Engineering artesunate-loaded micelles using spray drying for pulmonary drug delivery
Novel d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) micelles containing the anti-cancer drug artesunate (ART) were developed in a dry powder form for inhalation for the treatment of lung cancer. Targeted delivery to the lungs via inhalation presents a challenge, and the current study involved the development, characterization, and cytotoxicity determination of the dry powder formulations. TPGS micelles encapsulating ART were successfully prepared using thin-film hydration method, followed by the preparation of a dry powder formulation through spray-drying, which included lactose and leucine as carrier molecules. Characterization of the dry powder formulation using Sympatec laser diffraction particle size analyzer and a next generation impactor.
The analysis showed a unimodal particle size distribution with a mean particle size of 3.27 μm and a fine particle fraction of 31%, respectively. Artesunate-loaded micelle dry powder formulation demonstrated higher cytotoxicity against the A549 adenocarcinomic human alveolar basal epithelial cell line when compared to currently used cancer therapies docetaxel and doxorubicin. Overall, this study demonstrates that spray-dried micelles containing artesunate have the potential to be used as a dry powder formulation for inhalation in the treatment of lung cancer.
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Materials
ART was purchased from Tokyo Chemical Industry UK Ltd. (Oxford, UK) and TPGS (MW = 1513) was obtained from Sigma-Aldrich (St Louis, USA). Methanol and chloroform were purchased from VMR Chemicals (Leicestershire, UK). Lactose, l-leucine, 0.05% w/v Thiazolyl blue tetrazolium bromide (MTT) and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich (St Louis, USA).
Satyanarayana Somavarapu, Acom Sornsute, Jeanne Trill, Hend E. Abdelhakim, Dinithi Goonatilaka, Ananth S. Pannala, Kevin M.G. Taylor, Engineering artesunate-loaded micelles using spray drying for pulmonary drug delivery,
Journal of Drug Delivery Science and Technology, Volume 86, 2023, 104641, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104641.
See also the interesting video on Vitamin E TPGS: