Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 7, Issue 30, Pages 16581-16589Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.5b04141
Keywords
drug delivery systems; chitosan; xanthan gum; multicellular tumor spheroids; ultrasonication; microcontainers
Funding
- RFBR [12-04-31687 mol_a]
- Ministry of Education and Science of the Russian Federation
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High toxicity, poor selectivity, and severe side effects are major drawbacks of anticancer drugs. Various drug delivery systems could be proposed to overcome these limitations. The aim of this study was to fabricate polysaccharide microcontainers (MCs) loaded with thymoquinone (TQ) by a one-step ultrasonication technique and to study their cellular uptake and cytotoxicity in vitro. Two MC fractions with a mean size of 500 nm (MC-0.5) and 2 mu M (MC-2) were prepared and characterized. Uptake of the MCs by mouse melanoma M-3 cells was evaluated in both 2D (monolayer culture) and 3D (multicellular tumor spheroids) models by confocal microscopy, flow cytometry, and fluorimetry. The higher cytotoxicity of the TQ-MC-0.5 sample than the TQ-MC-2 fraction was in good correlation with higher MC-0.5 accumulation in the cells. The MC-0.5 beads were more promising than the MC-2 particles because of a higher cellular uptake in both 2D and 3D models, an enhanced antitumor effect, and a lower nonspecific toxicity.
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