Transdermal Therapeutic Systems (TTS) improve patient compliance especially due to its simple application and long-term action with the need to exchange the system every 12 hours to several days. The advantages also include elimination of first-pass effect, avoidance of gastrointestinal adverse effects, stable drug levels in the blood and simple discontinuation of therapy by patch removing. However, most drugs do not have the appropriate physicochemical properties to achieve therapeutic levels by transdermal application, therefore only a limited amount of drugs administered by this route is available on the market. Microneedles (MI) by their painless application appear to increase drug permeation when applied transdermally. In this review work, various types of MI (solid, coated, hollow, matrix, hydrogel forming) their size, shape, grouping, but also materials and technologies used in MI production are described. Finally, the work is focused on current clinical trials in which MI have been tested. MI with their unique properties have potential to increase the range of transdermally administered drugs currently applied by another route of administration. MI can simply pave the way for transdermal delivery to poorly penetrating small molecules as well as large molecules such as vaccines, monoclonal antibodies, or siRNA.

• Klíčová slova
• clinical trials, materials, microneedles, shape, transdermal drug delivery, vaccine delivery,
• MeSH
• aplikace kožní MeSH
• jehly * MeSH
• léčivé přípravky aplikace a dávkování   MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• léčivé přípravky MeSH

The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.

• Klíčová slova
• 3D printing, Dermal delivery, Imiquimod, Microneedles, Nanocrystals,
• MeSH
• 3D tisk * MeSH
• aplikace kožní MeSH
• imichimod * chemie   aplikace a dávkování   MeSH
• jehly * MeSH
• kožní absorpce MeSH
• kůže metabolismus   MeSH
• lékové transportní systémy přístrojové vybavení   MeSH
• mikroinjekce přístrojové vybavení   MeSH
• nanočástice * chemie   aplikace a dávkování   MeSH
• polyethylenglykoly chemie   aplikace a dávkování   MeSH
• povidon chemie   MeSH
• rozpustnost * MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imichimod * MeSH
• poly(ethylene glycol)diacrylate MeSH Prohlížeč
• polyethylenglykoly MeSH
• povidon MeSH

Supramolecular self-assembly of a highly flexible and achiral meso bis(boron dipyrromethene) [bis(BODIPY)] dye straightforwardly yields fluorescent microfibers, exhibiting an intriguing anisotropic photonic behavior. This performance includes the generation of chiroptical activity owing to spontaneous mirror symmetry breaking (SMSB). Repetition of several self-assembly experiments demonstrates that the involved SMSB is not stochastic but quasi deterministic in the direction of the induced chiral asymmetry. The origin of these intriguing (chiro)photonic properties is revealed by fluorescent microspectroscopy studies of individual micrometric objects, combined with X-ray diffraction elucidation of microcrystals. Such a study demonstrates that J-like excitonic coupling between bis(BODIPY) units plays a fundamental role in their supramolecular organization, leading to axial chirality. Interestingly, the photonic behavior of the obtained fibers is ruled by inherent nonradiative pathways from the involved push-pull chromophores, and mainly by the complex excitonic interactions induced by their anisotropic supramolecular organization.

• Publikační typ
• časopisecké články MeSH

Enterotoxigenic Escherichia coli (ETEC) infections have been identified as a major cause of acute diarrhoea in children in developing countries, associated with substantial morbidity and mortality rates. Additionally, ETEC remains the most common cause of acute diarrhea of international travellers to endemic areas. The heat-labile toxin (LT) is a major virulence factor of ETEC, with a significant correlation between the presence of antibodies against LT and protection in infected patients. In the present work, we constructed a recombinant LTB unit (rLTB) and studied the capacity of this toxoid incorporated in microneedles (rLTB-MN) to induce a specific immune response in mice. MN were prepared from aqueous blends of the polymer Gantrez AN® [poly (methyl vinyl ether-co-maleic anhydride)], which is not cytotoxic and has been shown to possess immunoadjuvant properties. The mechanical and dissolution properties of rLTB-MNs were evaluated in an in vitro Parafilm M® model and in mice and pig skin ex vivo models. The needle insertion ranged between 378 µm and 504 µm in Parafilm layers, and MNs fully dissolved within 15 min of application inside porcine skin. Moreover, female and male BALB/c mice were immunized through ear skin with one single dose of 5 μg·rLTB in MNs, eliciting significant fecal anti-LT IgA antibodies, higher in female than in male mice. Moreover, we observed an enhanced production of IL-17A by spleen cells in the immunized female mice, indicating a mucosal non-inflammatory and neutralizing mediated response. Further experiments will now be required to validate the protective capacity of this new rLTB-MN formulation against this deadly non-vaccine-preventable disease.

• Klíčová slova
• LTB subunit, dissolving microneedles, enterotoxigenic Escherichia coli (ETEC), intradermal vaccine,
• Publikační typ
• časopisecké články MeSH

Electrical characteristics of living cells have been proven to reveal important details about their internal structure, charge distribution and composition changes in the cell membrane, as well as the extracellular context. An impedance flow cytometry is a common approach to determine the electrical properties of a cell, having the advantage of label-free and high throughput. However, the current techniques are complex and costly for the fabrication process. For that reason, we introduce an integrated dual microneedle-microchannel for single-cell detection and electrical properties extraction. The dual microneedles utilized a commercially available tungsten needle coated with parylene. When a single cell flows through the parallel-facing electrode configuration of the dual microneedle, the electrical impedance at multiple frequencies is measured. The impedance measurement demonstrated the differential of normal red blood cells (RBCs) with three different sizes of microbeads at low and high frequencies, 100 kHz and 2 MHz, respectively. An electrical equivalent circuit model (ECM) was used to determine the unique membrane capacitance of individual cells. The proposed technique demonstrated that the specific membrane capacitance of an RBC is 9.42 mF/m-2, with the regression coefficients, ρ at 0.9895. As a result, this device may potentially be used in developing countries for low-cost single-cell screening and detection.

• Klíčová slova
• Single-cell analysis, impedance analysis, impedance flow cytometry, microfluidic,
• MeSH
• analýza jednotlivých buněk MeSH
• buněčná membrána fyziologie   MeSH
• elektrická impedance * MeSH
• elektrická kapacitance MeSH
• erytrocyty * fyziologie   MeSH
• lidé MeSH
• průtoková cytometrie * přístrojové vybavení   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Microneedling (percutaneous collagen induction therapy) is a new promising miniinvasive therapeutic method for the treatment of skin alterations of different aetiology, including burn scars. Since 2016, it is also available at our department. The microtraumatization of scars with the Dermaroller® leads to an activation of the healing cascade, activation of growth factors, which activate cell proliferation in the wound, increased synthesis and deposit of collagen - elastin complex with successive transformation of collagen III to collagen I, to neoangiogenesis and thus to accelerated scar remodelling. MATERIAL AND METHODS: In the pilot study conducted in 2016, the microneedling method with Dermaroller® with 2.5 mm needles was used in six patients (two males, four females; age 25-73 years) with stabilized scars after previous application of split thickness skin graft due to thermal injury. We repeated the microneedling procedure in three intervals approximately 6 to 8 weeks apart, with the use of topical anaesthesia. RESULTS: Preliminary results showed a subjective improvement of the scars. Objective evaluation with the Vancouver Scar Score showed an improvement of an average of two points before and after treatment. CONCLUSION: Our first clinical experience show that microneedling appears to be a suitable microinvasive method for the improvement of scar quality after burn trauma.

• Klíčová slova
• Dermaroller®, Microneedling, collagen induction therapy burn scar.,
• MeSH
• butyrofenony MeSH
• jehly * MeSH
• jizva * terapie   MeSH
• kolagen * terapeutické užití   MeSH
• kůže MeSH
• lidé MeSH
• pilotní projekty MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• butyrofenony MeSH
• kolagen * MeSH
• metylperon MeSH Prohlížeč

BACKGROUND: There is a continuing interest in finding effective methods for scar treatment. Dry needling is gaining popularity in physiotherapy and is defined by Western medicine as a type of acupuncture. The terms acupuncture and dry needling have been used interchangeably so we have focused on the efficacy of dry needling or acupuncture in scar treatment. OBJECTIVE: The aim of this systematic review was to determine the usefulness of dry needling or local acupuncture for scar treatment. In our search process, we used the terms 'acupuncture,' 'needling,' or 'dry needling' to identify all relevant scientific papers. We have focused on the practical aspects of local management of different scar types with dry needling or acupuncture. SEARCH STRATEGY: The search strategy included different combinations of the following keywords: 'scar', 'keloid', 'dry needling', 'needling', 'acupuncture', 'treatment', 'physical therapy'. This systematic review was conducted in accordance with PRISMA guidelines. MEDLINE (PubMed, EBSCOHost and Ovid), EMBASE (Elsevier), and Web of Science databases were searched for relevant publications from inception through October 2023. INCLUSION CRITERIA: The studies that investigated the effectiveness of dry needling or acupuncture for scar treatment were included. DATA EXTRACTION AND ANALYSIS: The main extraction data items were: the needling technique; needle: diameter, length; needling locations; manual needling manipulation; number of sessions; settings; outcomes and results. RESULTS: As a result of a comprehensive search, 11 manuscripts were included in the systematic review, of which eight were case reports, two were randomized trials and one study concerned case series. Two case reports scored 2-4 out of 8 points on the JBI checklist, five studies scored 5-7, and one study scored 8 points. The methodological quality of the two clinical trials was rated as good or fair on the PEDro scale. The case series study scored 7 of 10 points on the JBI checklist. A meta-analysis was not possible as only two randomized trials, eight case reports, and one case series were eligible for review; also, scar assessment scales and pain severity scales were highly heterogeneous. CONCLUSIONS: The studies differed regarding the delivery of dry needling or local acupuncture for scar treatment. Differences included treatment frequency, duration, number of treatments, selection of needle insertion sites, number of needles used, angle of needle placement, and use of manual needling manipulation. SYSTEMATIC REVIEW REGISTRATION: INPLASY no. 202310058.

• Klíčová slova
• Acupuncture, Dry needling, Scar, Treatment,
• MeSH
• akupunkturní terapie * metody   MeSH
• jizva MeSH
• kazuistiky jako téma MeSH
• lidé MeSH
• perkutánní indukce kolagenu MeSH
• techniky fyzikální terapie MeSH
• terapie suchou jehlou * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

Hyaluronan (HA) plays a fundamental role in maintaining the homeostasis on skin health. Furthermore, the effect of HA in skin inflammatory diseases is worth studying in the next future. HA and its conjugates change the solubility of active pharmaceutical ingredients, improve emulsion properties, prolong stability, reduce immunogenicity, and provide targeting. HA penetrates to deeper layers of the skin via several mechanisms, which depend on the macromolecular structure and composition of the formulation. The cellular and molecular mechanisms involved in epidermal dysfunction and skin aging are not well understood. Nevertheless, HA is known to selectively activate CD44-mediated keratinocyte signaling that regulates its proliferation, migration, and differentiation. The molecular size of HA is critical for molecular mechanisms and interactions with receptors. High molecular weight HA is used in emulsions and low molecular weight is used to form nanostructured lipid carriers, polymeric micelles, bioconjugates, and nanoparticles. In the fabrication of microneedles, HA is combined with other polymers to enhance mechanical properties for piercing the skin. Hence, this review aims to provide an overview of the current state of the art and last reported ways of processing, and applications in skin drug delivery, which will advocate for their broadened use in the future.

• Klíčová slova
• amphiphiles, hyaluronan, self-assembly, skin penetration, stratum corneum,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

One of the ways to increase a low rate of vaccination against the flu in the Czech population is using new vaccination methods, e.g. the intradermal flu vaccine application method. This method uses a high skin immune potential, where a great amount of dendritic cells, macrophages, lymphocytes as well as abundant capillary and lymphatic supply can be found. A progressive microneedle application system allows the accurate application right into the dermis and a dosage consistency without any necessity of much experience and training in intradermal administration. Comparable results of immunogenity with lower antigen content and less vaccine amount are reached with intramuscular application in adults up to 59. Using the same antigen amount as in intramuscular application in people older than 60, significantly better results are reached. A new intradermal vaccine IDflu is registered in Europe for people from the age of 18 and it is considered to be a new alternative way to raise popularity of flu vaccination in lay and professional public. The microneedle intradermal application system brings an easier way of vaccination for doctors with application of less amount of vaccine and there is no need to remove air from the syringe and no need of aspiration. The vaccine will be introduced in the Czech market before the flu season 2010/2011.

• MeSH
• injekce intradermální přístrojové vybavení   metody   MeSH
• lidé MeSH
• vakcíny proti chřipce aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• vakcíny proti chřipce MeSH