Remdesivir-Loaded Nanoliposomes Stabilized by Chitosan/Hyaluronic Acid Film with a Potential Application in the Treatment of Coronavirus Infection

IF 3.2 Q2 CLINICAL NEUROLOGY
Viktoria Milkova, Neli Vilhelmova-Ilieva, Anna Gyurova, Kamelia Kamburova, Ivaylo Dimitrov, Elina Tsvetanova, Almira Georgieva, Milka Mileva
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Abstract

An object of the present study was the development of liposomes loaded with the medicine Veklury® (remdesivir) stabilized by electrostatic adsorption of polysaccharide film formed from chitosans with different physicochemical characteristics and hyaluronic acid. The functionalization of the structures was achieved through the inclusion of an aptamer (oligonucleotide sequence) with specific affinity to the spike protein of the human coronavirus HCoV-OC43. The hydrodynamic size, electrokinetic potential and stability of the structures were evaluated at each step in the procedure. The encapsulation efficiency and loaded amount of remdesivir (99% and 299 µg/mL) were estimated by UV–vis spectroscopy. Our investigations showed manifestation of promising tendencies for prolonged periods of the drug release and increased effectiveness of its antiviral action. Among all studied versions of the delivery system, the most distinguished and suitable in a model coronavirus therapy are the liposomes formed from chitosan oligosaccharides. The cytotoxicity of the liposomes was determined against the HCT-8 cell line. A cytopathic effect inhibition test was used for the assessment of the antiviral activity of the compounds. The virucidal activity and the effect on the viral adsorption of the samples were reported by the end-point dilution method, and the alteration in viral titer was determined as Δlgs compared to untreated controls. The redox-modulating properties of the nanoparticles were studied in vitro in certain/several/a few chemical model systems. Our investigations showed a manifestation of promising tendencies for a prolonged effect of the drug release and increased effectiveness of its antiviral action.
壳聚糖/透明质酸膜稳定负载瑞德西韦的纳米脂质体在冠状病毒感染治疗中的潜在应用
本研究的目的是研制一种载药脂质体,该脂质体是由具有不同物理化学特性的壳聚糖和透明质酸形成的多糖膜静电吸附稳定的。这些结构的功能化是通过包含一个与人类冠状病毒HCoV-OC43刺突蛋白具有特异性亲和力的适体(寡核苷酸序列)实现的。在每个步骤中,对结构的水动力尺寸、电动势和稳定性进行了评估。采用紫外-可见光谱法测定瑞德西韦的包封率(99%)和载药量(299µg/mL)。我们的研究表明,药物释放时间的延长和抗病毒作用的增强是有希望的趋势。在所有已研究的递送系统中,最独特和最适合治疗冠状病毒的是由壳聚糖低聚糖形成的脂质体。测定脂质体对HCT-8细胞株的细胞毒性。采用细胞病变效应抑制试验评价化合物的抗病毒活性。用终点稀释法报告了样品的杀病毒活性和对病毒吸附的影响,并测定了与未处理对照相比病毒滴度的变化为Δlgs。在体外若干化学模型体系中研究了纳米颗粒的氧化还原调节性能。我们的研究显示了有希望的趋势表现为延长药物释放效果和增加其抗病毒作用的有效性。
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来源期刊
Neurology International
Neurology International CLINICAL NEUROLOGY-
CiteScore
3.70
自引率
3.30%
发文量
69
审稿时长
11 weeks
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