Evaluation of skin absorption of drugs from topical and transdermal formulations

ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed

Interaction of surfactants (edge activators) and skin penetration enhancers with liposomes.

NoIncorporating edge activators (surfactants) into liposomes was shown previously to improve estradiol vesicular skin delivery; this phenomenon was concentration dependent with low or high concentrations being less effective. Replacing surfactants with limonene produced similar behaviour, but oleic acid effects were linear with concentration up to 16% (w/w), beyond which it was incompatible with the phospholipid. This present study thus employed high sensitivity differential scanning calorimetry to probe interactions of additives with dipalmitoylphosphatidylcholine (DPPC) membranes to explain such results. Cholesterol was included as an example of a membrane stabiliser that removed the DPPC pre-transition and produced vesicles with a higher transition temperature (Tm). Surfactants also removed the lipid pre-transition but reduced Tm and co-operativity of the main peak. At higher concentrations, surfactants also formed new species, possibly mixed micelles with a lower Tm. The formation of mixed micelles may explain reduced skin delivery from liposomes containing high concentrations of surfactants. Limonene did not remove the pre-transition but reduced Tm and co-operativity of the main peak, apparently forming new species at high concentrations, again correlating with vesicular delivery of estradiol. Oleic acid obliterated the pre-transition. The Tm and the co-operativity of the main peak were reduced with oleic acid concentrations up to 33.2 mol%, above which there was no further change. At higher concentrations, phase separation was evident, confirming previous skin transport findings

An update on C-reactive protein for intensivists.

This review aims to summarise the physiology of C-reactive protein (CRP), its possible roles and limitations as an inflammatory and infective marker in intensive care medicine, and also the emerging roles of CRP in the pathogenesis of cardiovascular and autoimmune diseases. Observational and animal studies on uses of CRP were retrieved from the PubMed database without any language restrictions. Quantitative data were not pooled because of the heterogeneity of patient characteristics and disparate ways in which CRP was studied. Serum CRP concentrations are determined by the synthetic rate of its production in the liver regulated predominantly by interleukin-6. It has a half-life of 19 hours and is relatively slow in its onset and offset in response to an acute inflammatory process when compared to procalcitonin. It has some favourable properties and limitations as an inflammatory marker. An elevated CRP concentration is not specific to infections and the absolute CRP concentrations cannot be used to differentiate between bacterial, fungal and severe viral infections. The dynamic response of CRP to therapy that aims to modify the underlying inflammatory process and the clinical context of a patient are of pivotal importance when CRP concentrations are interpreted. CRP is found to be a significant partaker and prognostic factor in a wide range of cardiovascular and chronic diseases. In summary, CRP concentration is an important prognostic factor of many acute and chronic diseases. Serial CRP measurements may be useful to reflect a patient's response to therapy that aims to modify the underlying inflammatory process

Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety

Many modern cosmetic or sunscreen products contain nano-sized components. Nanoemulsions are transparent and have unique tactile and texture properties; nanocapsule, nanosome, noisome, or liposome formulations contain small vesicles (range: 50 to 5000 nm) consisting of traditional cosmetic materials that protect light- or oxygen-sensitive cosmetic ingredients. Transdermal delivery and cosmetic research suggests that vesicle materials may penetrate the stratum corneum (SC) of the human skin, but not into living skin. Depending on the physical/chemical properties of the ingredient and the formulation, nano-sized formulations may enhance or reduce skin penetration, albeit at a limited rate. Modern sunscreens contain insoluble titanium dioxide (TiO2) or zinc oxide (ZnO) nanoparticles (NP), which are colorless and reflect/scatter ultraviolet (UV) more efficiently than larger particles. Most available theoretical and experimental evidence suggests that insoluble NP do not penetrate into or through normal as well as compromised human skin. Oral and topical toxicity data suggest that TiO2 and ZnO NP have low systemic toxicity and are well tolerated on the skin. In vitro cytotoxicity, genotoxicity, and photogenotoxicity studies on TiO2 or other insoluble NP reporting uptake by cells, oxidative cell damage, or genotoxicity should be interpreted with caution, since such toxicities may be secondary to phagocytosis of mammalian cells exposed to high concentrations of insoluble particles. Caution needs to be exercised concerning topical exposure to other NP that either have characteristics enabling some skin penetration and/or have inherently toxic constituents. Studies on wear debris particles from surgical implants and other toxicity studies on insoluble particles support the traditional toxicology view that the hazard of small particles is mainly defined by the intrinsic toxicity of particles, as distinct from their particle size. There is little evidence supporting the principle that smaller particles have greater effects on the skin or other tissues or produce novel toxicities relative to micro-sized materials. Overall, the current weight of evidence suggests that nano-materials such as nano-sized vesicles or TiO2 and ZnO nanoparticles currently used in cosmetic preparations or sunscreens pose no risk to human skin or human health, although other NP may have properties that warrant safety evaluation on a case-by-case basis before human use