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Critical parameters dictating efficiency of membrane-mediated drug transfer using nanoparticles

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Title: Critical parameters dictating efficiency of membrane-mediated drug transfer using nanoparticles
Authors: Abbasi, Saed Browse this author
Kajimoto, Kazuaki Browse this author →KAKEN DB
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Nanoemulsion
Drug transfer
Drug release
Drug delivery
Cytosolic delivery
Issue Date: 20-Dec-2018
Publisher: Elsevier
Journal Title: International journal of pharmaceutics
Volume: 553
Issue: 1-2
Start Page: 398
End Page: 407
Publisher DOI: 10.1016/j.ijpharm.2018.10.042
Abstract: Curcumin, a low molecular weight, hydrophobic compound, exhibits strong anti-cancer effects and has a high margin of safety. However, its poor water solubility, rapid metabolism and degradation make it relatively ineffective, but intracellular delivery using nanoparticles (NPs) would solve these problems. In this study, we formulated curcumin in two-structurally distinct NPs: a nanoemulsion (Cur-NE) and a Niosome (Cur-NIO), evaluated their in-vitro cytotoxic effects and examined their mechanisms of drug delivery. The use of Cur-NIO resulted in an unexpected increase in the intracellular accumulation of curcumin and induced a potent cytotoxic effect compared to Cur-NE. To our surprise, however, the effects of the endocytosis of NIO as well as that for NE on the cellular delivery of curcumin were negligible. Consequently, we concluded that Cur-NIO delivers curcumin directly to the cytosol via transfer from the NIO to the cell membrane. The results of Forster resonance energy transfer (FRET) and phase-transfer studies indicate that Cur-NIO exhibits efficient transfer into model membranes or organic interfaces. Moreover, we found that Cur-NE shows a poor transfer efficiency. This could be due to the presence of a hydrophobic oil core that reduces the probability of curcumin to transfer upon contact with the membrane. To the best of our knowledge, this is the first study of the effect of NP structure on the membrane-mediated transfer efficiency of low molecular weight, hydrophobic compounds.
Rights: ©2018, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 原島 秀吉

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