The interplay between trehalose and dextran as spray drying precursors for cationic liposomes
Successful oral delivery of liposomes requires formulations designed to withstand harsh gastrointestinal conditions, e.g., by converting to solid-state followed by loading into gastro-resistant delivery devices. The hypothesis was that the use of dextran-trehalose mixtures for spray drying would improve the rehydration kinetics of dried liposomes. The objectives were to determine the protective capacity of trehalose-dextran dehydration precursors and to increase the concentration of liposomes in the dry formulation volume.
The study successfully demonstrated that 8.5% dextran combined with 76.5% trehalose protected CAF®04 liposomes during drying, with the liposome content maintained at 15% of the dry powder. Accordingly, the rehydration kinetics were slightly improved in formulations containing up to 8.5% dextran in the dry powder volume. Additionally, a 2.4-fold increase in lipid concentration (3mM vs 7.245 mM) was achieved for spray dried CAF®04 liposomes. Ultimately, this study demonstrates the significance of trehalose as a primary carrier during spray drying of CAF®04 liposomes and highlights the advantage of incorporating small amounts of dextran to tune rehydration kinetics of spray-dried liposomes.
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Materials
N,N-dimethyl-N,N-dioctadecylammonium bromide (DDA) (purity 99.9%) and glycerolipid monomycoloyl glycerol (MMG) (purity 99%) were obtained from Niels Clauson-Kaas A/S (Farum, Denmark). Trehalose dihydrate (purity 99.9%) and Dextran 6000 (purity 99%) were from Sigma-Aldrich (St. Louis, Missouri, USA). All reagents used were of analytical grade.
Anitta Lutta, Matthias M. Knopp, Matteo Tollemeto, Gabriel K. Pedersen, Signe T. Schmidt, Holger Grohganz, Line Hagner Nielsen, The interplay between trehalose and dextran as spray drying precursors for cationic liposomes,
International Journal of Pharmaceutics, 2024, 123798, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.123798.
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