English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Background: SN38 (7-ethyl-10-hydroxy camptothecin), as a potent metabolite of irinotecan, is highly efficacious in cancer treatment. However, the clinical utility of SN38 has been greatly limited due to its undesirable properties, such as poor solubility and low stability. Materials and methods: In order to overcome these weaknesses, moeixitecan, a lipophilic SN38 prodrug containing a SN-38, a trolox, a succinic acid linker, and a hexadecanol chain, was loaded into liposomal nanoparticles by ethanol injection method. Results: Experiments showed that the moeixitecan-loaded liposomal nanoparticles (MLP) with a diameter of 105.10±1.49 nm have a satisfactory drug loading rate (90.54±0.41%), high solubility and stability, and showed sustained release of SN38. Notably, MLP exhibited better antitumor activity against human colon adenocarcinoma cells than irinotecan, a FDA-approved drug for the treatment of advanced colorectal cancer. Furthermore, xenograft model results showed that MLP outperformed irinotecan in terms of pharmacokinetics, in vivo therapeutic efficacy and safety. Finally, we used molecular dynamic simulations to explore the association between the structure of MLP and the physical and functional properties of MLP, moeixitecan molecules in MLP folded themselves inside the hydrocarbon chain of the lipid bilayer, which led an increased acyl chain order of the lipid bilayer, and therefore enhanced the lactone ring stability protecting it from hydrolysis. Conclusion: Our MLP constructing strategy by liposome engineering technology may serve a promising universal approach for the effective and safe delivery of lipophilic prodrug.

<p>Novel lipophilic SN38 prodrug forming stable liposomes for colorectal carcinoma therapy</p>