Meme Kanseri için Hedeflenebilir İlaç Salım Sistemi Olarak İkili İlaç Yüklü Albümin Bazlı Nanopartiküllerin Geliştirilmesi

Abstract

Current areas of research in cancer include the development of carriers to allow alternative dosage routes, new therapeutic targets such as blood vessels that feed tumor growth, and more specific targeted therapies. An ideal drug delivery system should have optimal physical-chemical properties such as enhanced targeting ability, low toxicity and controlled drug release profile. Within the scope of this thesis, different albumin-based drug carrier formulations in the nano-size range have been prepared especially for breast cancer. Protein-polymer hybrid nanoparticles in the structure of poly(lactic-co-glycolic acid):albumin core-shell were synthesized based on nanoprecipitation method and particle size and size distribution were optimized. Active and passive targeting approaches are predominantly studied in current cancer therapy research. All synthesized particle formulations are suitable for passive targeting by trying to keep the targeted size in the range of 100-200nm, and formulations suitable for active targeting have been prepared by taking advantage of the albumin layer conjugated to the surface of the formulation, albumin being a nitrogen and energy source in the body, allowing the encapsulation of a second drug, and accumulating in tumor areas. In poly(lactic-coglycolic acid):albumin protein-polymer hybrid nanoparticles, Docetaxel, a chemotherapeutic active ingredient, was encapsulated in the core of the poly(lactic-coglycolic acid) and curcumin, a chemosensitizing and chemopreventive active ingredient, was encapsulated in the albumin layer forming the shell. In current studies carried out for the treatment of breast cancer, studies showing the importance of the combined use of Docetaxel and Curcumin in order to overcome drug resistance, to increase cell apoptosis by creating a synergistic effect, and to increase the effectiveness of treatment by sensitizing cells to chemotherapy. In addition to protein-polymer hybrid nanoparticles in the structure of Poly(lactic-co-glycolic acid):albumin core-shell synthesized for this purpose, nanoparticle formulations of both polymer and protein alone were also prepared. In this way, it was possible to compare both polymer-protein hybrid and protein nanoparticles in terms of size, charge, drug release, etc. On the other hand, the surface of the prepared formulations was conjugated with folic acid and thus synthesis, characterization and drug release studies of formulations suitable for specific targeting of cancer cells carrying folate receptors were carried out. For the synthesized formulations, characterization studies such as size analysis and zeta potential measurements with Zetasizer, SEM, FTIR, TGA, DSC, XRD, contact angle measurements were carried out. The encapsulation efficiencies and loading capacity values of the drug-loaded formulations were calculated, both single and dual in vitro drug release studies were investigated by dialysis method at 37oC in pH 5.6 PBS buffer media simulating acidic tumor microenvironment and pH 7.4 PBS buffer media simulating physiological blood, and compliance with different drug release kinetic models (Zero Order, First Order, Higuchi, Hixson-Crowell and Korsmeyer-Peppas) was examined.