Dehghani Pouya, Varshosaz Jaleh, Mirian Mina, Minaiyan Mohsen, Kazemi Mohammad, Bodaghi Mahdi
Novel Drug Delivery Systems Research Center, Department of Pharmaceutics, Faculty of Pharmacy, Isfahan University of Medical Sciences, PO Box 81745-359, Isfahan, Iran.
Department of Pharmaceutical Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
Pharm Res. 2024 Feb;41(2):263-279. doi: 10.1007/s11095-023-03648-0. Epub 2024 Jan 23.
Exosomes are extracellular vesicles in the range of 40-150 nm released from the cell membrane. Exosomes secreted by keratinocytes can communicate with other keratinocytes and immune cells with specific biomarkers at their surface, which may be effective on inflammation of psoriasis and its pathogenesis.
The present study aimed to formulate and study effectiveness of an exosomal delivery system of tofacitinib (TFC).
TFC was loaded by different methods in exosomes and then characterized for particle size, zeta potential, drug loading efficiency, and release efficiency. By comparing these parameters, the probe sonication method was chosen to load TFC into exosomes. The MTT assay was used to compare the cytotoxicity of the free drug with the TFC-loaded exosomes (TFC-Exo), and Real-time PCR was used to determine the expression levels of several genes involved in psoriasis expressed in the A-431 keratinocyte and their suppression after treatment. Animal model of psoriasis was induced in BALB/c mice by imiquimod and the efficacy of free TFC, and TFC-Exo were studies on macroscopic appearance and histopathological symptoms.
Exosomes encapsulating TFC showed lower cytotoxicity in MTT assay, higher suppression the expression of TNF-a, IL-23, IL-6, and IL-15 genes in real-time PCR and better therapeutic effect on animal models compered to free TFC.
This method of drug delivery for TFC may be effective on enhancing its therapeutic effects and reduction its side effects favorably in chronic administration.
外泌体是从细胞膜释放的40-150纳米范围内的细胞外囊泡。角质形成细胞分泌的外泌体可通过其表面的特定生物标志物与其他角质形成细胞和免疫细胞进行通讯，这可能对银屑病的炎症及其发病机制有效。
本研究旨在制备并研究托法替布（TFC）的外泌体递送系统的有效性。
通过不同方法将TFC负载到外泌体中，然后对其粒径、zeta电位、载药效率和释放效率进行表征。通过比较这些参数，选择探针超声法将TFC负载到外泌体中。采用MTT法比较游离药物与负载TFC的外泌体（TFC-Exo）的细胞毒性，采用实时定量PCR法测定A-431角质形成细胞中几种银屑病相关基因的表达水平及其在治疗后的抑制情况。通过咪喹莫特诱导BALB/c小鼠银屑病动物模型，研究游离TFC和TFC-Exo在宏观外观和组织病理学症状方面的疗效。
在MTT试验中，包裹TFC的外泌体显示出较低的细胞毒性，在实时定量PCR中对TNF-α、IL-23、IL-6和IL-15基因的表达有更高的抑制作用，并且与游离TFC相比，对动物模型具有更好的治疗效果。
这种TFC的药物递送方法可能有效地增强其治疗效果，并在长期给药中有利地减少其副作用。
