Doxycyline solution, liposome and nanoparticle formulations with sodium taurocholate and determination of transport properties through Caco-2 cell line


YÜCEL Ç., Değim Z., Yılmaz Ş.

“International Multidisciplinary Symposium on Drug Research and Development - New Drug Entities & Cancer Research, Nanotechnology & Scientific and Industrial Perspectives, Türkiye, 1 - 04 Kasım 2013, ss.91

  • Yayın Türü: Bildiri / Tam Metin Bildiri
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.91
  • Erciyes Üniversitesi Adresli: Evet

Özet

Doxycycline belongs to the family of tetracycline antibiotics and inhibits bacterial protein synthesis. Matrix metalloproteinases (MMPs) enzymes play pivotal roles in the metastatic process of cancers. MMP-2, degrade components of basement membrane and they are believed to be crucial in the process of invasion by malignant tumors1. Doxycycline is an effective inhibitor of cell proliferation, migration, and MMP activity2. Based on the secretion of MMP-2 from cancer cells, various formulations containing MMP inhibitor, doxycycline, have been tested in this study. In this study, Caco-2 cells were used as a model that are human colon cancer derived cells. They are increasingly used in membrane transport studies3,4. Initially, MTT test was performed to test the effect of doxycycline and sodium taurocholate (NaTC, absorption enhancer) on the viability of Caco-2 cells. According to the MTT test results, doxycycline and NaTC concentration did not exceed to 10 µg/mL and 1.875 mM for 24 hours of transport period. The cumulative amount of doxycycline and NaTC solution, nanoparticle and liposome formulations transported through apical to basolateral side of Caco-2 cells was found to be 85.5%, 53.4% and 68.4% (n=3) for doxycycline respectively. Apparent permeability coefficients (k) were calculated as 1.08±0.34, 2.13±0.09 and 5.83±0.07 (n=3) for doxycycline solution, nanoparticle and liposome formulations respectively. For MMP-2 inhibition, the growth of the cancer cells were inhibited by the developed doxycycline formulations and NaTC liposomes showed the best inhibition percentage with 95.1±0.002 % significantly (n=4)5. This suggests that liposome formulation may be more effective and it can be used for the prevention of metastatic cancer cells.