Skin penetration/permeation enhancers are compounds that improve (trans)dermal drug delivery. We designed hybrid terpene-amino acid enhancers by conjugating natural terpenes (citronellol, geraniol, nerol, farnesol, linalool, perillyl alcohol, menthol, borneol, carveol) or cinnamyl alcohol with 6-(dimethylamino)hexanoic acid through a biodegradable ester linker. The compounds were screened for their ability to increase the delivery of theophylline and hydrocortisone through and into human skin ex vivo. The citronellyl, bornyl and cinnamyl esters showed exceptional permeation-enhancing properties (enhancement ratios up to 82) while having low cellular toxicities. The barrier function of enhancer-treated skin (assessed by transepidermal water loss and electrical impedance) recovered within 24 h. Infrared spectroscopy suggested that these esters fluidized the stratum corneum lipids. Furthermore, the citronellyl ester increased the epidermal concentration of topically applied cidofovir, which is a potent antiviral and anticancer drug, by 15-fold. In conclusion, citronellyl 6-(dimethylamino)hexanoate is an outstanding enhancer with an advantageous combination of properties, which may improve the delivery of drugs that have a limited ability to cross biological barriers.
- MeSH
- alkoholy chemie farmakologie MeSH
- aplikace kožní MeSH
- buňky 3T3 MeSH
- chemie farmaceutická MeSH
- cidofovir aplikace a dávkování chemie farmakokinetika MeSH
- epidermis účinky léků metabolismus MeSH
- estery chemie farmakologie MeSH
- farmaceutické pomocné látky chemie farmakologie MeSH
- hydrokortison aplikace a dávkování chemie farmakokinetika MeSH
- keratinocyty MeSH
- lidé MeSH
- metabolismus lipidů účinky léků MeSH
- monoterpeny chemie MeSH
- myši MeSH
- permeabilita účinky léků MeSH
- perspiratio insensibilis účinky léků MeSH
- příprava léků metody MeSH
- terpeny chemie farmakologie MeSH
- testy akutní toxicity MeSH
- theofylin aplikace a dávkování chemie farmakokinetika MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Panthenol is an active substance used in dermatology to protect the health of the skin, to treat defects in the morphology of the stratum corneum. In cosmetology, hydrating, softening, and barrier function of panthenol are utilized. Detailed studies evaluating the efficacy of panthenol in cosmetic and pharmaceutical semisolid formulations and establishing its optimum concentration are needed. OBJECTIVES: To investigate whether an addition of 5-13 wt% panthenol in o/w and w/o emulsions increases hydration and supports the barrier properties of the skin. Rheological properties and sensory analysis of prepared formulations are supplemented. METHODS: Noninvasive instrumental methods in vivo were used. The hydration and barrier effect of semisolid formulations on the skin were observed for 48 hour; testing was conducted on 40 women. The effect was compared with formulations without any content of panthenol. The rheological and organoleptic properties of the formulations were evaluated. RESULTS: After applying either form of the formulations containing 7-11 wt% of panthenol hydration of the skin increased, transepidermal water loss decreased. pH of the skin shifted toward neutral after application of tested formulations. The rheological properties of the formulations were influenced by the type of vehicle, the amount of panthenol, and temperature. Sensory evaluation of both semisolid forms revealed statistically significant differences in o/w formulations with regard to spreadability. CONCLUSIONS: The presence of panthenol in an o/w and w/o semisolid formulations significantly enhances skin barrier repair and hydration of the stratum corneum. Better vehicle for the active substance as regards hydration proved o/w formulations.
- MeSH
- čití, cítění účinky léků MeSH
- dermatologické látky farmakologie MeSH
- dospělí MeSH
- emulze farmakologie MeSH
- epidermis účinky léků fyziologie MeSH
- fyziologie kůže účinky léků MeSH
- hydrofobní a hydrofilní interakce MeSH
- kosmetické přípravky farmakologie MeSH
- kyselina pantothenová analogy a deriváty farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- perspiratio insensibilis účinky léků MeSH
- příprava léků MeSH
- reologie MeSH
- voda metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Although keratin hydrolysates have become established as standard components in hair and nail cosmetics, studies on the moisturizing effects of keratin hydrolysates do not appear among contemporary literature. OBJECTIVES: To test if adding keratin hydrolysate into an ointment base increases hydration of the skin and improves skin barrier function, or diminishes trans-epidermal water loss. METHODS: Formulations were prepared containing 2%, 4%, and 6% keratin hydrolysates (based on weight of the ointment base). The moisturizing properties of keratin hydrolysates were tested by measuring skin hydration, trans-epidermal water loss and skin pH; measurements were carried out at intervals of 1, 2, 3, 4, 24, and 48 h. Testing was conducted on 10 women. RESULTS: As regards hydration, adding 2% keratin hydrolysate to the ointment base is optimal, as an increase of 14%-23% occurs in hydration of the stratum corneum. For trans-epidermal water loss, adding 4% KH to the ointment base is preferential, as this triggers a 26%-46% decrease in trans-epidermal water loss. CONCLUSIONS: Keratin hydrolysate acts as a humectant (it binds water from lower layers of the epidermis to the stratum corneum) as well as an occlusive (it reduces trans-epidermal water loss). The highly favorable properties of keratin hydrolysates are attributed to the wide distribution of keratin hydrolysates molecular weights; low-molecular weight fractions easily penetrate the SC, while high-molecular weight fractions form a protective film on the epidermis. Adding keratin hydrolysates to the ointment base did not cause phase separation even after 6 mo storage.
- MeSH
- dospělí MeSH
- epidermis chemie účinky léků fyziologie MeSH
- fyziologie kůže účinky léků MeSH
- hygroskopické látky farmakologie MeSH
- keratiny farmakologie MeSH
- koncentrace vodíkových iontů MeSH
- kosmetické přípravky farmakologie MeSH
- lidé MeSH
- masti MeSH
- perspiratio insensibilis účinky léků MeSH
- proteinové hydrolyzáty farmakologie MeSH
- voda metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: The work is aimed at the description and study of the hydration effect of different active substances (hyaluronic acid, sericin, glycerol, and urea) incorporated in two different vehicles commonly used for compounding pharmaceutical ingredients, gel, and emulsion. METHODS: The effects of the formulations were investigated by instrumental methods in vivo after their administration to the skin of volar forearms in a group of 20 healthy volunteers (women, mean age of 28 years). Hydration effect was observed by corneometry and barrier properties (TEWL) by tewametr at regular time intervals (1-26 h) after application of the prepared samples. RESULTS: The results indicate that the active substances incorporated in the emulsion moisturize the skin better compared to the same substances contained in the gel. Furthermore, it was found that these ingredients, whether they are present in the emulsion or in the gel, prevent TEWL in a similar manner. CONCLUSION: The study showed that differences exist among the tested active ingredients in their ability to moisturize the skin. These differences are dependent not only on the type and concentration of the active substance used but also on the type of vehicle in which they are applied. It was also found that the active substances influence the viscosity of the prepared formulations.
- MeSH
- dospělí MeSH
- emulze chemie MeSH
- farmaceutická vehikula chemie MeSH
- gely chemie MeSH
- kožní absorpce účinky léků fyziologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- perspiratio insensibilis účinky léků fyziologie MeSH
- pleťový krém aplikace a dávkování chemie MeSH
- příprava léků metody MeSH
- tělesná voda metabolismus MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
K porušení bariérové funkce kůže může dojít na podkladě vrozeném (atopická dermatitis, ichtyóza aj.) nebo získaném – (nežádoucím působením škodlivých látek a faktorů ze zevního prostředí). Porucha epidermální bariéry bývá spojená s poruchou vazby vody, což vede k vývoji stavu nadměrně suché kůže. Doba regenerace poškozené bariéry trvá 4–8 týdnů. Při porušené bariérové funkci se uplatňuje aplikace tzv. náhradních bariérových přípravků, upravujících urychleně nadměrnou ztrátu vody a chránící kožní povrch před nežádoucím působením látek ze zevního prostředí (moisturizéry, humektanty, emoliencia). Jako nový typ bariéroprotektivního přípravku je prezentován 2DERM krém (fa. ForLife Brno) spočívající na kombinaci mikronizovaného talku a oxidu zinečnatého v čistém lanolinu (MEDILAN) – na principu tzv. Pickeringových emulzí – ve kterých stabilizace mezifázového rozhraní O/V je zajištěna pevnými částečkami anorganické povahy – bez emulgátorů.
Contemporary and perspective possibilities of barrier disorder repair The function of epidermal barrier coud be damaged of the basis of congenital (atopic dermatitis, ichtyosis e. o.) or acquired cause (unwanted influence of various chemical substances and environmental factors). The disturbance of barrier function is connected with the develop of s. c. „dry skin state“ due to a waterbinding disturbance. Regeneration time is 4–8 weeks. An application of barrier protective cosmetic preparations (moisturizers, humectants, emollients) reduces the excessive waterloss and protects the skin surface against unwanted effects of some skin undesirable substances. As a new barrier protective preparate 2DERM cream (fa ForLife Brno) is presented-based on the combination of micronized talc and zincoxid with pure lanolin basis (MEDILAN) – on the basis of s. c. “Pickering emulsions type” – stabilisation of interphase boundary-line O/V by means of micronized anorganic particles– without emulgators.
- Klíčová slova
- bariérová funkce, hydratační mechanizmy pokožky, bariéroprotektivní přípravky, Pickeringovy emulze, 2DERM krém,
- MeSH
- aplikace lokální MeSH
- ceramidy terapeutické užití MeSH
- dermatologické látky terapeutické užití MeSH
- emoliencia farmakologie terapeutické užití MeSH
- epidermis patofyziologie MeSH
- kožní absorpce účinky léků MeSH
- kůže anatomie a histologie chemie patologie MeSH
- lanolin farmakologie terapeutické užití MeSH
- lidé MeSH
- péče o kůži metody MeSH
- perspiratio insensibilis účinky léků MeSH
- regenerace účinky léků MeSH
- zvlhčující látky farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Topical ceramide application is an effective therapeutic approach in skin disorders with disturbed barrier function, including atopic dermatitis and psoriasis. OBJECTIVES: To evaluate ceramide analogue N-tetracosanoyl-(l)-serine tetradecyl ester (14S24) using a novel ex vivo model. METHODS: Freshly excised human skin was disrupted by lipid extraction, tape stripping and sodium lauryl sulphate (SLS) treatment. Barrier perturbation was evaluated by the measurement of transepidermal water loss (TEWL), skin hydration and the penetration of model compound, theophylline (TH), assessed by microdialysis. The effect of topical 5% 14S24 was compared with a commercial formulation containing a skin lipid mixture (LR) and control formulation with no skin lipids (L). RESULTS: Both LR and 14S24 produced significant recovery of TEWL and TH penetration in extracted and tape-stripped skin with 14S24 being significantly more effective. In SLS-treated skin, 14S24 decreased TEWL but not TH penetration; LR was inactive. L improved skin hydration but not barrier characteristics. Weak correlation between TEWL and TH penetration was observed in extracted and tape-stripped skin but not in SLS-treated skin. CONCLUSIONS: Cutaneous microdialysis can serve as a useful tool for the evaluation of skin barrier recovery by topical formulations ex vivo whereas TEWL may not be an appropriate measure of skin barrier function in such studies. The excellent barrier repair activity of 14S24 could be beneficial in skin disorders with ceramide deficiency.
- MeSH
- ceramidy farmakologie MeSH
- detergenty MeSH
- dodecylsíran sodný MeSH
- dospělí MeSH
- financování organizované MeSH
- kožní absorpce účinky léků MeSH
- kůže metabolismus účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrodialýza metody MeSH
- perspiratio insensibilis účinky léků MeSH
- preklinické hodnocení léčiv metody MeSH
- rozpouštědla MeSH
- serin analogy a deriváty farmakologie MeSH
- techniky tkáňových kultur MeSH
- tělesná voda metabolismus MeSH
- theofylin farmakokinetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
