Ultrasonically Assisted Polysaccharide Microcontainers for Delivery of Lipophilic Antitumor Drugs: Preparation and in Vitro Evaluation.

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 µM (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.

Inter-chromosomal variation in aberration frequencies in human lymphocytes exposed to charged particles of LET between 0.5 and 55 keV/µm.

PURPOSE: To investigate the distribution of chromosomal aberrations in chromosomes 2, 8 and 14 induced by charged particles, using the fluorescence in situ hybridisation (FISH) technique. METHODS: Irradiation of peripheral blood from six healthy volunteers (four male and two female) was performed at the accelerators of the Joint Institute for Nuclear Research (JINR) in Dubna (Russia). Whole blood samples were irradiated with 2 and 3 Gy of protons (170 MeV/nucleon (n), linear energy transfer (LET) ≈ 0.5 keV/µm), 3.5 Gy of (12)C ions (480 MeV/n, LET = 10.6 keV/µm), 3 Gy of (12)C ions 500 MeV/n, LET = 12 keV/µm), 4 Gy of (7)Li ions (30 MeV/n, LET ≈ 20 keV/µm) and 3 Gy of (11)B ions (32 MeV/n, LET ≈ 55 keV/µm). Chromosomal aberrations were analysed in metaphase and prematurely condensed chromosomes (PCC) induced in G(2)-cells using calyculin A. Chromosomes 2, 8 and 14 were painted in different colours and aberrations scored with the help of an image-analysis system. RESULTS: Chromosome 2 was generally less sensitive than expected on the basis of its DNA content. A higher than expected frequency of exchanges was found in chromosomes 8 and 14. On average, the dicentric frequency in chromosome 2 was higher than the translocation frequency, whereas variable dicentric to translocation ratios were observed in chromosomes 8 and 14. When aberrations in all painted chromosomes were summed up the ratio was close to 1. The frequency of complex aberrations correlated with LET. CONCLUSION: In lymphocytes of donors studied in this work chromosome 2 appears to be consistently less sensitive to protons and heavy ions than chromosomes 8 and 14. Complex aberrations appear to be a potential marker of radiation quality.