Research Information System
Thesis Type: Doctorate
Institution Of The Thesis: Hacettepe University, Sağlık Bilimleri Enstitüsü, Radyofarmasi A.B.D., Turkey
Approval Date: 2019
Thesis Language: Turkish
Student: MERVE KARPUZ
Principal Supervisor (For Co-Supervisor Theses): Mine Silindir Günay
Supervisor: Asuman Yekta Özer
Abstract:
Overall, cancer is a fundamental health issue all around
the world. In particular, lung cancer is the type that has the highest
incidence and mortality rate. Although several methods including chest x-rays,
computed tomography, magnetic resonance and nuclear imaging methods are routinely
employed in the diagnosis and imaging of lung cancer; these techniques fall
short of sufficient when it comes to early diagnosis. On the other hand, the
most frequently used treatment methods for lung cancer are surgery,
radiotherapy and chemotherapy. Among these, surgery is the most effective
method in treating lung cancer; however, it can only be practiced in the early
stages of the disease. While radiotherapy is the treatment method of choice for
the patients with early-stage lung cancer that’s not suitable for surgical
procedures; chemotherapy is utilized in the treatment of advanced-stage
patients. The fact that chemotherapeutic
drugs are not tumor-specific and cause serious, systemic, toxic effects
constitutes one of the biggest problems in the treatment. Combination therapy,
is frequently used in cancer treatment, has various advantages including
reducing of toxic effects of monotherapy and targeting of different mechanisms.
Taking these facts into consideration, in our study;
nanosized liposome formulations were prepared. While doing so; paclitaxel was
encapsulated in the lipid bilayer and vinorelbin was encapsulated in the
hydrophilic core of the same liposomes. These formulations were targeted
actively and/or passively at the folate receptors in the non-small cell lung cancer
cells and labelled with 99mTc radionuclide. In the subsequent
characterization studies, the suitability of the profiles of liposomes for in
vitro studies has been proven by their particle size (about 150nm for passive
targeted ones and about 180 nm for active targeted ones) and encapsulation
efficiency of 15% for PCX and 20% for VNB as well as their zeta potential of
about -10 mV. The results of the stability studies showed that the liposome
formulations remained stable in tightly sealed containers for about 45 days at
4oC. The cytotoxicity profiles of these liposome formulations and
the results of the in vitro uptake studies were evaluated in the A549, H1299
and LLC-1 cell lines. According to the results of flow cytometry and MTT
analyses, liposomes were uptaken and showed high cytotoxic effects in cells.
By the results of biodistribution studies performed in
mice bearing lung cancer, radiolabeled with 99mTc, actively folate
targeted, co-drug encapsulated liposomes formulations were uptaken in tumuor
tissue compared to non-actively targeted one. In addition, the treatment
efficiency of actively folate targeted, co-drug encapsulated liposomes
formulations were found as higher than free drug combination and no-drug
encapsulated liposome formulation as control group. Furthermore, liposomal
formulations showed lower toxicity compared to free drug combinations in the
toxicity study considering body weight.