Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 67,594 bioRxiv papers from 298,341 authors.
SN-38 is a chemotherapeutic compound with potent antitumor effects. However, its clinical application is currently limited due to its poor solubility and low stability at physiological pH. Liposomes and cyclodextrins have been long studied for the solubilization and delivery of hydrophobic compounds. Aiming to combine the advantages from both systems, we attempted to develop an SN-38-in-cyclodextrin-in-liposome formulation. We found that the encapsulation of SN-38-SBE-β-CD inclusion complexes in the lumen of liposomes was not possible, owing to the disassembly of liposomes and the formation of lipid nanoparticles, as revealed by size exclusion chromatography and single nanoparticle fluorescence microscopy. Interestingly, the retention time of SN-38 inside SN-38-SBE-β-CD-lipid nanoparticles is higher than in liposomes, whereby SN-38 was directly loaded into the lipid film. The toxicity of purified SN-38-SBE-β-CD-lipid nanoparticles was assayed in cultured cancer cells, showing no therapeutic advantage compared to bulk SN-38-SBE-β-CD complexes. Further formulation optimization, in particular an increased concentration of the nanoparticles, will be necessary to obtain cytotoxicity effects. Moreover, the results highlight the value of fluorescence imaging of single, surface-immobilized nanoparticles, in the development of liposomal delivery systems such as drug-in-cyclodextrin-in-liposomes.
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