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

Shuddhodana; Wong, Pooi Wen Kathy; Judeh, Zaher

Materials Science and Engineering: C, 2020, vol 108pp. 110410

DOI:10.1016/j.msec.2019.110410

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.

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