Non-toxic polymer nanovectors for improved delivery of dexamethasone

Dexamethasone (Dex) is a highly insoluble front-line drug used in cancer therapy. Data from clinical trials indicates that the pharmacokinetics of Dex vary considerably between patients and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Non-toxic, fully biodegradable Dex loaded nanovectors (NV) were formulated, via simple direct hydration within 10 min, as a vehicle to extend exposure and distribution in vivo. Dex-NV were just as effective as the free drug against primary human leukemia cells in vitro and in vivo. Importantly, high levels of DMSO solvent were not required in the NV formulations. Broad distribution of NV was seen rapidly following inoculation into mice. NV accumulated in major organs, including bone marrow and brain, known sanctuary sites for ALL.

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Fig: Fabrication of Dex-loaded Nanovectors (Dex-NV). (A) Schematic outlining the fabrication of Dex-NV comprising mPEG-PTMC copolymers. (B) DLS size measurements of NV loaded with Dex (Black) or DiR (Red) before (solid) and after (dashed lines) 0.2 µm filtration. (C) DLS correlogram data of NV (black) or free Dex (blue), before (solid) and after (dashed lines) filtration. Dexdexamethasone, DiR 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide, DLS dynamic light scattering.

The study describes a non-toxic, more easily scalable system for improving Dex solubility for use in cancer and can be applied to other medical conditions associated with inflammation.

Ede, B.C., Diamanti, P., Williams, D.S. et al. Non-toxic polymer nanovectors for improved delivery of dexamethasone. Sci Rep 11,17263 (2021). https://doi.org/10.1038/s41598-021-96797-4

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