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New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment
Pharmaceutics ( IF 4.9 ) Pub Date : 2021-01-12 , DOI: 10.3390/pharmaceutics13010091
Amandine Gendron , Natalie Lan Linh Tran , Julie Laloy , Romain Brusini , Aurélie Rachet , Frédéric Gobeaux , Valérie Nicolas , Pierre Chaminade , Sonia Abreu , Didier Desmaële , Mariana Varna

Cyclosporin A (CsA) is a molecule with well-known immunosuppressive properties. As it also acts on the opening of mitochondrial permeability transition pore (mPTP), CsA has been evaluated for ischemic heart diseases (IHD). However, its distribution throughout the body and its physicochemical characteristics strongly limit the use of CsA for intravenous administration. In this context, nanoparticles (NPs) have emerged as an opportunity to circumvent the above-mentioned limitations. We have developed in our laboratory an innovative nanoformulation based on the covalent bond between squalene (Sq) and cyclosporin A to avoid burst release phenomena and increase drug loading. After a thorough characterization of the bioconjugate, we proceeded with a nanoprecipitation in aqueous medium in order to obtain SqCsA NPs of well-defined size. The SqCsA NPs were further characterized using dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryoTEM), and high-performance liquid chromatography (HPLC), and their cytotoxicity was evaluated. As the goal is to employ them for IHD, we evaluated the cardioprotective capacity on two cardiac cell lines. A strong cardioprotective effect was observed on cardiomyoblasts subjected to experimental hypoxia/reoxygenation. Further research is needed in order to understand the mechanisms of action of SqCsA NPs in cells. This new formulation of CsA could pave the way for possible medical application.

中文翻译:

环孢菌素A的新纳米颗粒制剂:体外评估

环孢菌素A(CsA)是一种具有众所周知的免疫抑制特性的分子。由于CsA还作用于线粒体通透性过渡孔(mPTP)的开口,因此已针对缺血性心脏病(IHD)进行了评估。但是,其在人体中的分布及其理化特性强烈限制了CsA用于静脉内给药的用途。在这种情况下,出现了纳米颗粒(NPs)作为规避上述限制的机会。我们在实验室中开发了一种创新的纳米配方,该配方基于角鲨烯(Sq)和环孢菌素A之间的共价键,从而避免了突发释放现象并增加了载药量。在对生物缀合物进行全面表征后,我们在水性介质中进行了纳米沉淀,以获得大小明确的SqCsA NP。使用动态光散射(DLS),低温透射电子显微镜(cryoTEM)和高效液相色谱(HPLC)进一步表征SqCsA NP,并评估其细胞毒性。由于目标是将它们用于IHD,因此我们评估了两种心脏细胞系的心脏保护能力。在经历实验性缺氧/复氧的心肌母细胞上观察到了强大的心脏保护作用。为了了解SqCsA NP在细胞中的作用机理,需要做进一步的研究。CsA的这种新配方可以为可能的医学应用铺平道路。由于目标是将它们用于IHD,因此我们评估了两种心脏细胞系的心脏保护能力。在经历实验性缺氧/复氧的心肌母细胞上观察到了强大的心脏保护作用。为了了解SqCsA NP在细胞中的作用机理,需要做进一步的研究。CsA的这种新配方可以为可能的医学应用铺平道路。由于目标是将它们用于IHD,因此我们评估了两种心脏细胞系的心脏保护能力。在经历实验性缺氧/复氧的心肌母细胞上观察到了强大的心脏保护作用。为了了解SqCsA NP在细胞中的作用机理,需要做进一步的研究。CsA的这种新配方可以为可能的医学应用铺平道路。
更新日期:2021-01-12
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