Dermal delivery Dotaz Zobrazit nápovědu
The objective of this work was to investigate feasibility of transdermal and dermal delivery of adefovir (9-(2-phosphonomethoxyethyl)adenine), a broad-spectrum antiviral from the class of acyclic nucleoside phosphonates. Transport of 2% adefovir through and into porcine skin and effects of various solvents, pH, and permeation enhancers were studied in vitro using Franz diffusion cell. From aqueous donor samples, adefovir flux through the skin was 0.2-5.4 microg/cm2/h with greatest permeation rate at pH 7.8. The corresponding adefovir skin concentrations reached values of 120-350 microg/g of tissue. Increased solvent lipophilicity resulted in higher skin concentration but had only minor effect on adefovir flux. A significant influence of counter ions on both transdermal and dermal transport of adefovir zwitterion was observed at pH 3.4. Permeation enhancer dodecanol was ineffective, 1-dodecylazepan-2-one (Azone) and dodecyl 2-(dimethylamino)propionate (DDAIP) showed moderate activity. The highest adefovir flux (11.3+/-3.6 microg/cm2/h) and skin concentration (1549+/-416 microg/g) were achieved with 1% Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium 5-(dodecyloxycarbonyl)pentylcarbamate) at pH 4. This study suggests that, despite its hydrophilic and ionizable nature, adefovir can be successfully delivered through the skin.
- MeSH
- adenin analogy a deriváty aplikace a dávkování farmakokinetika MeSH
- antivirové látky aplikace a dávkování farmakokinetika MeSH
- aplikace kožní MeSH
- financování organizované MeSH
- koncentrace vodíkových iontů MeSH
- kožní absorpce účinky léků MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- organofosfonáty aplikace a dávkování farmakokinetika MeSH
- permeabilita MeSH
- pomocné látky MeSH
- rozpouštědla MeSH
- techniky in vitro MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- MeSH
- aplikace kožní MeSH
- kožní absorpce MeSH
- lékové formy MeSH
- Publikační typ
- přehledy MeSH
Hyaluronic acid (HA) hydrogels are interesting delivery systems for topical applications. Besides moisturizing the skin and improving wound healing, HA facilitates topical drug absorption and is highly compatible with labile biomacromolecules. Hence, in this study we investigated the influence of HA hydrogels with different molecular weights (5 kDa, 100 kDa, 1 MDa) on the skin absorption of the model protein bovine serum albumin (BSA) using fluorescence lifetime imaging microscopy (FLIM). To elucidate the interactions of HA with the stratum corneum and the skin absorption of HA itself, we combined FLIM and Fourier-transform infrared (FTIR) spectroscopy. Our results revealed distinct formulation and skin-dependent effects. In barrier deficient (tape-stripped) skin, BSA alone penetrated into dermal layers. When BSA and HA were applied together, however, penetration was restricted to the epidermis. In normal skin, penetration enhancement of BSA into the epidermis was observed when applying low molecular weight HA (5 kDa). Fluorescence resonance energy transfer analysis indicated close interactions between HA and BSA under these conditions. FTIR spectroscopic analysis of HA interactions with stratum corneum constituents showed an α-helix to β-sheet interconversion of keratin in the stratum corneum, increased skin hydration, and intense interactions between 100 kDa HA and the skin lipids resulting in a more disordered arrangement of the latter. In conclusion, HA hydrogels restricted the delivery of biomacromolecules to the stratum corneum and viable epidermis in barrier deficient skin, and therefore seem to be potential topical drug vehicles. In contrast, HA acted as an enhancer for delivery in normal skin, probably mediated by a combination of cotransport, increased skin hydration, and modifications of the stratum corneum properties.
- MeSH
- aplikace kožní MeSH
- kožní absorpce MeSH
- kůže metabolismus MeSH
- kyselina hyaluronová chemie MeSH
- prasata MeSH
- sérový albumin hovězí chemie metabolismus MeSH
- skot MeSH
- spektroskopie infračervená s Fourierovou transformací MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- durogesic, transtec,
- MeSH
- aplikace kožní MeSH
- buprenorfin aplikace a dávkování farmakologie škodlivé účinky MeSH
- fentanyl aplikace a dávkování farmakologie škodlivé účinky MeSH
- lékové transportní systémy metody MeSH
- narkotika aplikace a dávkování farmakologie MeSH
- nezvladatelná bolest farmakoterapie MeSH
- Publikační typ
- přehledy MeSH
Neurology, ISSN 0028-3878 Vol. 65, no. 2, suppl. 1, July 26, 2005
14 s. : il., tab. ; 28 cm
- MeSH
- agonisté dopaminu terapeutické užití MeSH
- aplikace kožní MeSH
- onemocnění motorického neuronu farmakoterapie MeSH
- Parkinsonova nemoc farmakoterapie MeSH
- Publikační typ
- sborníky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- neurologie
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Silymarin is a well-known standardized extract from the seeds of milk thistle (Silybum marianum L., Asteraceae) with a pleiotropic effect on human health, including skin anticancer potential. Detailed characterization of flavonolignans properties affecting interactions with human skin was of interest. The partition coefficients log Pow of main constitutive flavonolignans, taxifolin and their respective dehydro derivatives were determined by a High Performance Liquid Chromatography (HPLC) method and by mathematical (in silico) approaches in n-octanol/water and model lipid membranes. These parameters were compared with human skin intake ex vivo. The experimental log Pow values for individual diastereomers were estimated for the first time. The replacement of n-octanol with model lipid membranes in the theoretical lipophilicity estimation improved the prediction strength. During transdermal transport, all the studied compounds permeated the human skin ex vivo; none of them reached the acceptor liquid. Both experimental/theoretical tools allowed the studied polyphenols to be divided into two groups: low (taxifolin, silychristin, silydianin) vs. high (silybin, dehydrosilybin, isosilybin) lipophilicity and skin intake. In silico predictions can be usefully applied for estimating general lipophilicity trends, such as skin penetration or accumulation predictions. However, the theoretical models cannot yet provide the dermal delivery differences of compounds with very similar physico-chemical properties; e.g., between diastereomers.
- Publikační typ
- abstrakt z konference MeSH
Every year many drug molecules discovered to be effective in treatment of many diseases, however not all of these drugs succeed in reaching the market. One of the main reasons for such failure is the lipophilicity or low water solubility of these chemicals which results in poor bioavailability. Nanoemulsion has the ability to deliver these drugs in an efficient way. Nanoemulsion, which is usually o/w emulsion can incorporate this lipophilic drug into nanolipoidal droplets. However, the difficulty in applying liquid dosage form can be overcome by using nanoemulgel system. Nanoemulgel considered as a suitable way to deliver lipophilic drugs through topical route. This review tries to highlight the importance of nanoemulgel as a drug delivery system. The components of the systems have been explored and the methods of preparations including high energy methods and low energy methods have been discussed. Different methods were used in characterization of such delivery system; all of these methods and techniques were reviewed briefly. Finally, the recent researches about different applications of emulgel in local delivery or systemic delivery has been discussed. To conclude, the nanoemulgel applications in drug delivery is very promising and many products will find their way to the markets soon.
