isolates, including those that were erythromycin, clindamycin, and/or tetracycline resistant. In the absence of sebum, the MIC 90 s/minimum bactericidal concentrations (MBC 90 s) for NB-003, NB-003 gel, salicylic acid (SA), and benzoyl peroxide (BPO) were 0.5/2.0, 1.0/2.0, 1,000/2,000, and 50/200 g/ml, respectively. In the presence of 50% sebum, the MIC 90 s/MBC 90 s of NB003 and BPOs increased to 128/1,024 and 400/1,600 g/ml, respectively. The MIC 90 s/MBC 90 s of SA were not significantly impacted by the presence of sebum. A reduction in the MBC 90 s for NB-003 and BPO was observed when 2% SA or 0.5% BPO was integrated into the formulation, resulting in MIC 90 s/MBC 90 s of 128/256 g/ml for NB003 and 214/428 g/ml for BPO. The addition of EDTA enhanced the in vitro efficacy of 0.5% NB-003 in the presence or absence of 25% sebum. The addition of 5 mM EDTA to each well of the microtiter plate resulted in a >16-and >256-fold decrease in MIC 90 and MBC 90 , yielding a more potent MIC 90 /MBC 90 of <1/<1 g/ml. The kinetics of bactericidal activity of NB-003 against P. acnes were compared to those of a commercially available product of BPO. Electron micrographs of P. acnes treated with NB-003 showed complete disruption of bacteria. Assessment of spontaneous resistance of P. acnes revealed no stably resistant mutant strains.

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Investigation of drug partition property in artificial sebum

Cited by 33 publications

References 13 publications

Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects

Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects

Effects of Sebum on Drug Transport across the Human Stratum Corneum in vivo

In Vitro Antibacterial Activity of NB-003 against Propionibacterium acnes

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