(+)-trans-Isolimonene

Sensitization potential and potency of terpene hydroperoxides in the COCAT method.[Pubmed:30963590]

Contact Dermatitis. 2019 Apr 8.

BACKGROUND: Positive patch tests to mixtures of oxidized terpenes containing allergenic hydroperoxides are frequently reported. However, human sensitization data for these hydroperoxides are not available. OBJECTIVES: To analyze and evaluate human sensitization potential and potency of hydroperoxides in vitro using human cells. MATERIALS/METHODS: Limonene-1-hydroperoxide, limonene-2-hydroperoxide, citronellol-7-hydroperoxide, cumene hydroperoxide, 1-(1-hydroperoxy-1-methylethyl)cyclohexene and mixtures of citronellol hydroperoxides (isomers at positions 6/7) and linalool hydroperoxides (isomers at positions 6/7) were studied. All compounds were synthesized except for cumene hydroperoxide that was commercially available. Their potential and potency to activate dendritic cells (DC) was evaluated by measuring the upregulation of CD86 and CD54 on THP-1 cells upon exposure in the cocultured activation test (COCAT) consisting of HaCaT (human keratinocyte cell line) and THP-1 monocytes (as surrogate for DC). RESULTS: Hydroperoxides upregulated CD86 and/or CD54 on cocultured THP-1 cells in a concentration-dependent manner. The results are comparable with their sensitization potency ranking in predictive animal models. CONCLUSIONS: For the first time, human sensitization potential and potency of several hydroperoxides were determined using human cells by the COCAT method. This article is protected by copyright. All rights reserved.

Cationic Moieties in Polystyrene Gels Swollen with d-Limonene Improved Transdermal Delivery System.[Pubmed:30961125]

Polymers (Basel). 2018 Oct 27;10(11). pii: polym10111200.

d-limonene, a terpene and natural compound, has been found to be an excellent penetration enhancer for transdermal drug delivery (TDD). It hence has been incorporated within various transdermal formulations. Herein, we report the application of polystyrene gel swollen with d-limonene and its derivatives for TDD. Poly(styrene-co-divinylbenzene) (PS gel), poly(styrene-co-divinylbenzene-co-4-vinylpyridine) (PS-4VP) gel and poly(styrene-co-divinylbenzene-co-(vinylbenzyl) trimethylammonium chloride) (PS-VBAC gel) were employed as chemical gels to improve the stability of the TDD substrates. The drug permeation properties from the PS gels swollen in limonene were examined, regarding the effect of its network density as well as their rheological properties. The lowest density of the network showed the highest steady flux of the permeation at 43.7 +/- 0.3 mug/cm(2). FT-IR spectra were confirmed for PS-4VP and PS-VBAC, bearing cationic moieties and they could control the release of ibuprofen by the electrostatic interaction at the interface of organogel and skin. The steady state flux of skin permeation got low values from 55.2 +/- 0.8 to 11.6 +/- 2.0 mug/cm(2), when the cationic moieties were increased. Moreover, the chemical network of PS gel swollen in limonene showed high mechanical stability illustrated by elastic modulus (G') of about 98 kPa for 10% cross-linked PS gel. The developed PS gels swollen in limonene show highly promising results, suggesting their possible application in TDD.

Self-microemulsifying Drug Delivery System for Improved Oral Delivery of Limonene: Preparation, Characterization, in vitro and in vivo Evaluation.[Pubmed:30915610]

AAPS PharmSciTech. 2019 Mar 26;20(4):153.

The current investigation aimed at formulating self-microemulsifying drug delivery system (SMEDDS) to ameliorate oral bioavailability of a hydrophobic functional ingredient, limonene. Solubility test, compatibility test, and pseudo-ternary phase diagrams (PTPD) were adopted to screen the optimal compositions of limonene-SMEDDS (L-SMEDDS). The characteristics of this system assessed in vitro, mainly included determination of particle size distribution, observation of morphology via transmission electron microscopy (TEM), testing of drug release in different dissolution media, and evaluation of stability. The oral bioavailability study in vivo of the formulated limonene was performed in rats with the free limonene as the reference. Compared with the free limonene, the distribution study of L-SMEDDS was conducted in Kunming mice after oral administration. The optimized SMEDDS (ethyl oleate, 14.2%; Cremophor EL, 28.6%; isopropanol, 28.6%; and loaded limonene, 28.6%) under the TEM (about 100 nm) was spherical with no significant variations in size/appearance for 30 days at 4, 25, and 60 degrees C. In comparison with free limonene, higher than 89.0% of limonene was released from SMEDDS within 10 min in different dissolution media. An in vivo study showed a 3.71-fold improved oral bioavailability of the formulated limonene compared to the free limonene. The tissue distribution results showed that limonene predominantly accumulated in the various tissues for the L-SMEDDS compared with the free limonene. Hence, L-SMEDDS could remarkably improve the concentration of limonene in the various organs. These findings hinted that the oral bioavailability of limonene could be improved via an effectual delivery system like SMEDDS.