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PubMed2002

Inhibition of the microsomal metabolism of 1,8-cineole in the common brushtail possum (Trichosurus vulpecula) by terpenes and other chemicals.

1. Brushtail possums (Trichosurus vulpecula) ingest large amounts of terpenes in their diet of Eucalyptus leaf. Previously, we showed that dietary terpenes induce the cytochrome P450 enzymes (CYPs) responsible for their metabolism. The present study examined the effects of various CYP inhibitors on the metabolism of 1,8-cineole, the major dietary terpene, by liver microsomes from the possum and rat. 2. Ketoconazole inhibited the major reactions of terpene-induced microsomes in both species: 9-hydroxylation in the possum and 2-hydroxylation in the rat. This suggests the involvement of CYP3A enzymes, although in the possum there was a lack of the expected inhibition by troleandomycin or activation by alpha-naphthoflavone, highlighting the differences between species in CYP forms. Diethyldithiocarbamate also inhibited 9-hydroxylation in the possum, indicating that a CYP2E1-like enzyme contributes to this reaction. 3. Three other dietary terpenes were potent competitive inhibitors of 9-hydroxylation in the possum. K(i) ( micro M) (mean +/- SE, n = 4) were: alpha-pinene, 4.4 +/- 1.1; limonene, 7.8 +/- 2.1; p-cymene, 44.3 +/- 11.2; cuminyl alcohol (a p-cymene metabolite), 6.0 +/- 0.8. It appears likely that p-cymene acts via its metabolite to inhibit 1,8-cineole metabolism. 4. Inhibitory interactions between dietary terpenes, as well as other plant secondary compounds, may impose a significant constraint on foliage consumption in the common brushtail possum, therefore explaining the obligatory generalist nature of this browsing marsupial and other generalist herbivores.

Animals↗
PubMed2002

Microsomal metabolism and enzyme kinetics of the terpene p-cymene in the common brushtail possum (Trichosurus vulpecula), koala (Phascolarctos cinereus) and rat.

1. p-Cymene is an aromatic monoterpene found in the leaves of Eucalyptus spp. and is ingested in the diet of two marsupial folivores, the brushtail possum (Trichosurus vulpecula) and koala (Phascolarctos cinereus). The metabolism of p-cymene by liver microsomes from the possum, koala and rat (an animal whose diet is not terpene-rich) was examined. 2. The major p-cymene metabolite in each species was cuminyl alcohol, with smaller amounts of other side-chain alcohols being formed. No phenolic metabolites were detected. Possum and koala microsomes further oxidized cuminyl alcohol to cumic acid. 3. Pretreatment with a terpene diet more than doubled the V(max) for cuminyl alcohol formation by possum microsomes. This is similar to a previous finding by our group with 1,8-cineole and indicates that a terpene-containing diet results in induction of the enzymes responsible for terpene metabolism. 4. The rank order of the ability to metabolize p-cymene, measured by intrinsic clearance (Cl(int) = V(max)/K(m) [microl mg protein(-1) min(-1)]) was: terpene-treated possum (128)>control possum (107)>koala (69)>rat (38). 5. The findings support the hypothesis that animals that have adapted to a diet of Eucalypus leaf have a greater capacity than generalist feeders to metabolize dietary terpenes.

Adaptation, Physiological↗
PubMed2004

Indoor fine particles: the role of terpene emissions from consumer products.

Consumer products can emit significant quantities of terpenes, which can react with ozone (O3). Resulting byproducts include compounds with low vapor pressures that contribute to the growth of secondary organic aerosols (SOAs). The focus of this study was to evaluate the potential for SOA growth, in the presence of O3, following the use of a lime-scented liquid air freshener, a pine-scented solid air freshener, a lemon-scented general-purpose cleaner, a wood floor cleaner, and a perfume. Two chamber experiments were performed for each of these five terpene-containing agents, one at an elevated O3 concentration and-the other at a lower O3 concentration. Particle number and mass concentrations increased and O3 concentrations decreased during each experiment. Experiments with terpene-based air fresheners produced the highest increases in particle number and mass concentrations. The results of this study clearly demonstrate that homogeneous reactions between O3 and terpenes from various consumer products can lead to increases in fine particle mass concentrations when these products are used indoors. Particle increases can occur during periods of elevated outdoor O3 concentrations or indoor O3 generation, coupled with elevated terpene releases. Human exposure to fine particles can be reduced by minimizing indoor terpene concentrations or O3 concentrations.

Air Pollution, Indoor↗
PubMed2005

Selected oxidized fragrance terpenes are common contact allergens.

Terpenes are widely used fragrance compounds in fine fragrances, but also in domestic and occupational products. Terpenes oxidize easily due to autoxidation on air exposure. Previous studies have shown that limonene, linalool and caryophyllene are not allergenic themselves but readily form allergenic products on air-exposure. This study aimed to determine the frequency and characteristics of allergic reactions to selected oxidized fragrance terpenes other than limonene. In total 1511 consecutive dermatitis patients in 6 European dermatology centres were patch tested with oxidized fragrance terpenes and some oxidation fractions and compounds. Oxidized linalool and its hydroperoxide fraction were found to be common contact allergens. Of the patients tested, 1.3% showed a positive reaction to oxidized linalool and 1.1% to the hydroperoxide fraction. About 0.5% of the patients reacted to oxidized caryophyllene whereas 1 patient reacted to oxidized myrcene. Of the patients reacting to the oxidized terpenes, 58% had fragrance-related contact allergy and/or a positive history for adverse reaction to fragrances. Autoxidation of fragrance terpenes contributes greatly to fragrance allergy, which emphasizes the need of testing with compounds that patients are actually exposed to and not only with the ingredients originally applied in commercial formulations.

Allergens↗
PubMed1995

Terpene penetration enhancers in propylene glycol/water co-solvent systems: effectiveness and mechanism of action.

The effects of propylene glycol/water co-solvent systems and terpene penetration enhancers (1,8-cineole, menthone, (+)-limonene and nerolidol) on the absorption rate of the model hydrophilic permeant, 5-fluorouracil, were investigated using excised human skin. Similar fluxes for 5-fluorouracil were obtained from saturated enhancer-free co-solvent systems. Co-application of each terpene with the drug, both at saturation, in propylene glycol co-solvent systems increased drug flux significantly. Terpene activity depended on the propylene glycol content in the vehicles. Maximum fluxes were obtained from formulations containing the terpenes in 80% propylene glycol systems (highest concentration used), which when normalized to the flux from the pure vehicles yielded enhancement ratios of about 24, 21, 4 and 18, with 1,8-cineole, menthone, (+)-limonene and nerolidol, respectively. Combining the permeation studies with differential scanning calorimetry (DSC) and partitioning experiments revealed that increased lipid disruption is probably an important mechanism involved in the enhancing ability of formulations containing 1,8-cineole, menthone and nerolidol. This was clearly demonstrated by applying thermodynamic principles to interpret DSC results. This approach has indicated that these terpenes are probably able to disrupt stratum corneum lipids at physiological temperature as manifested by reductions in the entropy changes associated with the lipid-related transitions, particularly T2, the first major lipid transition. Additionally, increased drug partitioning contributed to the effect of the high propylene glycol content formulations. (+)-Limonene, as interpreted from DSC results, produced a freezing point-depression effect on stratum corneum lipids, suggesting little interaction with lipids at skin temperature; its small enhancement effect may involve phase separation of the oil in stratum corneum lipids. Terpenes in co-solvent systems such as propylene glycol/water at appropriate propylene glycol content might thus be useful vehicles for the delivery of drugs from topical formulations.

Antineoplastic Agents↗
PubMed2026

Therapeutic Potential of Terpenes in Lung Cancer: Modulation of 4-Oxo- Retinoic Acid, TNF-α, NF-κB, and HDAC2 Pathways.

Non-small cell lung cancer (NSCLC) includes various epithelial malignancies, such as squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Despite advancements in surgical resection, chemoradiotherapy, and multimodal therapies, NSCLC prognosis remains challenging due to its complex molecular landscape, drug resistance, and high treatment costs. Recent research highlights the potential of natural compounds, particularly terpenes and terpenoids, derived from essential oils (EOs), to enhance NSCLC treatment. These compounds exhibit anticancer properties and modulate key pathways like the 4-oxo-retinoic acid pathway, TNF-α signaling, NF-κB activation, and histone deacetylases (HDACs). Retinoids, a subclass of terpenes, show both chemopreventive and therapeutic benefits, especially when combined with other agents, though challenges in dosing and delivery methods limit their clinical application. Terpenes may also synergize with emerging therapies, such as antiangiogenic treatments and immunotherapy, to improve outcomes. Biomarkers, including genomic, epigenomic, and proteomic markers, play a critical role in predicting responses to terpene-based treatments, supporting personalized medicine. The integration of terpenes into existing regimens, in combination with conventional therapies, holds promise in overcoming clinical challenges, improving patient outcomes, and advancing natural compound use in modern oncology. Future research should focus on optimizing terpene therapies and addressing clinical hurdles.

Humans↗
PubMed2005

Lepidopteran herbivory and oral factors induce transcripts encoding novel terpene synthases in Medicago truncatula.

Terpenes are an important class of defense compounds that accumulate in plants after pathogen infection or arthropod injury. Sequences predicted to encode terpene synthases were selected from an expressed sequence tag (EST) database of Medicago truncatula. Four putative terpene synthase clones (MtTps1-MtTps4), originating from a chewing insect-damaged M. truncatula leaf cDNA library, were isolated. Transcript levels of each gene examined increased in response to artificial wounding, Spodoptera exigua herbivory, and treatment with volatile methyl jasmonate (meJA). Addition of S. exigua regurgitant to wound sites triggered transcript accumulation of MtTps1 and levels increased with higher concentrations of regurgitant. Furthermore, induction of MtTps1 occurred after application of N-linolenoyl-glutamate or N-linoleoyl-glutamate, factors found in lepidopteran regurgitant. Genomic DNA blots indicate that each of the putative proteins is encoded by a single-copy gene or a small gene family. Proteins encoded by MtTps3 and MtTps4 are imported into the soluble fraction of chloroplasts in in vitro assays, whereas proteins encoded by MtTps1 and MtTps2 are not imported into chloroplasts. Combined with sequence comparisons of multiple plant terpene synthases, the import data indicate that MtTps1 and MtTps2 likely encode sesquiterpene synthases and that MtTps3 and MtTps4 encode mono- or di-terpene synthases. In addition to serving as a valuable model legume species for genomic studies, M. truncatula should prove a valuable source of novel terpene-producing enzymes. Induction of wound-responsive genes by insect oral factors suggests that M. truncatula senses biotic damage through the presence of elicitors originating in the herbivore.

Alkyl and Aryl Transferases↗
PubMed2004

Transdermal delivery of zidovudine: effect of terpenes and their mechanism of action.

The effect of various oxygen-containing monoterpenes such as cineole, menthol, alpha-terpineol, menthone, pulegone and carvone was investigated on ex vivo permeation of zidovudine (AZT) across rat skin. Furthermore, saturation solubility of AZT, its stratum corneum (SC)/vehicle partition coefficient and activation energy for diffusion across skin with or without terpene(s) in vehicle (66.6% ethanol in water) were determined to understand their mechanism of action. All the terpenes studied significantly increased transdermal flux of AZT in comparison to vehicle (p<0.05) and their enhancement activities are in the following decreasing order: cineole>menthol>menthone approximately pulegone approximately alpha-terpineol>carvone>vehiclewater. On the other hand, saturation solubility and SC/vehicle partition coefficient of AZT were not significantly altered (p>0.05) by terpenes. Activation energies of AZT permeation across rat skin from water, vehicle and cineole in vehicle were measured to be 20.4, 18.6 and 10.6 kcal/mol, respectively. Interactions between terpenes and SC lipids were studied with molecular modeling and found that terpenes form hydrogen bonds (bond lengths<2 A) with lipid head groups. The mechanism of permeation enhancement of AZT by terpenes was explained with thermodynamic activity, SC/vehicle partition coefficient, activation energy and molecular modeling studies.

Adjuvants, Pharmaceutic↗
PubMed2002

The maize gene terpene synthase 1 encodes a sesquiterpene synthase catalyzing the formation of (E)-beta-farnesene, (E)-nerolidol, and (E,E)-farnesol after herbivore damage.

Maize (Zea mays) emits a mixture of volatile compounds upon attack by the Egyptian cotton leafworm (Spodoptera littoralis). These substances, primarily mono- and sesquiterpenes, are used by parasitic wasps to locate the lepidopteran larvae, which are their natural hosts. This interaction among plant, lepidopteran larvae, and hymenopteran parasitoids benefits the plant and has been termed indirect defense. The committed step in the biosynthesis of the different skeletal types of mono- and sesquiterpenes is catalyzed by terpene synthases, a class of enzymes that forms a large variety of mono- and sesquiterpene products from prenyl diphosphate precursors. We isolated a terpene synthase gene, terpene synthase 1 (tps1), from maize that exhibits only a low degree of sequence identity to previously identified terpene synthases. Upon expression in a bacterial system, the encoded enzyme produced the acyclic sesquiterpenes, (E)-beta-farnesene, (E,E)-farnesol, and (3R)-(E)-nerolidol, the last an intermediate in the formation of (3E)-4,8-dimethyl-1,3,7-nonatriene. Both (E)-beta-farnesene and (3E)-4,8-dimethyl-1,3,7-nonatriene are prominent compounds of the maize volatile blend that is emitted after herbivore damage. The biochemical characteristics of the encoded enzyme are similar to those of terpene synthases from both gymnosperms and dicotyledonous angiosperms, suggesting that catalysis involves a similar electrophilic reaction mechanism. The transcript level of tps1 in the maize cv B73 was elevated after herbivory, mechanical damage, and treatment with elicitors. In contrast, the increase in the transcript level of the tps1 gene or gene homolog in the maize cv Delprim after herbivory was less pronounced, suggesting that the regulation of terpene synthase expression may vary among maize varieties.

Alkyl and Aryl Transferases↗
PubMed2004

The variability of sesquiterpenes emitted from two Zea mays cultivars is controlled by allelic variation of two terpene synthase genes encoding stereoselective multiple product enzymes.

The mature leaves and husks of Zea mays release a complex blend of terpene volatiles after anthesis consisting predominantly of bisabolane-, sesquithujane-, and bergamotane-type sesquiterpenes. The varieties B73 and Delprim release the same volatile constituents but in significantly different proportions. To study the molecular genetic and biochemical mechanisms controlling terpene diversity and distribution in these varieties, we isolated the closely related terpene synthase genes terpene synthase4 (tps4) and tps5 from both varieties. The encoded enzymes, TPS4 and TPS5, each formed the same complex mixture of sesquiterpenes from the precursor farnesyl diphosphate but with different proportions of products. These mixtures correspond to the sesquiterpene blends observed in the varieties B73 and Delprim, respectively. The differences in the stereoselectivity of TPS4 and TPS5 are determined by four amino acid substitutions with the most important being a Gly instead of an Ala residue at position 409 at the catalytic site of the enzyme. Although both varieties contain tps4 and tps5 alleles, their differences in terpene composition result from the fact that B73 has only a single functional allele of tps4 and no functional alleles of tps5, whereas Delprim has only a functional allele of tps5 and no functional alleles of tps4. Lack of functionality was shown to be attributable to frame-shift mutations or amino acid substitutions that greatly reduce the activity of their encoded proteins. Therefore, the diversity of sesquiterpenes in these two maize cultivars is strongly influenced by single nucleotide changes in the alleles of two terpene synthase genes.

Alkyl and Aryl Transferases↗
PubMed2002

Terpenes in propylene glycol as skin-penetration enhancers: permeation and partition of haloperidol, Fourier transform infrared spectroscopy, and differential scanning calorimetry.

The respective alcoholic terpenes carvacrol, linalool, and alpha-terpineol were used at 5% w/v in propylene glycol (PG) to increase the in vitro permeation of haloperidol (HP) through human skin. The possible enhancement mechanism was then elucidated with HP-stratum corneum (SC) binding studies, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The greatest increase in the permeation of HP was achieved with linalool followed by carvacrol and terpineol. HP permeation with linalool was predicted to reach a therapeutic plasma concentration and therapeutic daily-permeated amounts. Carvacrol increased lag time, which was attributed to slow redistribution of the enhancer within SC. Carvacrol increased the partition of the drug to the pulverized SC. Pure PG extracted lipids from SC but less than that achieved by the terpenes in PG. Terpenes extracted lipids to a similar extent. An increase in bilayer cohesion in the remaining lipids present in the SC could be attributed to the alignment of terpenes within the lipid bilayer. The higher permeation with linalool was attributed to its molecular orientation within the lipid bilayer. Terpenes showed different rates of SC dehydration but did not change the percentages of secondary structures of keratin.

Calorimetry, Differential Scanning↗
PubMed2006

Effect of intraspecific competition and substrate type on terpene emissions from some Mediterranean plant species.

Competition is an important factor that has been extensively reported in the Mediterranean area. There is evidence that leaf terpene accumulation may vary between plants growing on calcareous and siliceous soils. In the present study, leaf terpene emissions from potted seedlings of Pinus halepensis, Cistus albidus, and Quercus coccifera, growing under natural environmental conditions on calcareous and siliceous substrates, were studied by using a bag enclosure method. In both substrates, seedlings were potted alone and in intraspecific competition, to examine the effect of substrate type and that of intraspecific competition on terpene emissions. The results showed that competition favored: (i) overall monoterpene and sesquiterpene emissions from Q. coccifera; (ii) overall monoterpene emissions from P. halepensis; (iii) overall sesquiterpene emissions from C. albidus. Substrate type affected terpene emissions to a limited extent and in a species-specific way. Whereas for Q. coccifera, the overall monoterpene emissions and that of Allo-aromadendrene were favored on siliceous substrate, no significant changes were found in emissions from P. halepensis. Only the release of AR-curcumene from C. albidus was higher on siliceous substrate. We also found high variability in terpene emission composition from the study species, particularly for P. halepensis and Q. coccifera. These two species released both monoterpenes and sesquiterpenes, instead of monoterpenes only, as shown in previous studies.

Analysis of Variance↗
PubMed1988

Effect of dietary terpenes on glucuronic acid excretion and ascorbic acid turnover in the brushtail possum (Trichosurus vulpecula).

1. Glucuronic acid was excreted in the urine of the brushtail possum, Trichosurus vulpecula, in response to dietary terpenes (essential oils found in Eucalyptus foliage). 2. The relationship between urinary glucuronic acid and the estimated terpene content of the diet was not equimolar, but varied from 1-17%, with levels of 5-39% found in animals maintained on terpenes or eucalypt leaves for several weeks. 3. Blood levels of ascorbate and the turnover rate of ascorbate were increased in the brushtail possum in response to dietary terpenes. 4. The presence of an active glucuronic acid pathway and associated glucose-ascorbate-glucose cycle was postulated for the brushtail possum and the other arboreal marsupials, Pseudocheirus peregrinus (common ringtail possum) and Petauroides volans (greater glider). 5. By means of these pathways these animals may utilise the high ascorbate content of Eucalyptus leaves to conserve glucose required for synthesis of glucuronic acid used for conjugation of dietary terpenes.

Animals↗
PubMed2003

Cutaneous absorption and elimination of three acyclic terpenes--in vitro studies.

The purpose of the study was to investigete skin absorption and elimination of three acyclic terpenes: citronellol (C), linalool (L) and linalyl acetate (LA). The pure terpenes were applied onto the human skin in vitro, and after 1-4 h, their content in the stratum corneum layers and in the epidermis/dermis was determined using gas chromatography. Similarly, the amounts of terpenes in the skin were analysed during 4 h following 1-h absorption. Good absorption to the all skin layers was demonstrated as soon as after 1 h: the total skin cumulation of L, LA and C was 827, 124 and 954 microg/cm2, respectively. A self-promoting absorption was observed for L, since the amount of this terpene analysed in the stratum corneum after 1 h was 78.3, rising to 479 microg/cm2 after 4 h. During the elimination phase, a constant drop in the total amount in the skin was observed only for C, while the total skin content of L and LA did not change, although diffusion from the stratum corneum to epidermis/dermis occurred. The log P values of the terpenes were calculated using three different programs, but generally, neither absorption nor elimination can be directly correlated with the physicochemical parameters, despite of the fact that the least absorption was observed for the most lipophilic LA.

Acyclic Monoterpenes↗
PubMed2002

Terpenes in ethanol: haloperidol permeation and partition through human skin and stratum corneum changes.

Carvacrol, linalool and alpha-terpineol (5% w/v) in 50% ethanol were used to enhance the permeation of haloperidol (HP) through human skin in vitro and their enhancement mechanism was investigated with HP-stratum corneum (SC) binding studies, fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Carvacrol followed by terpineol and linalool enhanced flux and permeability coefficient but only carvacrol provided the required plasma concentration and the permeated daily doses. All terpenes increased the activity coefficient of HP in the skin. Carvacrol increased the lag time, which could be due to slow redistribution within SC. The thermogram of hydrated SC showed two lipid endotherms T1 and T2 at 65 and 78 degrees C and protein endotherm T3 at 97 degrees C. All endotherms were absent after SC treated for 48 h with 12 ml of terpene solutions and a decrease in melting points (m.p.) of lipids with a shift of protein endotherm were observed after 12 h treatment with 7 ml of terpene solutions. Linalool and terpineol decreased the m.p. of T1 to 33 degrees C. Carvacrol increased the T1 peak area, which was attributed to lateral lipid bilayer swelling. The IR spectra showed decreases in peak areas and heights of CH2 stretchings but did not show shift of these peaks, increase in their peak widths and shift in amide bands. All the three terpenes disrupted the lipid bilayer and extracted the lipids. Moreover, carvacrol increased the partition of HP whilst linalool and terpineol fluidized the lipids at skin temperature. There could be other possible protein-terpene interactions.

Antipsychotic Agents↗
PubMed2001

The effects of terpene enhancers on the percutaneous permeation of drugs with different lipophilicities.

Four model drugs were selected based on their lipophilicity denoted as log P (nicardipine hydrochloride log P -0.99 +/- 0.1, hydrocortisone log P 1.43 +/- 0.47, carbamazepine log P 2.67 +/- 0.38, and tamoxifen log P 7.87 +/- 0.75). The enhancing activities of four terpene enhancers (fenchone log P 2.13 +/- 0.30, thymol log P 3.28 +/- 0.20, D-limonene log P 4.58 +/- 0.23, and nerolidol log P 5.36 +/- 0.38) were tested in vitro across full thickness hairless mouse skin with each of the evaluated drugs formulated in hydroxypropyl cellulose gel formulations. The relationships between lipophilicity (log P) of the terpene enhancers and model drugs and efficacy (represented by the enhancement ratio of flux ER(flux)) of the drugs when coadministered with the enhancers were examined using linear regression. Terpene enhancers had significant effect on the percutaneous permeation of the model drugs. Nerolidol (highest lipophilicity) provided the highest increase in the flux of the evaluated model drugs. The flux of nicardipine hydrochloride increased by approximately 135-fold, hydrocortisone by 33-fold, carbamazepine 8-fold, and tamoxifen 2-fold. The lowest increase in the flux was observed with fenchone. Linear relationships were generated between the ER(flux) of nicardipine hydrochloride, hydrocortisone, carbamazepine, and tamoxifen and the log P of the terpene enhancers [r = 0.951, (P = 0.049), r = 0.977, (P = 0.023), r = 0.942, (P = 0.057), and r = 0.874, (P = 0.126), respectively]. Furthermore, the four terpene enhancers produced linear relationships, indicating that they were more effective at enhancing the penetration of hydrophilic drugs rather than lipophilic drugs r=-0.824 (P=0.176) for fenchone, r = -0.891 (P = 0.109) for thymol, r = -0.846 (P = 0.154) for limonene, and r = -0.769 (P = 0.232) for nerolidol.

Cellulose↗
PubMed2001

In vitro studies on penetration of terpenes from matrix-type transdermal systems through human skin.

Polyurethane matrices containing up to 39% of the terpenes eucalyptol, L-limonene, D-limonene, dipentene or terpinolene were produced. Release of the terpenes directly to the acceptor fluid, as well as through isolated human epidermis and dermis, was studied. In the presence of dermis the penetration profiles were very similar to the release profiles, indicating that dermis does not present a barrier for penetration of terpenes. For all terpenes the penetration was slower in the presence of epidermis (K(p) was in the range 0.21-1.8x10(-3) cm/h). Release and penetration through the epidermis and dermis were fastest for dipenetene (mixture of D-limonene and L-limonene), being at least 3-4 times faster than for D-limonene and L-limonene. Large amounts of terpenes found in epidermis (approximately 1.5 mg/cm(2)) indicate that affinity of these compounds to the stratum corneum is very high.

Administration, Cutaneous↗
PubMed2001

Effect of passive and iontophoretic skin pretreatments with terpenes on the in vitro skin transport of piroxicam.

The enhancing effect of several terpenes (thymol, menthone and 1,8-cineole) in the percutaneous permeation of piroxicam (Px), either passive or iontophoretically, was investigated. These terpenes were applied, on the skin membrane, as a passive and iontophoretic skin pretreatment. Px was delivered from carbopol gels containing hydroxypropyl-beta-cyclodextrin (2% w/w Px). An increase in Px flux values, both passive and iontophoretic after skin pretreatment with 5% terpenes/50% EtOH, was found to be in the following order: thymol>menthone>1,8-cineole. Iontophoretic skin pretreatment with terpenes produced a slight increase in the passive flux of Px, in comparison with the passive skin pretreatment. This result indicated that iontophoresis could modify the skin morphology and consequently, increase the passive transport of Px. However, when Px was transported iontophoretically, passive skin pretreatment with terpenes, produced higher flux values than iontophoretic skin pretreatment. These results could be explained by the fact that with the iontophoretic pretreatment, terpenes could penetrate into the skin and limitate the movement of the ionized species, across the skin, during the iontophoretic experiments. The amount of Px retained in the skin after all experiments was related to flux values across skin.

Acrylic Resins↗