Abstract:
Targeted drug delivery systems have gained much attention in recent years due to the fact that it offers useful solutions to the problems concerning chemotherapy drugs. The main aim in targeted drug delivery is to transport the chemotherapy agent directly to the cancer tissue without having side effects on the healthy tissues, with the help of nanocarriers. Also the bioavailability of the drugs are increased with nanocarriers. Polymeric nanoparticles are one of these nanocarriers. The reasons to choose polymeric nanoparticles among other nanocarriers are that they are easily produced, provide high drug encapsulation efficiency and stable enough to investigate their effects in vitro. In this study, first generation nanoparticles were prepared with PLA as a building block. Anticancer drug doxorubicin was physically loaded into hydrophobic core of the nanoparticles. To increase the drug loading efficiency, the drug molecules were conjugated to polymer chains of the nanoparticle by means of Diels-Alder reaction. To achieve this, furan-bearing PLA-carbonate copolymer was synhesized via ring opening polymerization, as a building block of the nanoparticles, whereas the drug molecules were modified with maleimide linker, EMCH. To enhance drug release profiles of the nanoparticles, mono-maleimide PEG chains were synthesized to conjugate to them via Diels-Alder reaction and second generation nanoparticles were produced. Finally, cRGDfK-maleimide molecules were attached to the PEG-PLA nanoparticles for active targeting also with Diels-Alder reaction and third generation nanoparticles were generated.
