GC-14. CaCO3 dextran sulfate-coated vaterites as a system for regional doxorubicin administration
Natalia N. Sudareva1,2, Olga M. Suvorova1, Dmitry N. Suslov3, Oleg V. Galibin2, Alexander D. Vilesov1,2
1 Institute of Macromolecular Compounds, Russian Academy of Sciences, St. Petersburg, Russia
2 RM Gorbacheva Research
Institute, Pavlov University, St. Petersburg, Russia
3 A. M. Granov Russian Research Center of Radiology and Surgical Technologies, St. Petersburg, Russia
Correspondence:
Dr. Natalia N. Sudareva, phone:+7 (921) 921-35-65, e-mail: nnsas@mail.ru
Summary
Doxorubicin (DOX) is a water-soluble anthracycline antibiotic with high anti-cancer efficacy. Reducing the concentration of DOX in the blood below the cardiotoxic level during therapy can be achieved by forming a depot containing DOX delivery systems with prolonged drug release. For these purposes, calcium carbonate porous vaterites coated with polyanion dextran sulfate (DexS) were used. The submicron size of the carriers does not allow them to be freely included in the bloodstream. The toxic drug spreads through the body only after it enters the blood as a result of release from the delivery systems (DS). Intraperitoneal administration of DOX-containing DS to rats with transplanted Seidel’s hepatoma allowed us to evaluate the effective concentration of DOX, which inhibits tumor growth and reduces the volume of ascitic fluid.
Methods and results
The dynamics of DOX intake into the blood of healthy rats after intraperitoneal administration of DOX in DS based on submicron DexS-coated porous CaCO3 cores was determined by HPLC. The reaction of experimental rats with Seidel’s hepatoma inoculated within 21 days after DS administration was controlled on the basis of physical examination results, as well as autopsy of rats.
Results
It was shown that intraperitoneal administration of 2 mg of DOX in a DS in rats increases the life expectancy by 1.75 times and reduces the volume of ascites in experimental animals by half. A more effective suppression of the tumor can be expected by increasing the dose of DOX to 4 mg per animal. The dynamics of the appearance of DOX in blood plasma after intraperitoneal administration of the drug in DS to healthy rats was compared with free DOX dynamics. 2 days after the administration of free DOX to rats, it disappears from the blood plasma. As can be seen from Figure 1, the use of DS allows us to prolong the presence of the drug in the blood. Porous carbonate cores coated with dextran sulfate showed DOX release at theconcentrations below cardiotoxic within two weeks.
Figure 1. DOX concentrations in rats’ plasma after intraperitoneal administration. 1 – free DOX; 2 – CaCO3+DexS+DOX
Conclusion
No negative reactions were detected in rats using DS, which was confirmed by the behavior and physical condition of the experimental animals, as well as the results of autopsy. Therefore, the studied DS based on CaCO3 carbonate cores coated by DexS can be used for prolonged regional delivery of the DOX antitumor drug.
Keywords
Doxorubicin, drug delivery system, CaCO3, dextran sulfate, Seidel’s hepatoma.
