Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects.

The treatment of various hair disorders has become a central focus of good dermatologic patient care as it affects men and women all over the world. For many inflammatory-based scalp diseases, glucocorticoids are an essential part of treatment, even though they are known to cause systemic as well as local adverse effects when applied topically. Therefore, efficient targeting and avoidance of these side effects are of utmost importance. Optimizing the balance between drug release, interfollicular permeation, and follicular uptake may allow minimizing these adverse events and simultaneously improve drug delivery, given that one succeeds in targeting a sustained release formulation to the hair follicle. To test this hypothesis, three types of polymeric nanocarriers (nanospheres, nanocapsules, lipid-core nanocapsules) for the potent glucocorticoid clobetasol propionate (CP) were prepared. They all exhibited a sustained release of drug, as was desired. The particles were formulated as a dispersion and hydrogel and (partially) labeled with Rhodamin B for quantification purposes. Follicular uptake was investigated using the Differential Stripping method and was found highest for nanocapsules in dispersion after application of massage. Moreover, the active ingredient (CP) as well as the nanocarrier (Rhodamin B labeled polymer) recovered in the hair follicle were measured simultaneously, revealing an equivalent uptake of both. In contrast, only negligible amounts of CP could be detected in the hair follicle when applied as free drug in solution or hydrogel, regardless of any massage. Skin permeation experiments using heat-separated human epidermis mounted in Franz Diffusion cells revealed equivalent reduced transdermal permeability for all nanocarriers in comparison to application of the free drug. Combining these results, nanocapsules formulated as an aqueous dispersion and applied by massage appeare to be a good candidate to maximize follicular targeting and minimize drug penetration into the interfollicular epidermis. We conclude that such nanotechnology-based formulations provide a viable strategy for more efficient drug delivery to the hair follicle. Moreover, they present a way to minimize adverse effects of potent glucocorticoids by releasing the drug in a controlled manner and simultaneously decreasing interfollicular permeation, offering an advantage over conventional formulations for inflammatory-based skin/scalp diseases.

Statistical comparison of dissolution profiles to predict the bioequivalence of extended release formulations.

Appropriate setting of dissolution specification of extended release (ER) formulations should include precise definition of a multidimensional space of complex definition and interpretation, including limits in dissolution parameters, lag time (t-lag), variability, and goodness of fit. This study aimed to set dissolution specifications of ER by developing drug-specific dissolution profile comparison tests (DPC tests) that are able to detect differences in release profiles between ER formulations that represent a lack of bioequivalence (BE). Dissolution profiles of test formulations were simulated using the Weibull and Hill models. Differential equations based in vivo-in vitro correlation (IVIVC) models were used to simulate plasma concentrations. BE trial simulations were employed to find the formulations likely to be declared bioequivalent and nonbioequivalent (BE space). Customization of DPC tests was made by adjusting the delta of a recently described tolerated difference test (TDT) or the limits of rejection of f2. Drug ka (especially if ka is small), formulation lag time (t-lag), the number of subjects included in the BE studies, and the number of sampled time points in the DPC test were the factors that affected the most these setups of dissolution specifications. Another recently described DPC test, permutation test (PT), showed excellent statistical power. All the formulations declared as similar with PT were also bioequivalent. Similar case-specific studies may support the biowaiving of ER drug formulations based on customized DPC tests.

Quantification of nanoparticle uptake into hair follicles in pig ear and human forearm.

Drug delivery via the hair follicle (HF) especially with nanoparticles (NP) recently gained attention due to a depot effect and facilitated absorption conditions within the lower HF. With the prospect of transdermal drug delivery, it is of interest to optimize the follicular uptake of NP. In this study, a method was developed to quantify NP uptake into HF and applied in vitro in a pig ear model and in vivo in human volunteers. The influence of NP material on HF uptake was investigated using fluorescence-labeled NP based on poly(D,L-lactide-co-glycolide) (PLGA). All NP had similar hydrodynamic sizes (163-170 nm) but different surface modifications: (i) plain PLGA, (ii) chitosan-coated PLGA (Chit.-PLGA), and (iii) Chit.-PLGA coated with different phospholipids (PL) (DPPC (100), DPPC:Chol (85:15), and DPPC:DOTAP (92:8). Differential stripping was performed, including complete mass balance. The samples were extracted for fluorescence quantification. An effect of the PL coating on follicular uptake was observed as DPPC (100) and DPPC:DOTAP (92:8) penetrated into HF to a higher extent than the other tested NP. The effect was observed both in the pig ear model as well as in human volunteers, although it was statistically significant only in the in vitro model. An excellent in vitro-in vivo correlation (IVIVC, r(2)=0.987) between both models was demonstrated, further supporting the suitability of the pig ear model as a surrogate for the in vivo situation in humans for quantifying NP uptake into HF. These findings may help to optimize NP for targeting the HF and to improve transdermal delivery.

From the structure of the skin barrier and dermal formulations to in vitro transport models for skin absorption: skin research in the Netherlands and in Germany.

This review presents an overview of German and Dutch research institutions and their studies in the field of skin drug delivery and adjacent topics. In the Netherlands, the involved research groups are mainly localized in Leiden, whereas in Germany the skin research institutions are spread over the whole country. The scientific studies in the Netherlands focus on the in-depth analysis of human skin composition and its individual components as well as on the development and characterization of dermal drug delivery systems ranging from liquid crystalline systems and vesicles up to microneedles with an emphasis on examining the interactions of these drug delivery systems with the human skin in vitro and in vivo. In Germany, the individual areas of research span from in-depth investigations on various drug delivery systems intended for skin application and the development of novel in vitro models for skin absorption testing up to in vivo studies focusing on the biological performance of topically applied actives. Furthermore, sophisticated analytical techniques are applied for the elucidation of skin assembly and transport processes. In addition, experimentally derived data are correlated with advanced computational modelling. Even though the individual research topics in the Netherlands and Germany are quite diverse, the exchange of knowledge and interdisciplinary collaborations between the two neighbouring countries were and are still frequently made. In this context, the review aims at highlighting crosslinks between the different institutions and individual persons to complete the picture. For each institution, the principal investigators and their studies are presented and the upcoming young scientists are introduced as an outlook for the field. This review does not claim completeness, but is rather intended to give a general overview of Dutch and German research in the field of skin drug delivery and adjacent topics.

Finite dose skin mass balance including the lateral part: comparison between experiment, pharmacokinetic modeling and diffusion models.

This work investigates in vitro finite dose skin absorption of the model compounds flufenamic acid and caffeine experimentally and mathematically. The mass balance in different skin compartments (donor, stratum corneum (SC), deeper skin layers (DSL), lateral skin parts and acceptor) is analyzed as a function of time. For both substances high amounts were found in the lateral skin compartment after 6h of incubation, which emphasizes not to elide these parts in the modeling. Here, three different mathematical models were investigated and tested with the experimental data: a pharmacokinetic model (PK), a detailed microscopic two-dimensional diffusion model (MICRO) and a macroscopic homogenized diffusion model (MACRO). While the PK model was fitted to the experimental data, the MICRO and the MACRO models employed input parameters derived from infinite dose studies to predict the underlying diffusion process. All models could satisfyingly predict or describe the experimental data. The PK model and MACRO model also feature the lateral parts.

Pulmonary delivery and tissue distribution of aerosolized antisense 2'-O-Methyl RNA containing nanoplexes in the isolated perfused and ventilated rat lung.

Pulmonary delivery of drugs, particularly in the treatment of lung cancer, is an attractive strategy for future targeted therapy. In this context, inhalation of nanoplexes might offer a new mode for drug delivery in gene therapy. However, limited data are currently available demonstrating pulmonary delivery, cellular uptake as well as local tolerability in lung tissue. The aim of this study was to elucidate the pulmonary delivery, tissue distribution and local tolerability of aerosolized chitosan-coated poly(lactide-co-glycolide) based nanoplexes containing antisense 2'-O-Methyl RNA (OMR). Therefore, an aerosol of OMR-nanoplexes or OMR alone was administered intra-tracheally using the model of the isolated perfused and ventilated rat lung. Localization of OMR in rat lung tissue was examined by immunohistochemistry. Administration of the OMR-nanoplex formulation resulted in significantly higher cellular OMR uptake of the respiratory epithelium in contrast to the administration of OMR alone, indicating that drug administration via aerosolized nanoplexes is able to target lung tissue. No prominent changes in lung physiology parameters were observed following inhalation, suggesting good local tolerability of OMR-nanoplex formulation.

Treatment of lung cancer via telomerase inhibition: self-assembled nanoplexes versus polymeric nanoparticles as vectors for 2'-O-Methyl-RNA.

Antisense oligonucleotide, 2'-O-Methyl-RNA (OMR), is known as potent telomerase inhibitor for the treatment of lung cancer but limited by poor intracellular uptake. Chitosan-coated polymeric nanoparticles were compared to chitosan solution as non-viral vectors for OMR. The study investigated the role of chitosan properties and concentration in improving the efficiency of the nanocarriers in terms of loading, viability, cellular uptake, and telomerase inhibition in human lung cancer cell lines. Certain concentration of chitosan on nanoparticle surface is necessary to significantly increase the cellular uptake. However, excessive chitosan negatively affected the transfection efficiency. Self-assembled nanoplexes with chitosan polymer are preferentially adsorbed to the cell membrane rather than being internalized. Thus, polymeric nanoparticles proved to be superior to cationic polymers as carrier for antisense oligonucleotides. Charge cannot be considered the principle factor behind improved transfection. Uptake studies carried out on air-interface cell cultures to mimic in vivo conditions supported the results on normal cultures showing enhanced uptake of nanoplexes over naked oligonucleotides. OMR nanoplexes reduced telomerase activity by ∼50% in A549 cells concluding the potential of the system as a safe, non-invasive, and efficient treatment for lung carcinoma. These data are prerequisites for the ongoing studies on lung perfusion model and in vivo experiments.

Telomerase as an emerging target to fight cancer--opportunities and challenges for nanomedicine.

Telomerase as an enzyme is responsible for the renewal of the chromosomal ends, the so-called telomeres. By preventing them from shortening with each cell cycle, telomerase is able to inhibit cellular senescence and apoptosis. Telomerase activity, which is detectable in the majority of cancer cells, allows them to maintain their proliferative capacity. The thus obtained immortality of those cells again is a key to their malignancy. Based on these discoveries, it is obvious that telomerase inhibitors would represent an innovative approach to fight cancer, and a variety of such candidate molecules are currently in the pipeline. Telomerase inhibitors largely fall in two classes of compounds: small synthetic molecules and nucleotide-based biologicals. For several candidates, some proof of concept studies have been demonstrated, either on cell cultures or in animal models. But the same studies also revealed that inefficient delivery is largely limiting the translational step into the clinic. The most appealing feature of telomerase inhibitors, which distinguishes them from conventional anticancer drugs, is probably seen in their intrinsic non-toxicity to normal cells. Nevertheless, efficient delivery to the target cells, i.e. to the tumor, is still required. Here, some well-known biopharmaceutical problems such as insufficient solubility, permeability or even metabolic stability are frequently encountered. To address these challenges, there is a clear need for adequate delivery technologies, for example by using nanomedicines, that would allow to overcome their biopharmaceutical shortcomings and to warrant a sufficient bioavailability at the target side. This review first briefly explains the concept of telomerase and telomerase inhibition in cancer therapy. It secondly aims to provide an overview of the different currently known telomerase inhibitors. Finally, the biopharmaceutical limitations of these molecules are discussed as well as the possibilities to overcome those limits by novel drug carrier systems and formulation approaches.

Comparative study on the in vitro human skin permeation of monoterpenes and phenylpropanoids applied in rose oil and in form of neat single compounds.

Essential oils are ingredients of cosmetic and health care products as well as massage oil used in aromatherapy. There is no doubt that essential oils and their components are able to permeate human skin. But information is rare dealing with percutanous absorption of essential oils in more detail. In this paper we investigated the in vitro skin permeation of monoterpenes and phenylpropanoids applied in pure rose oil and in form of neat single substances. We found that the application form had an exceeding influence on the skin permeation behaviour of the compounds. For substances applied in rose oil a clear relationship between their lipophilic character, chemical structure, and skin permeation could be confirmed. Regarding the P(app)-values the substances are ranked in the order: monoterpene hydrocarbons < monoterpene alcohols < monoterpene ketons < phenylpropanoids. In contrast, for neat single substances there were no relationships between their lipophilic characters, structures and skin permeation. Furthermore, except for alpha-pinene and isomenthone, the P(app)-values of all other substances were several times higher when applied in pure native rose oil than in their neat form. This suggests that co-operative interactions between essential oil components may promote skin permeation behaviour of essential oil and its components.

Infrared densitometry: a fast and non-destructive method for exact stratum corneum depth calculation for in vitro tape-stripping.

The investigation of drug penetration into the stratum corneum (SC) by tape-stripping requires an accurate measure of the amount of SC on each tape-strip in order to determine the depth inside the SC. This study applies infrared densitometry (IR-D) to in vitro tape-stripping using the novel Squame Scan(R) 850A. The device had recently been shown to provide accurate measurements of the SC depth for tape-stripping in vivo. Furthermore, the suitability of IR-D for determining the endpoint of tape-stripping, i.e. complete SC removal, was tested. The SC depth was computed from the IR-D data of sequential tape-strips and compared to the results of a protein assay as gold standard. IR-D provided accurate depth results both for freshly excised skin and for skin stored frozen for up to 3 months. In addition, the lower limit of quantification of IR-D indicates the complete removal of the SC (less than 5% of the total SC remaining) and can be used for adjusting the number of tapes applied in situ. Therefore, IR-D is an accurate, fast and non-destructive method for SC depth determination.

Nanoparticles made from novel starch derivatives for transdermal drug delivery.

The goal of this paper was aimed to the formulation of nanoparticles by using two different propyl-starch derivatives - referred to as PS-1 and PS-1.45 - with high degrees of substitution: 1.05 and 1.45 respectively. A simple o/w emulsion diffusion technique, avoiding the use of hazardous solvents such as dichloromethane or dimethyl sulfoxide, was chosen to formulate nanoparticles with both polymers, producing the PS-1 and PS-1.45 nanoparticles. Once the nanoparticles were prepared, a deep physicochemical characterization was carried out, including the evaluation of nanoparticles stability and applicability for lyophilization. Depending on this information, rules on the formation of PS-1 and PS-1.45 nanoparticles could be developed. Encapsulation and release properties of these nanoparticles were studied, showing high encapsulation efficiency for three tested drugs (flufenamic acid, testosterone and caffeine); in addition a close to linear release profile was observed for hydrophobic drugs with a null initial burst effect. Finally, the potential use of these nanoparticles as transdermal drug delivery systems was also tested, displaying a clear enhancer effect for flufenamic acid.

Nortriptyline for smoking cessation: release and human skin diffusion from patches.

The objective of this work was to develop a simple and inexpensive transdermal formulation containing Nortriptyline Hydrochloride (NTH) for smoking cessation support therapy. Hydroxypropyl-methyl-cellulose was chosen as polymer and a mixture of transdermal enhancers (selected from previous research) was incorporated. The formulations were characterised in terms of appearance, thickness, uniformity of NTH content, release and skin permeation. Release studies demonstrated controlled release for four formulations. Diffusion studies were performed through human heat separated epidermis (HHSE) using Franz Diffusion Cells (FDC). Patches provided different fluxes varying from 20.39+/-7.09 microg/(cm(2) h) to 256.19+/-94.62 microg/(cm(2) h). The penetration profiles of NTH within the stratum corneum (SC) and deeper skin layers (DSL) were established after three administration periods (3 h, 6 h, and 24 h). Skin changes induced by the application of the patches were observed by confocal laser scanning microscopy (CLSM). The highest flux obtained would provide the recommended doses for smoke cessation support therapy (25-75 mg per day) with a 2 cm x 2 cm patch or a 3.5 cm x 3.5 cm patch, respectively, without skin damage evidence.

The influence of chitosan content in cationic chitosan/PLGA nanoparticles on the delivery efficiency of antisense 2'-O-methyl-RNA directed against telomerase in lung cancer cells.

Tailorable cationic chitosan/PLGA nanoparticles (CPNP) were used for the delivery of an antisense 2'-O-methyl-RNA (2OMR) directed against RNA template of human telomerase. Here, we describe the influence of the chitosan content on binding efficiency, complex stability, uptake in different human lung cell types and finally demonstrate the efficacy of this nanoplex system. CPNPs were prepared by the emulsion-solvent evaporation method using different amounts of chitosan and purified by preparative size exclusion chromatography. The characterization by photon correlation spectroscopy and zeta potential measurements showed a small increase in size and an increase of zeta potential with increasing amounts of chitosan. Binding efficiency and complex stability with 2OMR was high in water and correlated well with the chitosan content of particles but was weak in physiologically relevant media (PBS and RPMI cell culture medium). However, flow cytometry analysis showed that the uptake of 2OMR into A549 lung cancer cells was considerably higher in combination with nanoparticles and dependent on the amount of chitosan when compared to 2OMR alone. Confocal laser scanning microscopy revealed that the uptake into A549 cells is mediated via complexes of 2OMR and chitosan/PLGA nanoparticles despite the weak binding in cell culture medium. The nanoparticles were well tolerated and efficient in inhibiting telomerase activity.

Decomposition of the telomere-targeting agent BRACO19 in physiological media results in products with decreased inhibitory potential.

The stability of the acridine-based telomere-targeting agent BRACO19, a G-quadruplex stabilizing substance, was tested at different pH, temperature and in different dissolution media. Analysis was performed by HPLC. Decomposition products were examined by LC/MS and NMR. The TRAP assay was used to determine the inhibitory potential of the decomposition products on telomerase activity. The results show that the stability of BRACO19 strongly depends on pH and temperature. Decomposition was fastest at physiological pH and temperature while the type of dissolution medium had no major influence on stability. The most probable mechanism for this decomposition seems to be a hydrolysis of the amide bonds in position 3 and 6 of the acridine ring and/or a deamination of the phenyl ring. The decomposition products showed a reduced inhibitory potential compared to the parent compound BRACO19. The results demonstrate that the preparation of dosage forms and their storage conditions will have an important influence on the stability--and hence biological efficacy--of BRACO19 and related substances.

Influence of human skin specimens consisting of different skin layers on the result of in vitro permeation experiments.

The literature exhibits high variation in results from drug permeation experiments across human skin. Our purpose was to investigate the influence of human skin specimens, consisting of different skin layers and resulting from different skin preparation techniques, on the in vitro permeation of a model drug, i.e. flufenamic acid (FFA). FFA permeation across human (1) trypsin-isolated stratum corneum, (2) heat-separated epidermis and (3) dermis, (4) dermatomized skin and (5) full-thickness skin (FTS) from either a hydrophilic or lipophilic donor was investigated in Franz-type diffusion cells. Cumulative permeated drug amounts were plotted versus time, and a fit to Fick's 2nd law of diffusion was performed. Since performing skin diffusion experiments in the laboratory is time consuming and expensive, especially when using FTS, we also investigated the possibility of calculating the resistances of composite skin layers from the diffusion resistances of the individual skin layers. Due to short lag time, practical handling and economic preparation, heat-separated epidermis appears to be superior in human skin in vitro permeation experiments compared to separated stratumcorneum sheets, dermatomized skin and FTS. Furthermore, we found a good correlation between calculated and experimental resistances which underlines that calculation of the total diffusion resistance of composed skin preparations from resistances of individual skin layers is legitimate and useful. Considering our findings, improved interpretation of literature data and more consistent results for future permeation experiments are possible.

Incidence and outcome of traumatic brain injury in an urban area in Western Europe over 10 years.

INTRODUCTION: Valid epidemiological data on incidence and outcome of traumatic brain injury (TBI) show great variability. A study on incidence, severity and outcome of TBI was conducted in an urban area of one million inhabitants. MATERIALS AND METHODS: 130,000 prehospital emergencies were screened for TBI. INCLUSION CRITERIA: Glasgow Coma Scale (GCS) score or=2 with confirmed TBI via appropriate diagnostics. RESULTS: Annual incidence was 7.3/100,000. Overall mortality rate was 45.8%: 182 (28%) were prehospital deaths, 116 (17.8%) patients died in hospital. Two hundred and fourteen of 352 (60.8%) surviving patients were sufficiently rehabilitated at discharge [Glasgow Outcome Scale (GOS) score = 1], but 138 patients (39.2%) survived with persisting deficits. GOS was associated with initial GCS and AIS(head). CONCLUSION: The incidence of TBI was lower compared to the literature. The overall mortality was high, especially prehospital and early in-hospital mortality rates.

Dexamethasone-loaded nanoparticle-coated microparticles: correlation between in vitro drug release and drug transport across Caco-2 cell monolayers.

This work reports the preparation of dexamethasone in nanoparticle-coated microparticles and the study of the influence of such microencapsulation on drug absorption across Caco-2 cell monolayers. Nanoparticle-coated microparticles were prepared by spray-drying using nanocapsules (NC) or nanospheres (NS) in aqueous suspensions as coating material. Drug contents ranged from 64 to 134mgg(-1), yields between 49% and 67% and moisture content below 2.0%. SEM and AFM analysis demonstrated that the nanoparticle-coated microparticles (20-53microm) show nanostructures on their surface with a similar diameter compared to the aqueous suspensions. The type of nanocoating material had a significant influence on the drug release profile and on the drug permeation across Caco-2 cells: NC-coated microparticles led to a prolonged release and slower transport across Caco-2 cell monolayers, while the NS-coated microparticles showed a faster release and Caco-2 transport compared to uncoated microparticles. The correlation between the amount of drug permeated and the drug released (%) suggests that the drug absorption from such a delivery system is controlled mainly by the release rate rather than by epithelial permeability. Caco-2 transport studies appear to be a useful characterization tool for the development of microparticulate oral controlled release systems.

Intracoronary enalaprilat during angioplasty for acute myocardial infarction: alleviation of postischaemic neurohumoral and inflammatory stress?

AIM: Reperfusion after myocardial ischaemia is associated with a distinct ischaemia/reperfusion injury. Since ACE-inhibition, beyond its influence on cardiac angiotensin II formation and kinin metabolism, has been shown to be cardioprotective by decreasing leucocyte adhesion and endothelin-1 (ET-1) release, we investigated the effects of intracoronary (i.c.) enalaprilat during primary angioplasty in acute myocardial infarction. METHODS AND RESULTS: Twenty-two patients were randomized to receive i.c. enalaprilat (50 micro g) or placebo immediately after reopening of the infarct-related artery (IRA). Plasma concentrations of soluble L-selectin, P-selectin, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), ET-1 and nitric oxide metabolite concentrations (NOx) were measured in pulmonary arterial blood. Coronary blood flow was assessed using corrected thrombolysis in myocardial infarction (TIMI) frame counts (CTFC). During reperfusion, there was a significant increase in sL-selectin, sP-selectin and ET-1 in the placebo group, which was greatly diminished by enalaprilat. Levels of sVCAM-1 and sICAM-1 were not affected in either group. CTFC in the placebo group remained higher than normal in both the IRA and nonculprit vessels, whereas myocardial blood flow improved with enalaprilat. CONCLUSION: Enalaprilat as adjunct to primary angioplasty might be a protective approach to prevent leucocyte adhesion and the release of ET-1, thereby improving coronary blood flow.

Influence of nanoencapsulation on human skin transport of flufenamic acid.

The effect of the inclusion of flufenamic acid in poly(lactide-co-glycolide) nanoparticles on the transport of flufenamic acid into excised human skin was investigated. Penetration and permeation data were acquired using two different in vitro test systems: the Saarbrucken penetration model, where the skin acts as its own receptor medium, and the Franz diffusion cell, where the receptor medium is a buffer solution. For the stratum corneum, no differences were found between nanoencapsulated and free drug. Drug accumulation in the deeper skin layers and drug transport across human epidermis were slightly delayed for the nanoencapsulated drug compared to the free drug after shorter incubation times (<12 h). In contrast, after longer incubation times (>12 h), the nanoencapsulated drug showed a statistically significantly enhanced transport and accumulation (p < 0.05). Additionally, nanoencapsulated flufenamic acid was visualized by multiphoton fluorescence microscopy. Particles were found homogeneously distributed on the skin surface and within the dermatoglyphs, but no nanoparticles were detected within or between the corneocytes.

Hair follicles - a long-term reservoir for drug delivery.

Nanoparticles represent an important drug carrier system. Recently, we have reported on the penetration and storage behavior of particular and non-particular substances revealing the superiority of particular substances in the range of 300-400 nm. In this regard, it was assumed that the rigid hair shaft acts as a geared pump, moving the particles deeper into the hair follicle. In the present investigation, the storage reservoir capacity of the stratum corneum and the hair follicle infundibulum and canal are compared. Interestingly, we could demonstrate a 10 times longer storage within the hair follicles. These results underscore the importance of the hair follicle for drug delivery purposes, mainly highlighting new possibilities for the future concerning retarded delivery, application frequency, and galenic design.