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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