Novel lipophilic SN38 prodrug forming stable liposomes for colorectal carcinoma therapy

International Journal of Nanomedicine
Jing XingMin Ji

Abstract

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, moei...Continue Reading

Citations

Jun 28, 2020·AAPS PharmSciTech·Laura CabezaConsolación Melguizo
Jul 28, 2020·Nanomaterials·Chunhua Yang, Didier Merlin
Apr 4, 2021·Acta Biomaterialia·Rui SangWei Deng
Sep 1, 2021·Pharmaceutical Research·Sifei HanNatalie Trevaskis

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BETA
flow cytometry
xenograft
transmission electron microscopy

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