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The present study aimed to prepare and optimize lamotrigine-loaded bovine serum albumin nanoparticles (LAM-NP) using the Quality by Design (QbD) approach and to investigate both the and effects of different cross-linking agents glutaraldehyde (GLUT), glucose (GLUC) and 1-(3-dimethylaminutesopropyl)-3-ethylcarbodiimide hydrochloride (EDC) on intranasal applicability. Cross-linked LAM-NP from EDC (NP-EDC-1) showed the lowest Z-average value (163.7 ± 1.9 nm) and drug encapsulation efficacy (EE%) of 97.31 ± 0.17%. The drug release of GLUC cross-linked LAM-NP (NP-GLUC-9), glutaraldehyde cross-linked LAM-NP (NP-GLUT-2), and NP-EDC-1 at blood circulation conditions was higher than the initial LAM. The results of the blood-brain barrier parallel artificial membrane permeability assay (BBB-PAMPA) showed an increase in the permeability of LAM through the BBB with NP-GLUC-9 and an increase in flux with all selected formulations. The study showed that LAM diffusion from the selected formulations through the human nasal mucosa was higher than in case of initial LAM. The cytotoxicity study indicated that BSA-NP reduced LAM toxicity, and GLUC 9 mM and EDC 1 mg could be alternative cross-linking agents to avoid GLUT 2% v/v toxicity. Furthermore, permeability through Caco-2 cells showed that nasal epithelial transport/absorption of LAM was improved by using BSA-NPs. The use of BSA-NP may be a promising approach to enhance the solubility, permeability through BBB and decrease the frequency of dosing and adverse effects of LAM.

The present study aimed to develop and compare the intranasal applicability of favipiravir-loaded aspasomes (FAV-ASPs) using film hydration method, and favipiravir-loaded niosomes (FAV-NIOs) using ethanol injection method. The FAV-ASP and FAV-NIO formulations were characterized according to nanoparticulate characteristics (DLS, drug loading, drug encapsulation efficacy, droplet size distribution), drug release and permeability behavior. The optimized FAV-ASP formulation (FAV-ASP8) consisted of FAV, ascorbyl palmitate, Span® 60 and cholesterol (30:25:25:50 w/w) with nano-scale size range (292.06 ± 2.10 nm), narrow polydispersity index (PDI) value (0.36 ± 0.03), adequate zeta potential (-74.73 ± 3.28 mV) and acceptable encapsulation efficiency (55.33 ± 0.41%). The optimized FAV-NIO formulation (FAV-NIO9) contained FAV, Span® 60 and cholesterol (30:30:40 ) with nano-scale size range (167.13 ± 1.60 nm), narrow PDI value (0.07 ± 0.01), adequate zeta potential (-27.1 ± 1.24 mV) and acceptable encapsulation efficiency (51.30 ± 0.69%). FAV-ASP8 and FAV-NIO9 were suitable for spraying into the nasal cavity (droplet size distribution <200 µm). In vitro drug release and permeability studies demonstrated enhanced solubility and increased blood-brain barrier (BBB) permeability of FAV formulations, respectively. The ex vivo human nasal permeability study revealed that FAV diffusion from FAV-ASP8 was higher than from FAV-NIO9 or initial FAV. Furthermore, the in vivo animal study showed that FAV-ASP8 had a higher BBB penetration compared to FAV-NIO9 and pure FAV. The in vitro-in vivo correlation study showed good correlation between the in vitro and the in vivo pharmacokinetic data. FAV-ASP8 for nose-to-brain delivery system could be a promising formulation to improve FAV bioavailability compared to FAV-NIO9.

Autosomal dominant non-syndromic hearing loss (ADNSHL) is a genetically heterogenic condition. The transformation/transcription domain associated protein (TRRAP) gene has been recently associated with ADNSHL, and only four variants of the gene have so far been reported in this disease. Here, we report on a Hungarian ADNSHL family in which the affected individuals exhibited sensorineural hearing loss with similar clinical symptoms, including initial impaired high frequencies that subsequently affected speech and lower frequencies. Whole exome sequencing and screening of the shared genetic variants of the affected individuals was performed. Our results revealed a novel heterozygous missense variant (NM_001244580.2, c.5360A>G, p.Lys1787Arg) in the TRRAP gene. This variant is completely co-segregated with hearing impairment. It is present in a heterozygous form in the affected mother and daughter but not carried by any unaffected family members. This study highlights the importance of elucidating the germline genetic background of ADNSHL, which may help to predict individual risk and the risk of family members. This will improve prevention, screening, and therapeutic measures for each patient and hearing loss-prone families.

Ivermectin, an antiparasitic drug, has been repurposed for COVID-19 treatment during the SARS-CoV-2 pandemic. Although its antiviral efficacy was confirmed early in vitro and in preclinical studies, its clinical efficacy remained ambiguous. Our purpose was to assess the efficacy of ivermectin in terms of time to viral clearance based on the meta-analysis of available clinical trials at the closing date of the data search period, one year after the start of the pandemic. This meta-analysis was reported by following the PRISMA guidelines and by using the PICO format for formulating the question. The study protocol was registered on PROSPERO. Embase, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), bioRvix, and medRvix were searched for human studies of patients receiving ivermectin therapy with control groups. No language or publication status restrictions were applied. The search ended on 1/31/2021 exactly one year after WHO declared the public health emergency on novel coronavirus. The meta-analysis of three trials involving 382 patients revealed that the mean time to viral clearance was 5.74 days shorter in case of ivermectin treatment compared to the control groups [WMD = −5.74, 95% CI (−11.1, −0.39), p = 0.036]. Ivermectin has significantly reduced the time to viral clearance in mild to moderate COVID-19 diseases compared to control groups. However, more eligible studies are needed for analysis to increase the quality of evidence of ivermectin use in COVID-19.