Davari Afshin, Hajjaran Homa, Khamesipour Ali, Mohebali Mehdi, Mehryab Fatemeh, Shahsavari Saeed, Shekari Faezeh
Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Parasitol. 2023 Oct-Dec;18(4):514-525. doi: 10.18502/ijpa.v18i4.14260.
Recent studies have shown an increasing number of patients with cutaneous leishmaniasis (CL) who do not respond to pentavalent antimonials as the first line of treatment for CL. Nanocarriers such as extracellular vesicles (EVs) are efficient vehicles that might be used as drug delivery systems for the treatment of diseases. Therefore, we aimed to isolate and characterize the EVs of , load them with Amphotericin B (AmB), and investigate the toxicity and efficacy of the prepared drug form.
The EVs of were isolated, characterized, and loaded with amphotericin B (AmB), and the EVs-Amphotericin B (EVs-AmB) form was synthesized. Relevant in vitro and in vivo methods were performed to evaluate the toxicity and efficacy of EVs-AmB compared to the control.
The anti-leishmanial activity of the EVs-AmB showed a higher percentage inhibition (PI%) ( = 0.023) compared to the AmB at different concentrations and time points. Obtained data showed a significant increase in the lesion size and parasite load in the lesion, PBS, and EVs mice groups in comparison with EVs-AmB, AmB, and Glucantime groups ( < 0.05), EVs-AmB had a significant decrease in lesion sizes in comparison with AmB ( < 0.05). Results showed that EVs-AmB decreased its toxicity to the kidneys and liver ( < 0.05).
EVs-AmB improved the efficacy of AmB in mouse skin lesions and reduced hepatorenal toxicity. Furthermore, EVs could be a promising nanoplatform for the delivery of AmB in CL caused by .
最近的研究表明,越来越多的皮肤利什曼病(CL)患者对五价锑作为CL一线治疗药物无反应。细胞外囊泡(EVs)等纳米载体是高效的载体,可用作治疗疾病的药物递送系统。因此,我们旨在分离和表征[具体生物名称]的EVs,用两性霉素B(AmB)装载它们,并研究制备的药物形式的毒性和疗效。
分离、表征[具体生物名称]的EVs,并用两性霉素B(AmB)装载,合成EVs-两性霉素B(EVs-AmB)形式。与对照组相比,采用相关的体外和体内方法评估EVs-AmB的毒性和疗效。
在不同浓度和时间点,与AmB相比,EVs-AmB的抗利什曼活性显示出更高的抑制百分比(PI%)(P = 0.023)。获得的数据显示,与EVs-AmB、AmB和葡糖胺组相比,PBS和EVs小鼠组的病变大小和病变中的寄生虫负荷显著增加(P < 0.05),与AmB相比,EVs-AmB的病变大小显著减小(P < 0.05)。结果表明,EVs-AmB对肾脏和肝脏的毒性降低(P < 0.05)。
EVs-AmB提高了AmB在小鼠皮肤病变中的疗效,并降低了肝肾毒性。此外,EVs可能是在由[具体生物名称]引起的CL中递送AmB的有前景的纳米平台。