In the present work biocompatible quercetin and curcumin nanovesicles were developed as a novel approach to prevent and restore skin tissue defects on chronic cutaneous pathologies. Stable and ...suitable quercetin- and curcumin-loaded phospholipid vesicles, namely liposomes and penetration enhancer-containing vesicles (PEVs), were prepared. Vesicles were made from a highly biocompatible mixture of phospholipids and alternatively a natural polyphenol, quercetin or curcumin. Liposomes were obtained by adding water, while PEVs by adding polyethylene glycol 400 and Oramix®CG110 to the water phase. Transmission electron microscopy, cryogenic-transmission electron microscopy and small- and wide-angle X-ray scattering showed that vesicles were spherical, oligo- or multilamellar and small in size (112–220nm). In vitro and in vivo tests underlined a good effectiveness of quercetin and curcumin nanovesicles in counteracting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induced lesions and inflammation. Myeloperoxydase activity, used to gauge inflammation, was markedly inhibited by quercetin liposomes (59%) and curcumin liposomes and polyethylene glycol (PEG)-PEVs (∼68%). Histology showed that PEG-PEVs provided an extensive re-epithelization of the TPA-damaged skin, with multiple layers of thick epidermis. In conclusion, nanoentrapped polyphenols prevented the formation of skin lesions abrogating the various biochemical processes that cause epithelial loss and skin damage.
Hair loss affects a large number of people worldwide and it has a negative impact on the quality of life. Despite the availability of different drugs for the treatment of hair disorders, therapeutic ...options are still limited and scarcely effective. An innovative strategy to improve the efficacy of alopecia treatment is presented in this work. Finasteride, the only oral synthetic drug approved by Unites States Federal Drug Administration, was loaded in phospholipid vesicles. In addition, baicalin was co-loaded as an adjuvant. Their effect on hair growth was evaluated in vitro and in vivo. Liposomes, hyalurosomes, glycerosomes and glycerol-hyalurosomes were manufactured by using a simple method that avoids the use of organic solvents. All the vesicles were small in size (∼100 nm), homogeneously dispersed (polydispersity index ≤0.27) and negatively charged (∼-16 mV). The formulations were able to stimulate the proliferation of human dermal papilla cells, which are widely used in hair physiology studies. The analysis of hair growth and hair follicles of C57BL/6 mice, treated with the formulations for 21 days, underlined the ability of the vesicles to improve hair growth by the simultaneous follicular delivery of finasteride and baicalin. Therefore, the developed nanosystems can represent a promising tool to ensure the efficacy of the local treatment of hair loss.
A pre-formulation study was carried out to obtain liposomal formulations of mometasone furoate as an alternative system to marketed forms of corticosteroid for the treatment of inflammatory skin ...lesions. Mometasone furoate was loaded in glycerosomes and glyceroethosomes, which were also modified with hyaluronic acid (glyceroethohyalurosomes). Vesicles were designed, elaborated, and characterized, and their biocompatibility, efficacy against oxidative stress and skin lesions were assessed in vitro, in human epidermal cells, and in vivo, in a mouse skin epidermal hyperplasia model. All formulations tested showed great encapsulation efficiency, nanometric size, formed monodispersed systems and a highly negative Z potential. Similar values were obtained over nine months storage at 4 °C, which indicates the great stability of the three types of nanoliposomes at least during the time tested. Among them, 0.1% mometasone furoate glyceroethohyalurosomes were the best formulation to protect cells against oxidative stress and their anti-inflammatory efficacy was confirmed in vivo, being even more effective than the marketed form (Elocom
), as the reduction in the inflammation was even ~15% higher than that achieved with the commercial cream. Selected formulations could be potential candidates as new vehiculation systems for mometasone furoate. The presence of hyaluronic acid in glyceroethohyalurosomes makes them the best candidates in preventing/treating skin inflammatory lesions.
Impaired wound healing in patients with type 2 diabetes (DM2) is characterized by chronic inflammation, which delays wound closure. Specialized pro-resolving lipid mediators (SPMs) are bioactive ...molecules produced from essential polyunsaturated fatty acids (PUFAs), principally omega-3 docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). SPMs are potent regulators of inflammation and have been used to suppress chronic inflammation in peripheral artery disease, non-alcoholic fatty liver disease, and central nervous system syndromes. LIPINOVA® is a commercially available safe-grade nutritional supplement made from a fractionated marine lipid concentrate derived from anchovy and sardine oil that is rich in SPMs and EPA, as well as DHA precursors. Here, we assessed the effect of LIPINOVA® in wound dressing applications. LIPINOVA® showed biocompatibility with keratinocytes and fibroblasts, reduced the abundance of pro-inflammatory macrophages (Mφ1), and promoted in vitro wound closure. Daily application of the marine oil to open wounds made by punch biopsy in db/db mice promoted wound closure by accelerating the resolution of inflammation, inducing neoangiogenesis and Mφ1/Mφ2 macrophage polarization. In conclusion, LIPINOVA® displays pro-resolutive properties and could be exploited as a therapeutic agent for the treatment of diabetic ulcers.
Extracellular matrix (ECM) changes after myocardial infarction (MI) need precise regulation, and next-generation sequencing technologies provide omics data that can be used in this context. We ...performed a meta-analysis using RNA-sequencing transcriptomic datasets to identify genes involved in post-MI ECM turnover. Eight studies available in Gene Expression Omnibus were selected following the inclusion criteria. We compare RNA-sequencing data from 92 mice submitted to permanent coronary ligation or sham, identifying differentially expressed genes (p-value < 0.05 and Log2FoldChange ≥ 2). Functional enrichment analysis was performed based on Gene Ontology biological processes (BPs). BPs implicated in response to extracellular stimulus, regulation of ECM organization, and ECM disassembly were detected soon after ischemia onset. ECM disassembly occurred between days one to seven post-MI, compared with ECM assembly from day seven onwards. We identified altered mRNA expression of 19 matrix metalloproteinases and four tissue inhibitors of metalloproteinases at post-infarcted ECM remodeling and altered transcriptomic expression of 42 genes encoding 26 collagen subunits at the fibrotic stage. To our knowledge, this is the first meta-analysis using RNA-sequencing datasets to evaluate post-infarcted cardiac interstitium healing, revealing previously unknown mechanisms and molecules actively implicated in ECM remodeling post-MI, which warrant further validation.
•Liquorice extract (LQC) was successfully obtained from Glycyrrhiza glabra L. roots.•LQC extract was incorporated into conventional and innovative vesicles.•LQC loaded vesicles protected fibroblasts ...against H2O2 induced oxidative stress.•LQC loaded vesicles were able to inhibit the onset of skin damage.
Liquorice extract, obtained by percolation in ethanol of Glycyrrhiza glabra L. roots, was incorporated in liposomes and hyalurosomes, new phospholipid-sodium hyaluronate vesicles, and their protective effect against oxidative stress skin damages was probed. As a comparison, raw glycyrrhizin was also tested. All the vesicles were small in size (≤100nm), with a highly negative zeta potential ensuring long-term stability, and able to incorporate a high amount of the extract. In vitro tests showed that the liquorice extract loaded in vesicles was able to scavenge DPPH free radical (80% inhibition) and to protect 3T3 fibroblasts against H2O2-induced oxidative stress, restoring the normal conditions. By contrast, glycyrrhizin showed poor antioxidant activity, and was not able to efficiently counteract the oxidative effect of H2O2. In addition, the incorporation of the liquorice extract into the vesicular systems promoted the proliferation and migration of 3T3 fibroblasts, favouring the closure of the scratched area. In vivo anti-inflammatory tests on mice confirmed the ability of the proposed nanosystems to improve the local efficacy of the extract, favouring the re-epitelization process.
Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of ...previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.
Candida auris has unprecedently emerged as a multidrug resistant fungal pathogen, considered a serious global threat due to its potential to cause nosocomial outbreaks and deep-seated infections with ...staggering transmissibility and mortality, that has put health authorities and institutions worldwide in check for more than a decade now. Due to its unique features not observed in other yeasts, it has been categorised as an urgent threat by the Centers for Disease Control and Prevention and other international agencies. Moreover, epidemiological alerts have been released in view of the increase of healthcare-associated C. auris outbreaks in the context of the COVID-19 pandemic. This review summarises the current evidence on C. auris since its first description, from virulence to treatment and outbreak control, and highlights the knowledge gaps and future directions for research efforts.
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