Methods for quantitative determination of drug localized in the skin

Touítou, Elka; Meidan, Victor M.; Horwitz, Ehud

doi:10.1016/s0168-3659(98)00060-1

Cited by 137 publications

(54 citation statements)

References 37 publications

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“…Following exposure to CHG, the full-thickness human skin was sectioned to a depth of 1,500 m by sequential sectioning with a microtome, producing a total of 60 sections per skin sample. Skin sectioning has been used in many previous studies (21); however, the SC is often removed by tape stripping prior to sectioning of the skin. In this study, the full-thickness skin samples were sectioned throughout the sample without prior removal of the surface layers.…”

Section: Discussionmentioning

confidence: 99%

Penetration of Chlorhexidine into Human Skin

Kärpänen

Worthington

Conway

et al. 2008

Antimicrob Agents Chemother

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This study evaluated a model of skin permeation to determine the depth of delivery of chlorhexidine into full-thickness excised human skin following topical application of 2% (wt/vol) aqueous chlorhexidine digluconate. Skin permeation studies were performed on full-thickness human skin using Franz diffusion cells with exposure to chlorhexidine for 2 min, 30 min, and 24 h. The concentration of chlorhexidine extracted from skin sections was determined to a depth of 1,500 m following serial sectioning of the skin using a microtome and analysis by high-performance liquid chromatography. Poor penetration of chlorhexidine into skin following 2-min and 30-min exposures to chlorhexidine was observed (0.157 ؎ 0.047 and 0.077 ؎ 0.015 g/mg tissue within the top 100 m), and levels of chlorhexidine were minimal at deeper skin depths (less than 0.002 g/mg tissue below 300 m). After 24 h of exposure, there was more chlorhexidine within the upper 100-m sections (7.88 ؎ 1.37 g/mg tissue); however, the levels remained low (less than 1 g/mg tissue) at depths below 300 m. There was no detectable penetration through the full-thickness skin. The model presented in this study can be used to assess the permeation of antiseptic agents through various layers of skin in vitro. Aqueous chlorhexidine demonstrated poor permeation into the deeper layers of the skin, which may restrict the efficacy of skin antisepsis with this agent. This study lays the foundation for further research in adopting alternative strategies for enhanced skin antisepsis in clinical practice.Effective skin antisepsis is essential in preventing infections associated with invasive procedures, such as intravascular catheter insertion or surgery. A range of skin antiseptic agents are available in the clinical setting, such as povidone-iodine and chlorhexidine compounds at various concentrations with alcoholic or aqueous solutions. However, a 2% (wt/vol) chlorhexidine solution is the recommended agent to be used prior to invasive procedures according to the EPIC (evidence-based practice in infection control) and CDC guidelines (18,19). Two percent chlorhexidine digluconate (CHG) has been shown to significantly reduce intravascular catheter-related infections (14), yet 2% (wt/vol) CHG in 70% (vol/vol) isopropyl alcohol demonstrates activity superior to that of aqueous CHG solution in a preoperative skin preparation (9) and in vitro carrier tests (1). However, little is known about the kinetics of chlorhexidine skin permeation from either of these solutions (11,25). Microorganisms colonizing the skin not only reside on the skin surface but are also found to inhabit hair follicles and lower skin depths (8). Many antimicrobial agents exhibit restricted permeation of the skin (8) and fail to reach the deeper layers, including the hair follicles, which harbor coagulasenegative staphylococci (2,7,8,13,15) and propionibacteria (13). Commensal microorganisms may therefore persist at the site of incision following skin antisepsis (4, 22), and such resident organisms may cause infec...

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Section: Discussionmentioning

confidence: 99%

Penetration of Chlorhexidine into Human Skin

Kärpänen

Worthington

Conway

et al. 2008

Antimicrob Agents Chemother

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“…Consequently, several authors have studied the way to deliver greater amounts of this drug to the target site of virus infections, the basal epidermis, in order to increase the efficacy of the topical therapy. Therefore, the quantification of cidofovir within the skin and after the in vitro percutaneous penetration studies are essential for topical and transdermal research (Touitou et al, 1998).…”

Section: Cidofovir ((1-[(s)-3-hydroxy-2-(phosphonomethoxy)propyl] Cytmentioning

confidence: 99%

Optimization of topical cidofovir penetration using microparticles

Santoyo

Jalón

Ygartua

et al. 2002

International Journal of Pharmaceutics

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Cidofovir is a new class of antiviral agent with potent in vitro and in vivo activity against a broad spectrum of herpes viruses. The aim of this work was to obtain a prolonged therapeutic effect of cidofovir in the basal epidermis after its topical application. For this purpose, PLGA microparticles were prepared by solvent evaporation and spray-drying methods. Microparticles prepared by spray-drying showed a encapsulation efficiency of 80%.Conversely, for all the microspheres prepared by the W/O/W solvent evaporation method the encapsulation efficiency was low. Also, microparticles prepared by spray-drying showed a higher burst release. Skin penetration and distribution experiments were carried out with cidofovir-loaded microparticles prepared by spray-drying, since these carriers presented the best characteristics in terms of size and encapsulation efficiency. A cidofovir solution in 0.2% PVA served for comparison. Penetration experiments were carried out in Franz type diffusion cells with an available diffusion area of 1.76 cm 2 , using porcine skin. The results obtainedshowed that the amount of cidofovir penetrated, over a 24 h time period, was higher with the drug solution than with microparticles. Cidofovir distribution in porcine skin, after topical application of microparticles and drug solution for 24 h, was determined by horizontal slicing of the skin. The profiles obtained for the two formulations showed that the quantity of cidofovir retained in the skin decreased with the depth. Besides the amount of cidofovir found in the basal epidermis (120-150 μm) was much higher with microparticles than with the control solution. These data showed that cidofovir-loaded microparticles could improve cidofovir topical therapy since these vehicles increased drug retention in the basal epidermis and decreased its penetration through the skin.

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“…The examination periods were scheduled on the first and fourth days after skin treatment, respectively, and the regional skin was then cleaned to extract possible residual tamoxifen/phytonutrient particles by using distilled water followed by 50% ethanol. After euthanization and isolating the regional skin, an appropriate, sensitive analytical technique of HPLC (mentioned previously) was then employed to quantify the extracted drug [31,32]. Such a technique was also used to quantify the in vitro retention of tamoxifen/phytonutrient in the full thickness of each rat's skin.…”

Section: Determination Of Tamoxifen/phytonutrients Retention After Tomentioning

confidence: 99%