Continuous, high-throughput production of artemisinin-loaded supramolecular cochleates using simple off-the-shelf flow focusing device

Shuddhodana, Pooi Wen Kathy Wong, Zaher Judeh

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Lipid cochleates are gaining increasing interest as drug-carriers. However, their preparation relies on conventional batch processes that are complex, time consuming and lack batch-to-batch reproducibility; presenting a bottleneck for clinical translation. We report an efficient continuous preparation process for artemisinin-loaded cochleates (ART-cochleates) using inexpensive off-the-shelf flow focusing device. By carefully controlling the flow focusing parameters, we showed along with the mechanism that, ART-cochleates of uniform and tuneable size (~180 nm in width and ~1030 nm in length) were obtained with low dispersity (0.18 in width and 0.27 in length), narrow size distribution and high reproducibility compared to the batch process. The device achieved high throughput of 11.5 g/day with ART encapsulation of 64.24 ± 2.5% and loading of 83.37 ± 3.68 mg ART/g of cochleates. Art-cochleates were non-toxic and showed sustained in-vitro release of ART with effective transepithelial permeability across intestinal Caco-2 monolayer (~60% and ~25% transport for pure ART and ART-cochleates, respectively) resulting in better in-vitro bioavailability. The off-the-shelf device is envisioned to be highly promising platform for continuous and high-throughput manufacturing of drug-loaded cochleates in a controlled and reproducible manner. It has potential to enable clinical translation of drug-loaded cochleates with predicable drug release, absorption and bioavailability.

Original languageEnglish
Article number110410
JournalMaterials Science and Engineering C
Volume108
ISSN0928-4931
DOIs
Publication statusPublished - Mar 2020
Externally publishedYes
MoE publication typeA1 Journal article-refereed

Bibliographical note

Funding Information:
We thank Nanyang Technological University, Singapore for financial help (RG 13/18).

Publisher Copyright:
© 2019 Elsevier B.V.

Fields of Science

  • Artemisinin
  • Cochleates
  • Continuous production
  • Lipids
  • Liposomes
  • Microfluidic flow focusing

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