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

• Published in: Materials Science & Engineering C 2020-03, Vol.108, p.110410, Article 110410
• Main Authors: Shuddhodana, Wong, Pooi Wen Kathy, Judeh, Zaher
• Format: Article
• Language: English
• Subjects: Artemisinin; Batch processes; Batch processing; Bioavailability; Cochleates; Continuous production; Drug delivery systems; Intestine; Lipids; Liposomes; Materials science; Membrane permeability; Microfluidic flow focusing; Reproducibility; Size distribution; Translation
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.110410

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. [Display omitted] •Developed first continuous in-flow production of drug-loaded cochleates•Continuous process uses cheap and scalable off-the-shelf microfluidic device.•Process produces high throughput uniform cochleates with controlled size, low dispersity and narrow size distribution.•Cochleate self-assembly was explained using computational fluid dynamic simulations.•In-vitro release, and transport of artemisinin demonstrate better oral bioavailability.