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INFLUENCE OF GAMMA RADIATION ON AMPHOTERICIN B INCORPORATED IN PVP HYDROGEL AS AN ALTERNATIVE TREATMENT FOR CUTANEOUS LEISHMANIOSIS
Acta Tropica ( IF 2.7 ) Pub Date : 2020-12-30 , DOI: 10.1016/j.actatropica.2020.105805
Maria José Alves de Oliveira , Gethzemani Mayeli Estrada Villegas , Flávia Daniela Motta , Omar Fabela-Sánchez , Arián Espinosa-Roa , Wesley Luzetti Fotoran , Janaína Capelli Peixoto , Fabia Tomie Tano , Ademar Benévolo Lugão , Pablo Antonio Salvador Vásquez

Amphotericin B (Amph-B) is an antifungal drug used intravenously for the treatment of leishmaniasis. Side-effects from Amph-B treatment can arise such as cardiac arrhythmia and renal dysfunctions, which will lead to discontinuation of treatment. Unfortunately, patients in endemic countries do not have access to alternative therapies. The objective of this study was to analyze the effects of Cobalt-60 gamma irradiation on crosslinking polymeric hydrogels (Hydg) and the incorporation of Amph-B into the gel as a controlled-release drug delivery alternative. Polyvinylpyrrolidone (PVP)/Amph-B solutions were irradiated with 15 kGy at 0°C and 25°C. The drug's stability was ascertained by UV-visible spectrometry, liquid chromatography/mass spectrometry and proton nuclear magnetic resonance. Irradiated Hydg/Amph-B achieved similar stability to the standard Amph-B solution and was enough to promote hydrogel crosslinking. In vitro trials were carried out to ensure Amph-B was still biologically active after irradiation. The results from flow cytometry and MTT assay show that Amph-B had an IC50 = 16.7 nM. A combination of Hydg at 1.324 gmL−1 and Amph-B at 25.1 nM for 24 hours lead to the greatest inhibition of L. amazonensis promastigotes, and could be used as an alternative treatment method for cutaneous leishmaniosis.



中文翻译:

γ射线辐照对PVP水中两性霉素B替代治疗的影响

两性霉素B(Amph-B)是静脉注射用于治疗利什曼病的抗真菌药物。Amph-B治疗可能会产生副作用,例如心律不齐和肾功能不全,这将导致治疗中断。不幸的是,流行国家的患者无法获得替代疗法。这项研究的目的是分析钴60γ射线辐照对交联聚合物水凝胶(Hydg)的影响,以及将Amph-B掺入凝胶中作为控释药物的替代方法。在0°C和25°C用15 kGy辐照聚乙烯吡咯烷酮(PVP)/ Amph-B溶液。该药物的稳定性通过紫外可见光谱,液相色谱/质谱和质子核磁共振确定。进行了体外试验,以确保辐照后Amph-B仍然具有生物活性。流式细胞仪和MTT分析的结果表明,Amph-B的IC 50  = 16.7 nM。1.324 gmL -1的Hydg和25.1 nM的Amph -B的组合在24小时内可最大程度地抑制亚马逊L. amazonensis前鞭毛体,并可用作皮肤利什曼病的替代治疗方法。

更新日期:2020-12-30
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