Nanoplasmonic sensing as a rapid and sensitive methodology to investigate tolvaptan loaded plant-derived nanovesicles and liposomes

Shishir Jaikishan , Ramila Mammadova , Rui Chen , Feby Pratiwi , Gabriella Pocsfalvi , Seppo J. Vainio , Susanne K. Wiedmer
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Abstract

Plant-derived nanovesicles (PDNVs) are potential next generation carriers for drug delivery. However, the systemic incorporation of drugs into PDNVs and their quality control still needs extensive research. Previous works showed that Solanum lycopersicum (tomato) fruit is an excellent resource for the high yield manufacturing of tomato PDNVs. Tomato PDNVs have anti-inflammatory activity in vitro which could be further increased by the loading of a lipophilic natural compound, like curcumin. Recently, tolvaptan, a synthetic selective vasopressin V2-receptor antagonist drug was also successfully loaded into tomato PDNVs. In this work, we have advanced the analysis of native and loaded PDNVs and compared them with liposomes using nanoplasmonic sensing (NPS). Tolvaptan was loaded into liposomes composed of phosphatidyl choline (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and 1,2-palmitoyl-oleoyl-sn-glycero-3-phosphoserine with and without cholesterol. In addition to NPS, micro differential scanning calorimetry was used to get a deeper understanding of the interactions between tolvaptan and the various liposome compositions. The result of the comparative NPS study showed that tolvaptan can be successfully incorporated both into PDNVs and liposomes of different compositions. The PDNV/tolvaptan and liposome/tolvaptan systems were found to be stable. Due to the low water solubility of tolvaptan, the developed PDNV/tolvaptan or liposome/tolvaptan nanoparticle complexes may present a novel and effective strategy for nanodrug delivery.
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纳米等离子体传感作为一种快速、灵敏的方法来研究负载tolvaptan的植物源纳米囊泡和脂质体
植物源性纳米囊泡(pdnv)是潜在的下一代药物递送载体。然而,药物系统入药pdnv及其质量控制仍需要广泛的研究。前期研究表明,番茄果实是生产番茄pdnv的优良资源。番茄pdnv在体外具有抗炎活性,可以通过加载亲脂性天然化合物(如姜黄素)进一步增强。最近,合成的选择性抗利尿激素v2受体拮抗剂托伐普坦也成功地装载到番茄pdnv中。在这项工作中,我们进一步分析了天然pdnv和负载pdnv,并使用纳米等离子体传感(NPS)将它们与脂质体进行了比较。Tolvaptan被装入由磷脂酰胆碱(1-棕榈酰-2-油酰- n-甘油-3-磷酸胆碱或1,2-二棕榈酰- n-甘油-3-磷酸胆碱)和1,2-棕榈酰-油酰- n-甘油-3-磷酸丝氨酸(含或不含胆固醇)组成的脂质体中。除了NPS外,微差扫描量热法还被用于更深入地了解托伐普坦与各种脂质体组成之间的相互作用。对比NPS研究结果表明,托伐普坦可以成功地结合到pdnv和不同组成的脂质体中。发现PDNV/tolvaptan和脂质体/tolvaptan体系是稳定的。由于托伐普坦的水溶性较低,所开发的PDNV/托伐普坦或脂质体/托伐普坦纳米颗粒复合物可能是一种新的有效的纳米药物递送策略。
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