Search

Background The objective of the present study was the investigation of hair follicle morphology in eight mammalian species in order to evaluate the species-specific contribution of hair follicles to skin penetration particularly with regard to the utilization of the different animal species as skin models for human skin. Methods Cyanoacrylate skin surface biopsy method (CSSB), light microscopy and also digital photography were used for the measurements of hair follicle morphology. Results The results revealed species-specific differences regarding the pattern of hair follicle distribution and also differences with regard to hair follicle parameters and characteristics. The results also showed that hair follicles generally possess enormous reservoir capacities, regarding the follicular volume. In all examined species, hair follicles reached at least one-fifth of stratum corneum storage capacity. The results were compared with human data obtained in a previous study. Conclusion With regard to hair follicle morphology and skin structure, the porcine skin seems to be the most appropriate skin model for human skin analog to previous investigations, whereas the skin of dog, cat, and rabbit showed the most significant differences. [ABSTRACT FROM AUTHOR]

Recent advances in the field of nanotechnology have allowed the manufacturing of elaborated nanometer-sized particles for various biomedical applications. A broad spectrum of particles, extending from various lipid nanostructures such as liposomes and solid lipid nanoparticles, to metal, nanocrystalline and polymer particles have already been tested as drug delivery systems in different animal models with remarkable results, promising an extensive commercialization in the coming years. Controlled drug release to skin and skin appendages, targeting of hair follicle-specific cell populations, transcutaneous vaccination and transdermal gene therapy are only a few of these new applications. Carrier systems of the new generation take advantage of improved skin penetration properties, depot effect with sustained drug release and of surface functionalization (e.g., the binding to specific ligands) allowing specific cellular and subcellular targeting. Drug delivery to skin by means of microparticles and nanocarriers could revolutionize the treatment of several skin disorders. However, the toxicological and environmental safety of micro- and nanoparticles has to be evaluated using specific toxicological studies prior to a wider implementation of the new technology. This review aims to give an overview of the most investigated applications of transcutaneously applied particle-based formulations in the fields of cosmetics and dermatology. [ABSTRACT FROM AUTHOR]

Recently, it has been demonstrated that particulate substances penetrate preferentially into the hair follicles and that the penetration depth depends on the particle size. In the present study, the influence of the vehicle of the particulate substances on the penetration depth was investigated. Four different formulations (ethanolic suspension, aqueous suspension, ethanolic gel and aqueous gel) containing peptide-loaded particles of 1 μm in diameter were prepared and applied on porcine ear skin. After penetration, punch biopsies were taken and the penetration depths of the particles were investigated by laser scanning microscopy. The deepest penetration was achieved with the gel formulations demonstrating an influence of the vehicle on the penetration depth of particulate substances. [ABSTRACT FROM AUTHOR]

Copyright of GMS Krankenhaushygiene Interdisziplinaer is the property of German Medical Science Publishing House gGmbH and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

What is already known about this subject • In recent years, it has been suggested that hair follicles represent important shunt routes into the skin for drugs and chemicals [ 1–3 ]. • In vitro studies have shown the importance of skin appendages for skin penetration by hydrophilic compounds [ 4 ]. Investigation of follicular penetration in vivo has been difficult due to the absence of appropriate analytical methods or suitable animal model systems. • Recently, a new method was described that quantifies follicular penetration in vivo by using selective closure of hair follicles [ 5 ]. • Caffeine is frequently used in skin penetration experiments as a model for highly water-soluble compounds. Occlusion [ 6 ] and skin thickness [ 7 ] seem to have little influence on the penetration of caffeine. However, percutaneous absorption rates for caffeine exhibit regional skin differences in humans in vivo[ 1 ]. What this study adds • The results of the present study demonstrate that a fast drug delivery of caffeine occurs through shunt routes. Therefore, hair follicles are considerable weak spots in our protective sheath against penetration into the body by hydrophilic substances. • We showed that there is a quantitative distinction between follicular penetration and interfollicular diffusion of caffeine in vivo. • These findings are of importance for the development and optimization of topically applied drugs and cosmetics. In addition, such properties must be considered in the development of skin protection measures. Aims The skin and its appendages are our protective shield against the environment and are necessary for the maintenance of homeostasis. Hypotheses concerning the penetration of substances into the skin have assumed diffusion through the lipid domains of the stratum corneum. It is believed that while hair follicles represent a weakness in the shield, they play a subordinate role in the percutaneous penetration processes. Previous investigation of follicular penetration has mostly addressed methodical and technical problems. Our study utilized a selective closure technique of hair follicle orifices in vivo, for the comparison of interfollicular and follicular absorption rates of caffeine in humans. Methods Every single hair follicle within a delimited area of skin was blocked with a microdrop of a special varnish-wax-mixture in vivo. Caffeine in solution was topically applied and transcutaneous absorption into the blood was measured by a new surface ionization mass spectrometry (SI/MS) technique, which enabled a clear distinction to be made between interfollicular and follicular penetration of a topically applied substance. Results Caffeine (3.75 ng ml−1) was detected in blood samples, 5 min after topical application, when the follicles remained open. When the follicles were blocked, caffeine was detectable after 20 min (2.45 ng ml−1). Highest values (11.75 ng caffeine ml−1) were found 1 h after application when the follicles were open. Conclusions Our findings demonstrate that hair follicles are considerable weak spots in our protective sheath against certain hydrophilic drugs and may allow a fast delivery of topically applied substances. [ABSTRACT FROM AUTHOR]

Previous studies suggest that drug delivery systems based on particles can be used to deposit active compounds in hair follicles and to target hair follicle-associated cell populations. The development of application protocols is complicated by the fact that there is no information available on the size and the position of key target structures in the different hair follicle types and their intra- and interindividual variation. Therefore, we performed morphometric measurements on histological sections of human terminal (THF) and vellus hair follicles (VHF) from the scalp and the retroauricular region. With 3864 ± 605 μm and 580 ± 84 μm in THF compared to 646 ± 140 μm and 225 ± 34 μm in VHF, the total length and the length of the infundibulum differed significantly as determined by paired t-test ( P < 0.0001). The same level of significance was observed for the position and the length of the bulge region. The thickness of the epithelial lining was lowest in VHF (45 ± 14 μm at 100 μm from skin surface) compared to 65 ± 20 μm at 150 μm in THF, while the thickness of the interfollicular epidermis ranged between 64 ± 12 μm and 99 ± 18 μm in VHF-bearing skin and 72 ± 16 μm and 136 ± 37 μm in THF-bearing skin. In addition, the diameter of the hair follicle opening was determined at 50 μm intervals from the skin surface. Our data suggest that hair follicle types in defined body regions represent rather homogenous groups and that particle-based drug delivery may be a feasible approach, also in larger numbers of individuals. We provide precise information on the size and the position of key target structures in VHF and THF. [ABSTRACT FROM AUTHOR]

Cutaneous characteristics, e.g., thickness of the SC and density of follicles, affect the penetration of topically applied substances. In the present study, the penetration of benzyl nicotinate, causing a vasodilation, was studied on three anatomic sites (forearm, forehead and calf) differing in their skin characteristics. Therefore, the blood flow of the superficial dermal plexus and that of the larger capillaries in the deeper skin layers was simultaneously measured using a laser Doppler flowmeter. In addition, the cutaneous temperature and redness were determined as a function of time. These four biological reactions were measured in turn on a skin area treated with a gel containing benzyl nicotinate and on an untreated control area. The highest basal levels were observed on the forehead. Topical application of benzyl nicotinate resulted in an increase in each biological response. Compared to the other sites, the maximal values were reached earliest on the forehead, which also showed the fastest decrease. No significant differences were obtained comparing the kinetic data of the calf with that of the forearm. The results indicate an additional contribution by the numerous vellus hair follicles of the forehead to the penetration and exposure of the drug. [ABSTRACT FROM AUTHOR]

Investigations into the penetration pathways of topically applied substances through the skin play an important role in dermatological science. Recently, the hair follicles have increasingly been recognized as an important pathway for percutaneous penetration, although the role of the follicles has still not been clarified in detail. Therefore, the aim of the present study was to develop an in vivo method for the analysis of the follicular rate of penetration processes. In order to reach this goal, the follicles were excluded from the penetration process of topically applied substances. Different study designs were evaluated, and we were able to show that the application of nail varnish to each follicular orifice represents an effective method of blocking the follicles selectively against the penetration of topically applied substances. In dermatological science, there is new information on the physiology of skin penetration processes, thus allowing examination of the follicular rate of penetration and improvement of the pharmacokinetics of topically applied substances. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Hair follicles represent reservoirs for localized drug therapy and transport pathways for systemic drug delivery. This study describes an approach towards developing a novel procedure for quantifying topically applied substances located in the hair follicles of porcine ear skin, a model for human in vivo skin, using a fluorescent dye. Approximately 5% of the topically applied dye was recovered from the hair follicles, which is in accordance with a previous study. [ABSTRACT FROM AUTHOR]

In recent years, hair follicles have attracted much attention in several fields of research. Representing complex and dynamic three-dimensional structures, which undergo highly specific growth cycles, the hair follicles are susceptible to several disturbances, for example, infectious diseases, various forms of hair loss, autoimmune diseases, androgen-associated diseases and skin tumors. Consequently, they are increasingly considered to be relevant drug targets and to represent drug delivery routes through the stratum corneum into deeper skin layers. The effectiveness of follicular or even transfollicular penetration depends on not only the penetrating substance or on its vehicle, but also on follicular density, size and reservoir, as well as on the activity status of the hair follicle. Follicular targeting, ideally topical delivery of substances to specific compartments and cell populations within the hair follicles, offers opportunities in the treatment of hair follicle-associated diseases, immunotherapy and even gene therapy, as the bulge region of the hair follicle represents a reservoir of stem cells. This present paper gives an overview of the recent developments in the fascinating field of hair follicles, their disorders and their opportunities. [Copyright &y& Elsevier]

Abstract: Particulate drug delivery via hair follicles represents a promising concept, although requirements are high. This process must be realized at the desired depth and at the appropriate time, due to the fact that the particles themselves are not able to overcome the follicular skin barrier. In the present study, a novel triggering concept for the release of a model drug from the delivering particles is presented based on the application of two different particle types of the same size, where one particle type is the drug carrier, and the second one is loaded with a protease. The latter particle type is supposed to interact with the drug-carrying particles to trigger the drug release. A mixture of both particles was applied onto porcine skin samples, followed by follicular analysis. As a control, the particles were applied unaided without protease, whereas one skin area remained untreated. The investigations revealed that the protease was able to release the model drug from the delivering particles in significant depths within the hair follicle (866±62nm). Additionally, an uptake of the model drug in the sebaceous gland was observed after release providing a promising novel approach for the development of treatment strategies for different skin diseases. [Copyright &y& Elsevier]

Abstract: Particle-based drug delivery systems allow the controlled and targeted release of incorporated active compounds to the skin and are promising tools to improve the efficacy of topical therapies. In this study we investigated the stability and release properties of biodegradable polylactic acid (PLA) particles upon topical application on human skin explants. PLA particles loaded with the hydrophilic fluorochrome 4-Di-2-Asp (DiAsp-PLA) were compared to PLA particles loaded with the lipophilic fluorochrome Bodipy 630/650 (BP-PLA). Changes of the particle morphology after their incubation on skin surface were investigated by means of electron microscopy while fluorescence microscopy and flow cytometry were used to evaluate particle penetration in hair follicles and fluorochrome release. We found that BP-PLA particles released rapidly the loaded fluorochrome and lost the particulate morphology within a few hours after application on skin surface. On the contrary, DiAsp-PLA particles maintained the particulate morphology, accumulated in hair follicles, and allowed a constant release of the incorporated fluorochrome for up to 16h. These results show that, once applied to skin surface, PLA particles release the incorporated fluorochromes in a time-dependent manner and suggest the perspective to modulate particle stability and release properties by incorporating excipients with different degree of lipophilicity. [Copyright &y& Elsevier]

Abstract: Recently, it was demonstrated that particles could be utilized as carrier systems for drugs into the hair follicles. In the present study, a two-component drug delivery system is presented consisting of degradable particles loaded with fluorescein isothiocyanate and a separate protease formulation for degradation. The particles were applied alone, 30min previous to the protease application and simultaneously with the protease onto porcine skin. Subsequently, biopsies were removed, and the penetration depths of the particles were analyzed using laser scanning microscopy. The obtained results demonstrate that the particles alone achieved a penetration depth of around 900μm. Similar results were obtained for the successive application of particles and protease, whereas a release of the fluorescent dye was only observed in the upper 250μm corresponding to the penetration depth of the protease. In the case of the simultaneous application, the particles were partly dissolved before application, leading to a reduced particle size and diminished penetration depth. The results revealed that degradable particles are a promising tool for drug delivery into the skin. [Copyright &y& Elsevier]

Abstract: Hair follicles represent interesting target sites for topically applied substances such as topical vaccinations or agents used in the field of regenerative medicine. In recent years, it could be shown that particles penetrate very effectively into the hair follicles. In the present study, the influence of particle size on the follicular penetration depths was examined. The penetration depths of two different types of particles sized 122 to 1000nm were determined in vitro on porcine skin. The results revealed that the particles of medium size (643 and 646nm, respectively) penetrated deeper into the porcine hair follicles than smaller or larger particles. It was concluded that by varying the particle size, different sites within the porcine hair follicle can be targeted selectively. For the human terminal hair follicle, the situation can be expected to be similar due to a similar size ratio of the hair follicles. [Copyright &y& Elsevier]

Particle-based drug delivery systems target active compounds to the hair follicle and may result in a better penetration and higher efficiency of compound uptake by skin resident cells. As previously proposed, such delivery systems could be important tools for vaccine delivery. In this study, we investigated the penetration of solid fluorescent 40 or 200 nm polystyrene nanoparticles (NPs) as well as virus particles in murine skin to further investigate the efficacy of transcutaneously (TC) applied particulate vaccine delivery route. We demonstrated that 40 and 200 nm NPs and modified vaccinia Ankara (MVA) expressing the green-fluorescent protein penetrated deeply into hair follicles and were internalized by perifollicular antigen-presenting cells (APCs). Fibered-based confocal microscopy analyses allowed visualizing in vivo particle penetration along the follicular duct, diffusion into the surrounding tissue, uptake by APCs and transport to the draining lymph nodes. The application of small particles, such as ovalbumin coding DNA or MVA, induced both humoral and cellular immune responses. Furthermore, TC applied MVA induced protection against vaccinia virus challenge. Our results strengthen the concept of TC targeting of cutaneous APCs by hair follicles and will contribute to the development of advanced vaccination protocols using NPs or viral vectors.Journal of Investigative Dermatology (2009) 129, 1156–1164; doi:10.1038/jid.2008.356; published online 4 December 2008 [ABSTRACT FROM AUTHOR]

Abstract: The important role of hair follicles as penetration pathways and reservoir structures for topically applied compounds has been validated in numerous animal models as well as in humans. Follicular penetration rates are modulated by regional variations in size and proportions and the functional status. Advances have especially been made in the targeting of hair follicle-associated cell populations including antigen-presenting cells and stem cells. Improved investigative methods based on differential stripping, spectrophotometry and confocal laser scanning microscopy have led to the determination of the penetration profiles and kinetics for a multiplicity of drugs and drug delivery systems. The observation that particulate delivery systems aggregate and remain in hair follicle openings and their penetration along the follicular duct occurs in a size-dependent manner, which has led to advanced concepts of targeted drug delivery of bioactive compounds in the field of solid particles, as well as semi-solid particles, such as liposomes. This review summarizes the recent progress in this field, and underlines the necessity for pilot studies in human volunteers to further the development of clinical applications for follicular targeting. [Copyright &y& Elsevier]

Abstract: Penetration studies are commonly performed on in vitro models, presumably due to a lack of non-invasive in vivo methods. To date, it is not clear whether in vitro models are suitable to reflect the in vivo conditions for percutaneous penetration. Apart from inter and intraspecies skin differences, the excision of a skin sample may influence the penetration rate inter alia as a result of the contraction of the elastic fibres in the skin during excision. Therefore, the aim of the present study was to investigate the follicular reservoir of the hair follicles of human skin in vivo and in vitro utilizing the method of differential stripping. The results obtained revealed a significantly reduced follicular reservoir in vitro, which was only 9.5±10.6% of the in vivo reservoir. These results are important for the interpretation of earlier and future penetration investigations. It can thus be assumed that excised skin models are suitable for penetration studies only to a limited extent, as follicular penetration is greatly diminished due to the contraction of the elastic fibres of the skin. [Copyright &y& Elsevier]

Abstract: The penetration and storage behavior of dye-containing nanoparticles (diameter 320nm) 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]