Poli (Laktik-Ko-Glikolik Asit)-Kitosan Çekirdek/Kabuk Nanopartikullerden Kemopreventif ve Kemoterapötik Özellikteki Piperin ve Epigallokateşin Gallat’ın Sıralı Salımının İncelenmesi
Özet
Cancer is a disease that often results in death. In conventional treatment methods (such as surgery, chemotherapy, radiotherapy), the quality of life of the patient decreases intensely due to its side effects. In recent years, new methods for cancer treatment have been studied in increasing research. One of these new methods is polymeric nanoparticle drug delivery systems, which protect healthy cells and allow controlled drug release that only affects the tumor area. As a medicine, phytochemicals with various advantages are preferred instead of conventional drugs, allowing the reduction of side effects. In this thesis, poly(lactic-co-glycolic acid) PLGA nanoparticles were synthesized and coated with chitosan (KTS). Piperine (PIP) and epigallocatechin gallate (EGCG) are two compounds with phytochemical properties. There are studies showing that these two herbal-based chemopreventive-chemotherapeutic active substances can be used effectively in cancer treatment. It is aimed to increase their bioavailability by creating a synergistic effect when used together. In this direction, core-shell nanocomposite structure was formed by loading PIP on PLGA nanoparticles and coating with EGCG loaded KTS. Accordingly, PLGA nanoparticles (PLGA NPs), KTS coated PLGA nanoparticles (KTS-PLGA NPs), PIP loaded PLGA nanoparticles (PIP-PLGA NPs), KTS coated PIP loaded PLGA nanoparticles (PIP-PLGA-KTS NPs) and finally EGCG loaded KTS coated PIP loaded PLGA nanoparticles (KTS-PIP NPs) synthesized and characterization studies were carried out. Characterization studies were performed using ZetaSizer, FT-IR, DSC and SEM. The encapsulation efficiencies and loading capacities of PIP to PLGA nanoparticles alone and of PIP to PLGA nanoparticles coated with KTS alone were found as functions of the components that make up the composite structure and the amount of PIP. Then, the encapsulation efficiencies and loading capacities of both active substances were found in the nanocomposite structure, where EGCG was loaded into KTS and PLGA nanoparticles loaded with PIP were together. Thus, the most suitable EGCG-KTS-PIP-PLGA nanoparticle structure was determined in the presence of both active ingredients. PIP release from PLGA nanoparticles alone, PIP release from PLGA nanoparticles coated with chitosan were performed in vitro at pH 7.0 simulating blood for circulation in the body and pH 5.5 simulating tumor microenvironment for cancer cells. The release of EGCG and PIP from the most suitable EGCG-KTS-PIP-PLGA nanocomposite structure with PIP and EGCG together was investigated in vitro. The compatibility of the in vitro release profiles of each system described above with zero-order, first-order, Higuchi, Korsmeyer-Peppas, Hixson-Crowell kinetic models was examined, the values of the kinetic constants were calculated, and the release mechanism was proposed.
