YÜCEL Ç. , Değim Z., Yılmaz Ş.

5 th BBBB International Conference, Yunanistan, 1 - 04 Eylül 2013, ss.24

  • Basıldığı Ülke: Yunanistan
  • Sayfa Sayısı: ss.24


Purpose: Evaluation of effectiveness of liposome and nanoparticulate formulations containing doxycycline and sodium taurocholate (NaTC). Investigations of their transport properties through Caco-2 cell lines.


Material and Methods: Doxycycline and NaTC prepared using dry film hydration method using cholesterol and dipalmytoilphosphatidiylcholine (DPPC). Nanoparticles were prepared using emulsion polymerization. Eudragit RS 100 was used as a polymer.

MTT (-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test was performed for studying doxycycline and NaTC (increased paracellular absorbtion due to opening of tight junctions between epithelial cells) effect on the viability of Caco-2 cells.

For matrix metalloproteinase-2 (MMP-2) determination, approximately 5x105 Caco-2 cells were seeded to 35 mm wells1. They were incubated for two days and washed with DMEM. Studied groups were incubated with 1 mL DMEM for 18 h. After cells were centrifugated MMP-2 was determined from the upper clear part of the kit.


Results: According to the MTT test results, doxycycline and NaTC concentration did not exceed 10 µg/mL and 1.875 mM for 24 hours period. The cumulative amount of transported doxycycline from doxycycline and NaTC containing liposome and nanoparticle formulations through apical to basolateral side of Caco-2 cells was found to be 68.4% and 53.4% (n=3) respectively. Apparent permeability coefficients (k) were calculated as 5.83±0.07, 2.13±0.09 (n=3) for doxycycline and NaTC containing liposomes and nanoparticles respectively. Inhibition percentages of MMP-2 were 95.1% and 98.4% with liposome and nanoparticle formulations.


Discussion: Doxycycline is a type of tetracycline antibiotic that plays a key role in the growth and spread of the tumor as it inhibits MMP-2 enzyme and shows an antitumor effect. Based on the secretion of MMP-2 from cancer cells, two formulations containing MMP inhibitor, doxycycline, have been tested and it was found that the growth of the cancer cells was inhibited significantly by developed doxycycline formulations. It was concluded that doxycycline permeability coefficient and cumulative amount of doxycycline % values were found to be higher for liposome formulation compared to nanoparticles. MMP-2 was found to be inhibited more with doxycycline when liposome formulation was used. This suggests that liposome formulation may be more effective and it can be used for the treatment of cancer.