Enhanced drug carrier capacity after post modification process for amino acid substitute phosphazene based microspheres with anticancer activity

Abstract

In this study, drug carrier HCCP-PP-LEEMP microspheres were synthesized by using Hexachlorocyclotriphosphazene (HCCP), Phenolphthalein (PP) and l-Lysine Ethyl Ester Dihydrochloride (LEE) by polycondensation reaction. The synthesized spheres were modified in an acidic environment, and a cationic charge was formed on their surfaces. Synthesized and quaternized microspheres were characterized using FT-IR, SEM, TEM, TGA and Zeta (ζ) potentials analyzes. HCCP-PP-LEE-ATA-QMP microspheres with increased anionic drug carrying capacity as a result of quaternization were used as carriers for Sodium Diclofenac (NaDc) and Cimetidine drugs. While the unmodified HCCP-PP-LEEMP microspheres did not retain the NaDc drug, the NaDc drug retention capacity of the quaternized HCCP-PP-LEE-ATA-QMP microspheres was calculated as 99.6677 mg/g. Thus, it was determined that the drug holding capacity of the microspheres could be increased tens of times compared to their initial state, thanks to the positive charges formed on the surface of the drug carrier microspheres as a result of quaternization. At the same time, Cimetidine, a type of chemotherapeutic drug, was loaded into the microsphere using as drug delivery system. In vitro drug release behaviors of the developed phosphazene and amino acid-based delivery system were investigated and drug release kinetic models were determined. In addition, the antibacterial and antifungal effects of the microspheres were investigated with the effect of LEE in the structure of the microspheres. Then, the anticancer behavior of the cimetidine-loaded microspheres was tested on HT-29 colon cancer cell lines. Thus, a potential carrier system that can carry drugs for the treatment of a selective disease or chemotherapeutics for the treatment of cancer has been synthesized.