Despite many efforts to improve the transdermal permeability of drugs, most of them are blocked by the skin barrier. Niacinamide (NAC) is a Biopharmaceutics Classification System class I drug with high aqueous solubility and intestinal permeability. Due to the high solubility and intestinal permeability of NAC, the development of new formulations is insufficient as transdermal, injection etc. Thus, this study aimed to develop the novel NAC formulation with improved skin permeability and secured stability. The NAC formulation approach is to first select a solvent that improves skin permeability, and then select a second penetration enhancer to determine the final formulation. All formulations were evaluated for skin permeability using an artificial membrane (Strat-M®). The optimal formulation (non-ionic formulations (NF1) consisted of NAC/Tween®80 = 1:1 wt ratio in dipropylene glycol [DPG]) showed the highest permeability in all formulations in PBS buffer (pH 7.4). The thermal properties of NF1 were altered. Moreover, NF1 maintained a stable drug content, appearance, and pH value for 12 months. In conclusion, DPG had an excellent effect in increasing the NAC permeation, and Tween®80 played a boosting role. Through this study, an innovative NAC formulation was developed, and good results are expected for human transdermal research.

2023-06-06·Trials

Improvement of synaptic plasticity and cognitive function in RASopathies-a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS).

Article

作者: Kehl, Victoria ; Jung, Nikolai H ; Wahlländer, Ute ; Blankenstein, Christiane ; Brich, Louisa ; Schossow, Beate ; Mall, Volker ; Janke, Viktoria ; Egert-Schwender, Silvia ; Zenker, Martin

BACKGROUNDCognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies.METHODSWithin this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I-III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV).DISCUSSIONThe study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition.TRIAL REGISTRATIONThe clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www.CLINICALTRIALSgov ; date of registration: 04/11/2018) and in EudraCT (number 2016-005022-10).

2023-06-01·Archives of Industrial Hygiene and Toxicology

A new strategy to achieve high antimicrobial activity: green synthesised silver nanoparticle formulations with Galium aparine and Helichrysum arenarium

Article

作者: Derman, Serap ; Coksu, Irem ; Ozbek, Tulin ; Gencer, Merve ; Ozdemir, Cilem

AbstractSilver nanoparticles (AgNPs), which have recently gained attention due to their antimicrobial activity, can also be produced by green synthesis. The aims of this study were to (i) characterise green synthesized AgNPs using microwave-assisted aqueous extracts of Galium aparine (G-AgNPs) and Helichrysum arenarium (H-AgNPs) and (ii) investigate the combined antimicrobial effects of the G- and H-AgNPs in different ratios. Nanoparticle formation and reactions were determined with UV-Vis spectroscopy. The G-AgNPs were 52.0±10.9 nm in size, with a 0.285±0.034 polydispersity index (PDI), and a -17.9±0.9 mV zeta potential. For H-AgNPs these characteristics were 23.9±1.0 nm, 0.280±0.032, and -21.3±2.7 mV, respectively. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) confirmed that the particles were monodisperse and spherical. The Fourier transform-infrared spectroscopy (FT-IR) results showed the presence of reducing agents that stabilised the AgNPs. Three different nanoformulations (NF-1, NF-2, and NF-3) were prepared by combining these two synthesised nanoparticles in different ratios and their antimicrobial activity was tested against E. coli, S. aureus, C. albicans, and A. flavus. Our study is the first to show that combining AgNPs from two different biological sources can produce effective nanoformulations with improved antibacterial activity against E. coli and S. aureus. These nanoformulations showed lower minimum inhibitory concentrations (31.25 µg/mL against E. coli with all NFs; 62.5 µg/mL for NF-1 and 125 µg/mL for NF-2/3 against S. aureus) than G-AgNPs (62.5 µg/mL for E. coli) or H-AgNPs (125 µg/mL for S. aureus) alone. Their high combined inhibitory effect against E. coli (NF-1–3) was synergistic and against S. aureus (NF-2 and NF-3) potentially additive. Considering such promising results, we believe our study provides some direction for new research and strategies in antimicrobial therapeutics.

100 项与 NF-1 相关的药物交易

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