Localization of human hair structural lipids using nanoscale infrared spectroscopy and imaging.

Atomic force microscopy (AFM) and infrared (IR) spectroscopy have been combined in a single instrument (AFM-IR) capable of producing IR spectra and absorption images at a sub-micrometer spatial resolution. This new device enables human hair to be spectroscopically characterized at levels not previously possible. In particular, it was possible to determine the location of structural lipids in the cuticle and cortex of hair. Samples of human hair were embedded, cross-sectioned, and mounted on ZnSe prisms. A tunable IR laser generating pulses of the order of 10 ns was used to excite sample films. Short duration thermomechanical waves, due to infrared absorption and resulting thermal expansion, were studied by monitoring the resulting excitation of the contact resonance modes of the AFM cantilever. Differences are observed in the IR absorbance intensity of long-chain methylene-containing functional groups between the outer cuticle, middle cortex, and inner medulla of the hair. An accumulation of structural lipids is clearly observed at the individual cuticle layer boundaries. This method should prove useful in the future for understanding the penetration mechanism of substances into hair as well as elucidating the chemical nature of alteration or possible damage according to depth and hair morphology.

Selective hair therapy: bringing science to the fiction.

Investigations on carrier-based drug delivery systems for higher selectivity in hair therapy have clearly evolved from dye release and model studies to highly sophisticated approaches, many of which specifically tackle hair indications and the delivery of hair-relevant molecules. Here, we group recent hair disease-oriented work into efforts towards (i) improved delivery of conventional drugs, (ii) delivery of novel drug classes, for example biomolecules and (iii) targeted delivery on the cellular/molecular level. Considering the solid foundation of experimental work, it does not take a large step outside the current box of thinking to follow the idea of using large carriers (>500 nm, unlikely to penetrate as a whole) for follicular penetration, retention and protection of sensitive compounds. Yet, reports on particles <200 nm being internalized by keratinocytes and dendritic cells at sites of barrier disruption (e.g., hair follicles) combined with recent advances in nanodermatology add interesting new facets to the possibilities carrier technologies could offer, for example, unprecedented levels of selectivity. The authors provide thought-provoking ideas on how smart delivery technologies and advances in our molecular understanding of hair pathophysiology could result in a whole new era of hair therapeutics. As the field still largely remains in preclinical investigation, determined efforts towards production of medical grade material and truly translational work are needed to demonstrate surplus value of carrier systems for clinical applications.

Amended final report of the safety assessment of cocamidopropylamine oxide.

Cocamidopropylamine Oxide is a tertiary amine oxide which functions as a hair-conditioning agent and as a surfactant, currently used in 60 cosmetic formulations at concentrations between 0.07% and 4.0%. In an earlier safety assessment, the Cosmetic Ingredient Review (CIR) Expert Panel had determined that the available data were insufficient to support the safety of this ingredient in cosmetic products. Additional data have now been provided and reviewed. Cocamidopropylamine Oxide was determined to have an acute oral LD(50) between 500 and 1000 mg/kg day(-1) using rats. The acute dermal LD(50) in rats was > 2174 mg/kg day(-1). A 28-day repeated oral dose toxicity study in rats found hemolytic anemia at 150 and 1000 mg/kg day(- 1), with a no observed effect level (NOEL) of 15 mg/kg day(- 1). At 5%, Cocamidopropylamine Oxide solution was not a primary dermal irritant. Application of 81.5% Cocamidopropylamine Oxide to rabbit skin caused moderate irritation under Draize classification scale, but 81.5% Cocamidopropylamine Oxide in rabbit eyes caused severe irritation. A maximization study classified Cocamidopropylamine Oxide as a nonsensitizer to guinea pig skin. Cocamidopropylamine Oxide was not mutagenic in an Ames test, with and without metabolic activation. No evidence of increased chromosomal aberrations were noted in human lymphocytes treated with 81.5% Cocamidopropylamine Oxide. In a clinical study, 7.5% Cocamidopropylamine Oxide was not a sensitizer, although it did produce some reactions typical of mild irritation. Although the impurities, amidoamine and dimethylaminopropylamine, have been implicated in contact allergy reactions to products containing cocamidopropylamine betaine, clinical testing of a product with cocamidopropylamine betaine containing these impurities, at levels comparable to those found in Cocamidopropylamine Oxide, failed to produce a reaction in 10 individuals known to be sensitive to cocamidopropylamine betaine. Two repeat-insult patch tests using a facial wash with 1% raw material containing 35% to 36.5% Cocamidopropylamine Oxide did not find evidence of dermal sensitization. Tests for dermal phototoxicity and photoallergenicity with the same facial wash product also did not produce evidence of effect. The CIR Expert Panel recognizes that there are data gaps regarding the use and concentration of this ingredient. However, the overall information available on types of products in which this ingredient is used and at what concentration indicate a pattern of use, which was considered by the Expert Panel in assessing safety. Overall, these data demonstrate that Cocamidopropylamine Oxide has low toxicity in animal and in vitro tests. Although there are no available carcinogenicity data, the available genotoxicity data, combined with the absence of any structural alerts, suggest no carcinogenic potential. The Panel noted the absence of reproductive and developmental toxicity data. Because this ingredient has a highly polarized molecular structure, the Panel considered that it would be, at most, slowly absorbed. Given that most of the uses and the highest use concentration of 4% is found in rinse-off products, the Panel determined that the available data suggest that Cocamidopropylamine Oxide is safe as used in rinse-off products. Although dermal penetration may be slow, data on the extent of dermal penetration of Cocamidopropylamine Oxide are needed to support the safety of leave-on uses. If there is significant dermal absorption, dermal reproductive and developmental toxicity data may be needed.

Experiencia clínica: análisis cuantitativo del cambio de videotricograma en pacientes chilenas con alopecia androgenética en respuesta a la utilización de una formulación a base de aminexil SP94® / Effect of a formulation using Aminexil SP94® in 48 chilean patients with androgenetic alopecia

Durante un período de 12 semanas se realizó un estudio clínico abierto, de tipo prospectivo, con el fin de evaluar la acción de una formulación a base de Aminexil SP94® en 48 pacientes con alopecia androgenética, diagnosticada clínicamente. Fue posible evaluar los efectos de la formulación sobre la fase anágena y telógena mediante la realización de videotricogramas, y conjuntamente se analizaron los efectos de la formulación sobre densidad capilar, sebumetría y presencia de halo-pericapilar. Se observó una mejoría significativa en cada uno de los parámetros medidos. Los efectos adversos se limitaron a la aparición de ardor en sólo un 4 por ciento de las pacientes, lo cual no derivó en la suspensión del tratamiento ni la eliminación del estudio. Se confirma la eficacia y seguridad de la formulación en el tratamiento de alopecia androgenética.

During twelve weeks, an open and prospective clinical study was performed in order to analyze the effect of a formulation using Aminexil SP94® in 48 patients with clinically diagnosed androgenetic alopecia. We evaluated effects during the telogen and anagen phase with video trichogram, and hair density, sebumetry and pericapillary halo were measured as well. There was a significant improvement in each of the parameters studied. Adverse effects were limited to mild itching in 4 percent of the patients. The efficacy and safety of the formulation in the treatment of androgenetic alopecia was confirmed.

Percutaneous penetration of diethanolamine through human skin in vitro: application from cosmetic vehicles.

Concern has been raised over the safety of diethanolamine (DEA) which may be present as a minor component of alkanolamide ingredients of cosmetic formulations. Skin penetration data were therefore generated for a range of typical formulations under in-use conditions. Seven rinse-off formulations (A-E, G and H), a leave-on emulsion (F), representing prototype cosmetic formulations and containing representative levels of DEA were prepared. Target levels of DEA were attained by inclusion of DEA as either (14)C-DEA or a combination of (14)C-DEA and unlabeled DEA. Skin permeation and distribution were evaluated using human skin in vitro, static diffusion cells and phosphate buffered saline (pH 7.4) as the receptor phase. At least 12 replicate epidermal membranes were prepared from a minimum of four donors for each test group. Receptor phase samples were taken at appropriate time intervals. At the end of the test period, radioactivity remaining on the skin surface and on the diffusion cell donor cap was determined before the skin samples were tape-stripped. The remaining tissue was solubilized and radioactivity determined. Permeation was very low from all vehicles applied under in-use conditions (range 1-48 ng/cm(2) over 24 h). Comparison was also made between permeation and distribution of DEA from an infinite dose of a simple aqueous solution and the leave-on formulation (F) through paired samples of fresh and frozen full thickness skin from the same donors. When applied as an infinite dose in aqueous solution DEA permeation at 24 h was greater through frozen than through fresh skin. From the leave-on formulation, permeation was similar and very low for both fresh and frozen skin. Recovery of DEA after application of the aqueous solution to fresh human skin and subsequent aqueous and organic extraction of the epidermal and dermal tissue indicated that the majority (>98%) of DEA was in the aqueous extract, suggesting that DEA was in the free state and not associated with the lipid fraction. These data provide a basis for the estimation of the potential systemic exposure and safety margins for DEA in representative cosmetic formulations.