Clinical Studies Using Topical Melatonin.

Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to its widespread oral use as a dietary supplement to improve sleep. A far smaller number of articles describe the clinical applications of topical melatonin to treat or prevent skin disorders by exploiting its antioxidant and anti-inflammatory activities. This review focuses on the clinical studies in which melatonin was applied on the skin as a photoprotective, anti-aging, or hair growth-promoting agent. The methodologies and results of such studies are discussed to provide an overall picture of the state of the art in this intriguing field of research. The clinical studies in which melatonin was applied on the skin before exposure to radiation (UV, sunlight, and high-energy beams) were all characterized by an appropriate design (randomized, double-blind, and placebo-controlled) and strongly support its clinical efficacy in preventing or reducing skin damage such as dermatitis, erythema, and sunburn. Most of the studies examined in this review do not provide a clear demonstration of the efficacy of topical melatonin as a skin anti-aging or as a hair growth-promoting agent owing to limitations in their design and/or to the use of melatonin combined with extra active ingredients, except for one trial that suggests a possible beneficial role of melatonin in treating some forms of alopecia in women. Further research efforts are required to reach definitive conclusions concerning the actual benefits of topical melatonin to counteract skin aging and hair loss.

Development and Evaluation of Tacrolimus Loaded Nano-Transferosomes for Skin Targeting and Dermatitis Treatment.

Tacrolimus (TRL) is used for the treatment of atopic dermatitis (AD) due to its T-cell stimulation effect. However, its significantly poor water solubility, low penetration and cytotoxicity have reduced its topical applications. Herein, tacrolimus loaded nano transfersomes (TRL-NTs) were prepared, followed by their incorporation into chitosan gel to prepare tacrolimus loaded nano transfersomal gel (TRL-NTsG). TEM analysis of the TRL-NTs was performed to check their morphology. DSC, XRD and FTIR analysis of the TRL-NTs were executed after lyophilization. Similarly, rheology, spreadability and deformability of the TRL-NTsG were investigated. In vitro release, ex vivo permeation and in vitro interaction of TRL-NTsG with keratinocytes and fibroblasts as well as their co-cultures were investigated along with their in vitro cell viability analysis. Moreover, in vivo skin deposition, ear thickness, histopathology and IgE level were also determined. Besides, 6 months stability study was also performed. Results demonstrated the uniformly distributed negatively charged nanovesicles with a mean particle size distribution of 163 nm and zeta potential of -27 mV. DSC and XRD exhibited the thermal stability and amorphous form of the drug, respectively. The TRL-NTsG showed excellent deformability, spreadability and rheological behavior. In vitro release studies exhibited an 8-fold better release of TRL from the TRL-NTsG. Similarly, 6-fold better permeation and stability of the TRL-NTsG with keratinocytes and fibroblasts as well as their co-cultures was observed. Furthermore, the ear thickness (0.6 mm) of the TRL-NTsG was found significantly reduced when compared with the untreated (1.7 mm) and TRL conventional gel treated mice (1.3 mm). The H&E staining showed no toxicity of the TRL-NTsG with significantly reduced IgE levels (120 ng/mL). The formulation was found stable for at least 6 months. These results suggested the efficacy of TRL in AD-induced animal models most importantly when incorporated in NTsG.

Antimicrobial peptides for bone tissue engineering: Diversity, effects and applications.

Bone tissue engineering has been becoming a promising strategy for surgical bone repair, but the risk of infection during trauma repair remains a problematic health concern worldwide, especially for fracture and infection-caused bone defects. Conventional antibiotics fail to effectively prevent or treat bone infections during bone defect repair because of drug-resistance and recurrence, so novel antibacterial agents with limited resistance are highly needed for bone tissue engineering. Antimicrobial peptides (AMPs) characterized by cationic, hydrophobic and amphipathic properties show great promise to be used as next-generation antibiotics which rarely induce resistance and show potent antibacterial efficacy. In this review, four common structures of AMPs (helix-based, sheet-based, coil-based and composite) and related modifications are presented to identify AMPs and design novel analogs. Then, potential effects of AMPs for bone infection during bone repair are explored, including bactericidal activity, anti-biofilm, immunomodulation and regenerative properties. Moreover, we present distinctive applications of AMPs for topical bone repair, which can be either used by delivery system (surface immobilization, nanoparticles and hydrogels) or used in gene therapy. Finally, future prospects and ongoing challenges are discussed.

Skin-Permeable Nano-Lithocholic Lipidoid Efficiently Alleviates Psoriasis-like Chronic Skin Inflammations.

Long-term application of topical therapeutics for psoriasis has a plethora of side effects. Additionally, skin-permeating agents used in their formulations for deeper dermal delivery damage the skin. To address these limitations, we developed novel lithocholic acid analogues that could form lipid nanoparticles (nano-LCs) spontaneously in the aqueous milieu, permeate through the skin, penetrate the deeper dermal layers, and exert anti-inflammatory effects against psoriasis-like chronic skin inflammations. Prior findings demonstrated that lithocholic acid acts as a vitamin D receptor agonist without affecting the Ca+2 metabolism and also as an antagonist for ephrin type-A receptor 2 (EphA2). Taking cues from the previous findings, lithocholic acid derivatives with twin alkyl chains (LC6, LC8, LC10, and LC-12) were synthesized, nanoparticles (nano-LCs) were prepared, and they were evaluated for their skin permeability and anti-inflammatory properties. Among these nano-LCs, nano-LC10 demonstrated superior anti-inflammatory properties and inhibition of keratinocyte proliferation in various cell-based evaluations. Furthermore, the therapeutic efficiency of nano-LC10 was evaluated in an imiquimod-induced psoriasis-like mouse model and demonstrated comparable efficiency with the standard topical formulation, Sorvate, in reducing skin inflammations. Nano-LC10 also reduced systemic inflammation, organ toxicity, and also proinflammatory serum cytokine levels. Overall, nano-lithocholic lipidoid (nano-LC10) can be a potential novel class of therapeutics for topical application in treating psoriasis.

Therapeutic Application of Microsponges-based Drug Delivery Systems.

Microsponges delivery systems (MDS) are highly porous, cross-linked polymeric systems that activate due to temperature, pH, or when rubbed. MDS offer a wide range of advantages, like controlled drug release, site-specific action, stability over a broad range of pH, less irritation, cost-effectiveness, and improved patient compliance. They can be transformed into various dosage forms like creams, gels, and lotions. MDS are suitable for the treatment of topical disorders like acne, psoriasis, dandruff, eczema, scleroderma, hair loss, skin cancer, and other dreadful diseases. The applications of MDS in drug delivery are not limited to topical drug delivery but are also explored for oral, parenteral, and pulmonary drug deliveries. Microsponges have been studied for colon targeting of drugs and genes. Additionally, MDS have several applications such as sunscreen, cosmetics, and over-the-counter (OTC) products. Furthermore, MDS do not actuate any irritation, genotoxicity, immunogenicity, or cytotoxicity. Therefore, this review extensively highlights microsponges, their advantages, key factors affecting their characteristics, their therapeutic applications in topical disorders and in cancer, their use as cosmetics, as well as recent advances in MDS and the associated challenges.

Development and Characterization of a Hydrogel Containing Silver Sulfadiazine for Antimicrobial Topical Applications. Part II: Stability, Cytotoxicity and Silver Release Patterns

Abstract Hydrogels are interesting for use in the treatment of topical wounds due to their virtually zero toxicity, and capacity for extended release of pharmaceuticals. Silver sulfadiazine (SSDZ) is the drug of choice in the treatment of skin burns. The aim of the study was to determine cytotoxicity, antimicrobial activity and stability of a PVA hydrogel with integrated silver sulfadiazine. SSDZ-hydrogels were prepared using 10% (w/w) PVA (either 89% or 99% hydrolyzed) and 1% (w/w) silver sulfadiazine. Cellular viability was assessed via MTS assays, antimicrobial activity via disk-diffusion and accelerated stability tests were carried out with analysis at 0, 30, 60, 90 and 180 days of storage at 40 ± 2 °C and a relative humidity of 75 ± 5%. The parameters evaluated included organoleptic characteristics, moisture, swelling ability, mechanical strength, FTIR, XRD, TGA and DSC, and silver release patterns via XRD and potentiometry. Cell viability tests indicated some cytotoxicity, although within acceptable levels. After 90 days of storage, SSDZ hydrogel samples exhibited a brown coloration, probably due to the formation of Ag or Ag2O nanoparticles. The SSDZ-loaded hydrogels suffered visual and physical changes; however, these changes did not compromise its use as occlusive wound dressings or its antimicrobial properties.

[Dysbalance between the immune system and skin microbiome in chronic inflammatory dermatoses]. / Gestörtes Gleichgewicht von Immunsystem und Hautmikrobiom bei chronisch entzündlichen Dermatosen.

BACKGROUND: The skin is an organ frequently affected by chronic diseases. Inflammatory, immune-mediated dermatoses such as atopic dermatitis and psoriasis show a high prevalence as well as a significant impact on the quality of life of those affected. In a large proportion of cases, atopic dermatitis is associated with a marked change in microbial colonization of both clinically healthy and affected skin. In psoriasis, changes to this effect have been described, but clinical relevance remains elusive. AIM: In recent years, increasing knowledge has been gained in microbiome research with resulting clinical relevance. The present article deals with the disturbed balance of the immune system and the skin microbiome in chronic inflammatory dermatoses on the basis of atopic dermatitis and psoriasis vulgaris. MATERIALS AND METHODS: A literature search was performed in PubMed and Medline databases (entries until 09 April 2021). RESULTS: Staphylococcus aureus is known to play a central pathophysiological role in atopic dermatitis. This is revisited in light of new insights regarding biodiversity and immunoregulatory processes. In psoriasis, a more heterogeneous body of data emerges regarding the microbiome and its contribution to disease development. DISCUSSION: While topical applications to directly influence the microbiome are already being tested in atopic dermatitis, further knowledge regarding the pathophysiological significance of the microbiota is still needed in psoriasis.

Usnic Acid: Potential Role in Management of Wound Infections.

Usnic acid (UA) is a secondary lichen metabolite extensively studied for the broad variety of biological features. The most interesting property of UA is its antimicrobial activity against Gram-positive bacteria growing either in planktonic or in biofilm mode. In this chapter, the most relevant studies assessing usnic acid activity against microbial biofilms have been summarized and the potential role of UA in the management of biofilm-based wound infections has been critically discussed. Additionally, an overview of the main strategies adopted so far to reduce drug toxicity and increase bioavailability is given in the perspective of a safe use of UA in the clinical management of infected wounds.

Anti-inflammatory and antioxidant nanostructured cellulose membranes loaded with phenolic-based ionic liquids for cutaneous application.

The utilization of natural compounds, such as phenolic acids and biopolymers, in the healthcare domain is gaining increasing attention. In this study, bacterial nanocellulose (BC) membranes were loaded with ionic liquids (ILs) based on phenolic acids. These ionic compounds, with improved solubility and bioavailability, were prepared by combining the cholinium cation with anions derived from caffeic, ellagic and gallic acids. The obtained BC-ILs membranes were homogeneous, conformable and their swelling ability agreed with the solubility of each IL. These membranes revealed a controlled ILs dissolution rate in the wet state and high antioxidant activity. In vitro assays performed with Raw 264.7 macrophages and HaCaT keratinocytes revealed that these novel BC-ILs membranes are non-cytotoxic and present relevant anti-inflammatory properties. Diffusion studies with Hanson vertical diffusion cells showed a prolonged release profile of the ILs from the BC membranes. Thus, this work, successfully demonstrates the potential of BC-ILs membranes for skin treatment.

Layered Double Hydroxide-Based Functional Nanohybrids as Controlled Release Carriers of Pharmaceutically Active Ingredients.

The chemical stability, degradation and penetration ability of pharmaceutically active ingredients in topical formulations are the greatest challenges because of problems with the protection of actives for long times and with delivery. Therefore, the development of unique and efficient substrate material is vital for their protection and controlled drug release. Layered double hydroxides (LDHs) known as hydrotalcite like compounds possess positive charges due to isomorphic substitutions, which are counterbalanced by hydrated exchangeable anions located in the interlayer region. Some of the active ingredient molecules can be intercalated into the inner region of the LDHs through ionic bonding, hydrogen bonding or van der Waals interaction to form nanohybrids, which are more potent for their protection and controlled-release. This account focuses on our recent research efforts and key scientific and technical challenges in the development of LDH based nanohybrids for commercial use in advanced controlled release carriers of active ingredients in topical formulations.

Development and characterization of a hydrogel containing silver sulfadiazine for antimicrobial topical applications.

Development and optimization of a hydrogel with impregnated silver sulfadiazine was pursued, for antimicrobial topical applications. The selected hydrogel exhibited a homogeneous appearance, with whitish colloration and devoid of any fractures or cracks. The content in impregnated silver sulfadiazine was within established limits (1%, w/w) with a standard deviation of up to 1.28%. The hydrogel presented a good characteristic in relation to release of the active antimicrobial principle, verified through swelling tests and antimicrobial activity. The swelling tests indicated a higher increase in weight during the first 6 h of contact with a moist environment, with a maximum value of 266.00 ± 0.81, and with maintenance of the original shape of the hydrogel. The impregnated silver sulfadiazine presented antimicrobial activity, as expected, indicating a prolonged release of the drug. The infrared spectra of the hydrogel with impregnated silver sulfadiazine indicated that the drug did not engage in any bonds with the polymeric matrix, which otherwise could have reduced its antimicrobial activity. The mechanical resistance tests produced good results, indicating that the hydrogels may be utilized in different locations of the human body with skin lesions.

Iontophoresis: principles and applications / Iontoforese: princípios e aplicações

Introduction Iontophoresis is a noninvasive technique used to increase transdermal penetration of substances through the skin layer (epidermis, dermis and hypodermis) in a controlled manner. Technological advance in recent decades have provided reduced cost of equipment needed for implementation, which allowed for the expansion of this technique. Objective The aim of this paper is to present the state of the art on iontophoresis, ranging from the atomic characteristics of the ion formation to the current applications of the technique. Methods Were researched papers from databases: IOP publishing, ScienceDirect, Pubmed, Springer, IEEE Xplore, Google Scholar and books with keywords iontophoresis, ions, topical applications between 1967 and 2010. Results Were selected (number of papers and database) 1 IOP Publishing, 1 from ScienceDirect, Central, 1 from Springer, 2 from PubMed, 11 from IEEE Xplore, 35 from Google Scholar, and 15 books, totaling 66 references and websites with nationally marketed electrotherapy products. Conclusion Iontophoresis is suitable for applications such as acetic acid (calcific tendinitis and myositis ossificans), calcium chloride and magnesium sulfate (control of musculoskeletal spasms), dexamethasone (inflammation), lidocaine (inflammation of soft tissues), zinc oxide (rheumatoid arthritis). It is also used in cosmetic applications with devices attached to the skin and for eye treatment aimed at specific tissues of the eye, providing a treatment option for various eye diseases, reducing the complications secondary to traditional methods of treatment. The advantages are the significant increase in the release and control of therapeutic agents, including drugs with high molecular weight. The disadvantages of iontophoresis are the complexity of the drug release system and prolonged exposure of the skin to an electrical current. .

Introdução A iontoforese é uma técnica não invasiva utilizada para aumentar, de forma controlada, a penetração transdermal de substâncias através das camadas da pele (epiderme, derme e hipoderme). O avanço tecnológico nas últimas décadas proporcionou uma redução no custo dos equipamentos necessários à sua aplicação, o que possibilitou a expansão dessa técnica. Objetivo Apresentar o estado da arte sobre iontoforese, abrangendo desde as características atômicas da formação do íon até as atuais aplicações da técnica. Métodos Foram pesquisados artigos das bases de pesquisa: IOP publishing, ScienceDirect, Pubmed, Springer, IEEE Xplore, Google Scholar e livros com os unitermos: iontophoresis, ions, topical applications entre os anos de 1967 e 2010. Resultados Foram selecionados (número de artigos e base de pesquisa) 1 da IOP Publishing, 1 da ScienceDirect, 1 da Springer, 2 da PubMed, 11 da IEEE Xplore, 35 do Google Scholar e 15 livros, totalizando 66 referências, além de websites com produtos comerciais nacionais de eletroterapia. Conclusão A iontoforese é indicada para aplicações como de ácido acético (tendinite calcificante e miosite ossificante), cloreto de cálcio e sulfato de magnésio (controle de espasmos musculoesqueléticos), dexametasona (inflamação), lidocaína (inflamação de tecidos moles), óxido de zinco (artrite reumatóide). Também é utilizada em aplicações cosméticas com dispositivos aderidos à pele e em tratamento ocular visando tecidos específicos do olho, oferecendo uma forma de tratamento para diversas doenças oculares, diminuindo as complicações apresentadas em métodos clássicos de tratamento. As vantagens ...

Bioactive polyphenols from muscadine grape and blackcurrant stably concentrated onto protein-rich matrices for topical applications.

OBJECTIVES: Natural botanical agents that are antimicrobial, or that modulate skin hyperpigmentation via tyrosinase inhibition, are increasingly sought in the cosmetic industry. METHODS: In this study, an efficient tactic is demonstrated for concentrating and stabilizing skin-beneficial bioactive compounds from muscadine grape and blackcurrant juice or muscadine pomace, into hemp flour (HF), hemp protein isolate (HPI) and soy protein isolate (SPI) matrices suitable for cosmetic applications. RESULTS: Anthocyanins were most efficiently captured from blackcurrant juice into HF (8.39 mg g(-1) ). HPI most effectively captured total phenolics from muscadine pomace (72.32 and 77.32 mg g(-1) from Noble and Carlos, respectively), while the three matrices incorporated highest levels of ellagic acid, gallic acid, and PAC B1 from Noble muscadine grape juice. The enriched matrices demonstrated effective in vitro inhibition of tyrosinase (up to 57.29% for blackcurrant juice-HPI matrix), and in general, juice sources provided greater inhibition on L-dopamine oxidation by tyrosinase than pomace sources. The polyphenol-enriched matrices effectively inhibited microbial proliferation in a screening assay against Staphylococcus aureus bacteria, whereas untreated HF, HPI or SPI did not inhibit bacterial growth. CONCLUSION: The technology of combining and stably concentrating phytoactive polyphenols with proteins has potential use for cosmetic topical applications.