Variations of Hair Follicle Size and Distribution in Different Body Sites

For the evaluation and quantification of follicular penetration processes, the knowledge of variations of hair follicle parameters in different body sites is basic. Characteristics of follicle sizes and potential follicular reservoir were determined in cyanoacrylate skin surface biopsies, taken from seven different skin areas (lateral forehead, back, thorax, upper arm, forearm, thigh, and calf region). The highest hair follicle density and percentage of follicular orifices on the skin surface and infundibular surface were found on the forehead, whereas the highest average size of the follicular orifices was measured in the calf region. The highest infundibular volume and therefore a potential follicular reservoir was calculated for the forehead and for the calf region, although the calf region showed the lowest hair follicle density. The calculated follicular volume of these two skin areas was as high as the estimated reservoir of the stratum corneum. The lowest values for every other parameter were found on the forearm. The present investigation clearly contradicts former hypothesis that the amount of appendages of the total skin surface represents not more than 0.1%. Every body region disposes its own hair follicle characteristics, which, in the future, should lead us to a differential evaluation of skin penetration processes and a completely different understanding of penetration of topically applied drugs and cosmetics

Water-filtered infrared-A (wIRA) can act as a penetration enhancer for topically applied substances

Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone

Wassergefiltertes Infrarot A (wIRA) kann als Penetrationsverstärker für topisch aufgetragene Substanzen wirken

Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone. Aim of the study: Investigation of the influence of wIRA irradiation on the dermatopharmacokinetics of topically applied substances by use of optical methods, especially to localize penetrating substances, in a prospective randomised controlled study in humans. Methods: The penetration profiles of the hydrophilic dye fluorescein and the lipophilic dye curcumin in separate standard water-in-oil emulsions were determined on the inner forearm of test persons by tape stripping in combination with spectroscopic measurements. Additionally, the penetration was investigated in vivo by laser scanning microscopy. Transepidermal water loss, hydration of the epidermis, and surface temperature were determined. Three different procedures (modes A, B, C) were used in a randomised order on three separate days of investigation in each of 12 test persons. In mode A, the two dyes were applied on different skin areas without water-filtered infrared-A (wIRA) irradiation. In mode B, the skin surface was irradiated with wIRA over 30 min before application of the two dyes (Hydrosun® radiator type 501, 10 mm water cuvette, orange filter OG590, water-filtered spectrum: 590–1400 nm with dominant amount of wIRA). In mode C, the two dyes were applied and immediately afterwards the skin was irradiated with wIRA over 30 min. In all modes, tape stripping started 30 min after application of the formulations. Main variable of interest was the ratio of the amount of the dye in the deeper (second) 10% of the stratum corneum to the amount of the dye in the upper 10% of the stratum corneum. Results: The penetration profiles of the hydrophilic fluorescein showed in case of pretreatment or treatment with wIRA (modes B and C) an increased penetration depth compared to the non-irradiated skin (mode A): The ratio of the amount of the dye in the deeper (second) 10% of the stratum corneum to the amount of the dye in the upper 10% of the stratum corneum showed medians and interquartile ranges for mode A of 0.017 (0.007/0.050), for mode B of 0.084 (0.021/0.106), for mode C of 0.104 (0.069/0.192) (difference between modes: p=0.0112, significant; comparison mode A with mode C: p<0.01, significant). In contrast to fluorescein, the lipophilic curcumin showed no differences in the penetration kinetics, in reference to whether the skin was irradiated with wIRA or not. These effects were confirmed by laser scanning microscopy. Water-filtered infrared-A irradiation increased the hydration of the stratum corneum: transepidermal water loss rose from approximately 8.8 g m-2 h-1 before wIRA irradiation to 14.2 g m-2 h-1 after wIRA irradiation and skin hydration rose from 67 to 87 relative units. Skin surface temperature increased from 32.8°C before wIRA to 36.4°C after wIRA irradiation. Discussion: The better penetration of the hydrophilic dye fluorescein after or during skin irradiation (modes B and C) can be explained by increased hydration of the stratum corneum by irradiation with wIRA. Conclusions: As most topically applied substances for the treatment of patients are mainly hydrophilic, wIRA can be used to improve the penetration of substances before or after application of substances – in the first case even of thermolabile substances – with a broad clinical relevance as a contact free alternative to an occlusive dressing.Hintergrund: Für Bestrahlungen mit wassergefiltertem Infrarot A (wIRA) wurde durch die Untersuchung funktioneller Effekte penetrierter Substanzen, wie Vasokonstriktion durch Kortison, am Menschen gezeigt, dass sie die Penetration von klinisch verwendeten topisch aufgebrachten Stoffen verbessern. Ziele der Studie: Untersuchung des Einflusses von wIRA-Bestrahlung auf die Dermatopharmakokinetik von topisch angewandten Stoffen unter Verwendung von optischen Methoden, insbesondere zum Lokalisieren von penetrierenden Stoffen, in einer prospektiven randomisierten, kontrollierten Studie am Menschen. Methoden: Die Penetrationsprofile des hydrophilen Farbstoffs Fluoreszein und des lipophilen Farbstoffs Curcumin in separaten Standard-Wasser-in-Öl-Emulsionen wurden auf der Innenseite des Unterarms von Probanden mit der Tape-Stripping-Methode in Verbindung mit spektroskopischen Messungen bestimmt. Außerdem wurde die Penetration in vivo mittels Laser-Scan-Mikroskopie untersucht. Zudem wurden der transepidermale Wasserverlust, die Hydratation der Epidermis und die Oberflächentemperatur gemessen. Drei verschiedene Verfahren (Modi A, B, C) wurden in randomisierter Reihenfolge an drei separaten Untersuchungstagen bei jedem der 12 Testpersonen verwendet. Beim Modus A wurden die zwei Farbstoffe ohne Bestrahlung mit wassergefiltertem Infrarot A (wIRA) auf separate Hautareale aufgetragen. Beim Modus B wurde die Hautoberfläche vor dem Auftragen der zwei Farbstoffe 30 min lang mit wIRA bestrahlt (Hydrosun®-Strahler, Typ 501, 10 mm Wasserküvette, Orangefilter OG590, wassergefiltertes Spektrum: 590–1400 nm mit dominantem Anteil an wIRA). Beim Modus C wurde unmittelbar nach dem Auftragen der Farbstoffe die Haut 30 min lang mit wIRA bestrahlt. Bei allen Modi begann das Tape-Stripping 30 min nach dem Auftragen der Formulierungen. Hauptzielvariable war das Verhältnis der Menge an Farbstoff in den tieferen (zweiten) 10% des Stratum corneum zur Menge an Farbstoff in den oberen 10% des Stratum corneum. Ergebnisse: Die Penetrationsprofile des hydrophilen Fluoreszeins zeigten bei Vorbehandlung oder Behandlung mit wIRA (Modi B und C) eine gesteigerte Penetrationstiefe im Vergleich zu nicht bestrahlter Haut (Modus A): Das Verhältnis der Menge an Farbstoff in den tieferen (zweiten) 10% des Stratum corneum zur Menge an Farbstoff in den oberen 10% des Stratum corneum zeigte Mediane und Interquartilspannen für Modus A von 0,017 (0,007/0,050), für Modus B von 0,084 (0,021/0,106), für Modus C von 0,104 (0,069/0,192) (Unterschied zwischen den Modi: p=0,0112, signifikant; Vergleich von Modus A mit Modus C: p<0,01, signifikant). Im Gegensatz zum Fluoreszein zeigte das lipophile Curcumin keine Unterschiede in der Penetrationskinetik in Abhängigkeit davon, ob die Haut mit wIRA bestrahlt wurde oder nicht. Diese Effekte wurden durch die Laser-Scan-Mikroskopie-Ergebnisse bestätigt. Bestrahlung mit wassergefiltertem Infrarot A steigerte die Hydratation des Stratum corneum: Der transepidermale Wasserverlust nahm von etwa 8,8 g m-2 h-1 vor wIRA-Bestrahlung auf 14,2 g m-2 h-1 nach wIRA-Bestrahlung zu, und die Hauthydratation stieg von 67 auf 87 relative Einheiten. Die Temperatur an der Hautoberfläche stieg von 32,8°C vor wIRA auf 36,4°C nach wIRA-Bestrahlung. Diskussion: Die bessere Penetration des hydrophilen Farbstoffs Fluoreszein nach oder während Bestrahlung der Haut (Modi B und C) kann mit der gesteigerten Hydratation des Stratum corneum durch die wIRA-Bestrahlung erklärt werden. Folgerungen: Da die meisten topisch aufgetragenen Substanzen für die Behandlung von Patienten hauptsächlich hydrophil sind, kann wIRA verwendet werden, um die Penetration von Stoffen vor oder nach dem Auftragen der Stoffe – im ersten Fall sogar von hitzeempfindlichen Stoffen – mit einer breiten klinischen Relevanz als kontaktfreie Alternative zum Okklusivverband zu verbessern

Nanoparticles - An efficient carrier for drug delivery into the hair follicles

The penetration and storage behavior of dye-containing nanoparticles (diameter 320 nm) into the hair follicles was investigated. The results were compared to the findings obtained with the same amount of dye in the non-particle form. In the first part of the experiments, the penetration of the dye into the hair follicles was investigated in vitro on porcine skin, which is an appropriate model for human tissue. It was found that the nanoparticles penetrate much deeper into the hair follicles than the dye in the non-particle form, if a massage had been applied. Without massage, similar results were obtained for both formulations. Subsequently, the storage behavior of both formulations in the hair follicles was analyzed in vivo on human skin by differential stripping. Using the same application protocol, the nanoparticles were stored in the hair follicles up to 10 days, while the non-particle form could be detected only up to 4 days. Taking into consideration the surface structure of the hair follicles, it was assumed that the movement of the hairs may act as a pumping mechanism pushing the nanoparticles deep into the hair follicles