The Contest of Nanoparticles: Searching for the Most Effective Topical Delivery of Corticosteroids.

Owing to their complicated pathophysiology, the treatment of skin diseases necessitates a complex approach. Conventional treatment using topical corticosteroids often results in low effectiveness and the incidence of local or even systemic side effects. Nanoformulation of potent anti-inflammatory drugs has been selected as an optimal strategy for enhanced topical delivery of corticosteroids. In order to assess the efficiency of various nanoformulations, we formulated hydrocortisone (HC) and hydrocortisone-17-butyrate (HCB) into three different systems: lipid nanocapsules (LNC), polymeric nanoparticles (PNP), and ethosomes (ETZ). The systems were characterized using dynamic light scattering for their particle size and uniformity and the morphology of nanoparticles was observed by transmission electron microscopy. The nanosystems were tested using ex vivo full thickness porcine and human skin for the delivery of HC and HCB. The skin penetration was observed by confocal microscopy of fluorescently labelled nanosystems. ETZ were proposed as the most effective delivery system for both transdermal and dermal drug targeting but were also found to have a profound effect on the skin barrier with limited restoration. LNC and PNP were found to have significant effects in the dermal delivery of the actives with only minimal transdermal penetration, especially in case of HCB administration.

Polymorphism, Nanostructures, and Barrier Properties of Ceramide-Based Lipid Films.

Ceramides belong to sphingolipids, an important group of cellular and extracellular lipids. Their physiological functions range from cell signaling to participation in the formation of barriers against water evaporation. In the skin, they are essential for the permeability barrier, together with free fatty acids and cholesterol. We examined the periodical structure and permeability of lipid films composed of ceramides (Cer; namely, N-lignoceroyl 6-hydroxysphingosine, CerNH24, and N-lignoceroyl sphingosine, CerNS24), lignoceric acid (LIG; 24:0), and cholesterol (Chol). X-ray diffraction experiments showed that the CerNH24-based samples form either a short lamellar phase (SLP, d ∼ 5.4 nm) or a medium lamellar phase (MLP, d = 10.63-10.78 nm) depending on the annealing conditions. The proposed molecular arrangement of the MLP based on extended Cer molecules also agreed with the relative neutron scattering length density profiles obtained from the neutron diffraction data. The presence of MLP increased the lipid film permeability to the lipophilic model permeant (indomethacin) relative to the CerNS24-based control samples and the samples that had the same lipid composition but formed an SLP. Thus, the arrangement of lipids in various nanostructures is responsive to external conditions during sample preparation. This polymorphic behavior directly affects the barrier properties, which could also be (patho)physiologically relevant.

The Effect of Menstrual Cycle on Perceptual Responses in Athletes: A Systematic Review With Meta-Analysis.

This article aimed to investigate the effects of menstrual cycle phases on perceptual responses in athletes by means of systematic review and meta-analysis. The search was conducted in the PubMed, Web of Science, and Sport Discus databases considering articles with two or more menstrual phases for comparison. The PECO criteria were used for the keywords "menstrual cycle," "athletes," and "perceptual responses" with their respective entry terms. Of 1.165 records identified, 14 articles were available for the final evaluation, while eight articles were eligible for a meta-analysis. The perceptual responses evaluated in the studies were: motivation, competitiveness, sleep quality, stress, muscle soreness, fatigue, perceived effort, mood, menstrual symptoms, perceived endurance, and readiness. The meta-analysis was conducted for perceived effort only. The results showed that the level of perceived exertion does not differ two phases of the menstrual cycle (MD = 3.03, Q = 1.58, df = 1, p = 0.209), whereas RPE was 19.81 ± 0.05 and 16.27 ± 0.53 at day 1-5 and day 19-24, respectively. Two studies found statistically significant changes in motivation and competitiveness during the cycle, with better outcomes in ovulatory phase compared to follicular and luteal. One study found an increase in mood disturbance in the pre-menstrual phase (vs. mid-cycle); one decreased vigor in the menstrual phase (vs. luteal); one increased the menstrual symptoms in the follicular phase (vs. ovulation), and one study reported increased fatigue and decreased sleep quality on luteal phase (vs. follicular). The remaining studies and variables were not affected by the menstrual cycle phase. Based on the results from the studies selected, some perceptual responses are affected in different menstrual cycle phases. A "favorable" subjective response in athletes was noticed when the ovarian hormones present an increase in concentration levels compared to phases with lower concentration. Different perceptual variables and methodological approaches limit the generalization of the conclusion.

N-Alkylmorpholines: Potent Dermal and Transdermal Skin Permeation Enhancers.

Transdermal drug delivery is an attractive non-invasive method offering numerous advantages over the conventional routes of administration. The main obstacle to drug transport is, however, the powerful skin barrier that needs to be modulated, for example, by transdermal permeation enhancers. Unfortunately, there are still only a few enhancers showing optimum properties including low toxicity and reversibility of enhancing effects. For this reason, we investigated a series of new N-alkylmorpholines with various side chains as potential enhancers in an in vitro permeation study, using three model permeants (theophylline, indomethacin, diclofenac). Moreover, electrical impedance, transepidermal water loss, cellular toxicity and infrared spectroscopy measurements were applied to assess the effect of enhancers on skin integrity, reversibility, toxicity and enhancers' mode of action, respectively. Our results showed a bell-shaped relationship between the enhancing activity and the hydrocarbon chain length of the N-alkylmorpholines, with the most efficient derivatives having 10-14 carbons for both transdermal and dermal delivery. These structures were even more potent than the unsaturated oleyl derivative. The best results were obtained for indomethacin, where particularly the C10-14 derivatives showed significantly stronger effects than the traditional enhancer Azone. Further experiments revealed reversibility in the enhancing effect, acceptable toxicity and a mode of action based predominantly on interactions with stratum corneum lipids.