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.
- Downloaded 206 times
- Download rankings, all-time:
- Site-wide: 67,891 out of 88,882
- In biochemistry: 2,132 out of 2,969
- Year to date:
- Site-wide: 38,406 out of 88,882
- Since beginning of last month:
- Site-wide: 24,966 out of 88,882
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!