TOXICITY ASSESSMENT OF MONTMORILLONITE AS A DRUG CARRIER FOR PHARMACEUTICAL APPLICATIONS: YEAST AND RATS MODEL

Our previous study indicated that montmorillonite (MMT for short) was pharmaceutically feasible to be used as a carrier of an anticancer drug 5-FU. Emphasis of this study is thus placed on the toxicity of MMT to address whether it is clinically safe for practical use. Hematological data of rats model showed that the rats administered with oral MMT had significant increases in hemoglobin (Hb) concentration, Hamatocrit and RBC count than those of oral PBS buffer (p<0.05). However, MCV, MCH, MCHC, WBC Count and WBC were not statistically significant different between experimental and control group (p>0.05). Hematological analysis for intravenous injection also showed no statistically significant differences between experimental and control group (p> 0.05). Biochemical analysis pointed out that compared to oral PBS there was not only a significant decrease of sodium (Na+) and chloride (Cl-) ion (p< 0.05) in plasma for oral MMT, but also an extremely significant decrease in the plasma calcium (Ca2+) (p< 0.01). On the other hand, after intravenous injection of MMT compared to control group, a significant increase (p< 0.05) in ALT (SGPT), and an extremely significant decease (p< 0.01) in plasma potassium (K+) were observed. It is deserved to mention here that histochemical examinations were all normal, suggesting that montmorillonite may be considered non-toxic. Regarding histopathological sections of rats, there were all in normal ranges irrespective of experimental or control group. For bacterial model, a generally considered safe and non-pathological microorganism Saccharomyces cerevisiae was used as the model yeast to be administrated with various extracellular doses of MMT, montmorillonite-K6Fe(CN)(3) (MMTK), or montmorillonite-K6Fe(CN)(3)-sodium alginate (MMTK-SA) for toxicological assessments. Dose-response analysis indicated that the toxicity ranking as Lannate >> MMTK > MMTK-SA >> MMT-SA > MMT according to EC0 or EC50 line. These all suggested that MMT alone is much less toxic than Lannate and potassium hexacyanoferrate(III). Apparently, it was concluded that MMT alone could be considered non-toxic to S. cerevisiae and Wistar rat for myriads of applications.