Development of gemcitabine and clofazimine coloaded liposomal delivery system for osteosarcom treatment

Çalışkan, Yağmur
New strategies for more effective treatments need to be developed to cure osteosarcoma patients. Current study was designed to produce a dual drug delivery system with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposomes against osteosarcoma diseases. GEM is a second line therapy for osteosarcoma and with combinational use of another regimen it could be much more effective. CLF, an antimycobacterial agent, has been recently recognized as effective on cancer treatment and it was suggested to act on osteosarcoma disease since Wnt signaling pathway is one of the pathway that CLF affects. To prevent the increased toxicities of both agents and control their biodistribution, they were encapsulated into PEGylated liposome. The liposomes were produced in sizes to be administered intravenously (D: 100-150 nm). With the small size of liposomes the tumor cells could be targeted passively by the liposomal system via enhanced permeation and retention effect. Liposomal formulations showed high GEM and CLF loading capacities (90.1±1.16 and 80.1±1.45) and very slow release of GEM and CLF was observed. The cytotoxicity of liposomal formulations were investigated by MTT test and toxicity improvement was observed for co-loaded liposomes compared with single agent loaded liposomes after 24 h incubation with Saos-2 cells. Free drugs treated groups showed higher cytotoxicities than the liposomal formulations. Flow cytometry results were similar; there were more cells in apoptotic stage in GEM/CLF combinational groups (both free and liposomal formulations) than single agent groups and toxicity of GEM/CLF co-loaded liposomal formulation was numerically lower than the free GEM/CLF group. Cell cycle analysis indicates accumulation of cell population at G0/G1 phase was high when treated with liposomes co-loaded with GEM and CLF. GEM and CLF had apoptotic effects on Saos-2 cells as mitochondrial membrane depolarized cells’ ratio increased. Caspase-3 positive cells and early apoptotic cells percentage was increased compared to untreated groups at 24 h. GEM showed a synergistic effect with CLF on Saos-2 cells. With these results, it can be suggested liposomal formulation co-loaded with GEM and CLF would have potential for treating osteosarcoma. 


Peptide-based drug systems /
Parlak, Melek; Özçubukçu, Salih; Department of Chemistry (2017)
The increasing appeal of safe, cheap and effective treatments against various type of diseases has paved the way for the discovery and development of innovative peptide-based drug and drug delivery systems. The relative ease with which peptide based-materials can be synthesized and the wide range of synthetic techniques available have ensured that these materials can be tuned to adopt specific conformation or modified to contain specific functional groups. Our major focus in this thesis is developing peptid...
Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery
ÜNSOY, GÖZDE; Khodadust, Rouhollah; Yalcin, Serap; Mutlu, Pelin; Gündüz, Ufuk (2014-10-01)
Targeted drug delivery is a promising alternative to overcome the limitations of classical chemotherapy. In an ideal targeted drug delivery system carrier nanoparticles would be directed to the tumor tissue and selectively release therapeutic molecules. As a novel approach, chitosan coated magnetic nanoparticles (CS MNPs) maintain a pH dependent drug delivery which provides targeting of drugs to the tumor site under a magnetic field. Among various materials, chitosan has a great importance as a pH sensitive...
Synthesis and characterization of fatty acid based hyperbranched polymers for anti-cancer drug delivery
Güç, Esra; Gündüz, Ufuk; Department of Biology (2008)
Conventional methods of chemotherapy requires novel therapy systems due to serious side effects and inefficiency of drug administration. In recent years many studies are carried out to improve drug delivery systems. Polymers are one of the most important elements for drug delivery research due to their versatility. By the discovery of dendritic polymers, drug delivery studies gained a new vision. Highly branched monodisperse structure, multiple sites of attachment, well-defined size and controllable physica...
Development and characterization of cortisone derivative drugcarrying polymeric microspheres
Öcal, Yiğit; Keskin, Dilek; Özen, Seza; Department of Biomedical Engineering (2011)
In this study, it is aimed to develop an injectable controlled release system of PCL and P(L,DL)LA microspheres loaded with TA and/or Ral for local treatment of rheumatoid arthritis which will avoid from systemic side effects of traditional administration and eliminate problems caused by direct local injections. Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disorder that most commonly causes inflammation and tissue damage in joints and tendon sheaths. Current strategies for the disease are ma...
Characterization and Evaluation of Triamcinolone, Raloxifene, and Their Dual-Loaded Microspheres as Prospective Local Treatment System in Rheumatic Rat Joints
Ocal, Yigit; Kurum, Baris; Karahan, Siyami; Tezcaner, Ayşen; Ozen, Seza; Keskin, Dilek (Elsevier BV, 2014-8)
In this study, injectable microspheres were developed for the local treatment of joint degeneration in rheumatoid arthritis (RA). Microspheres loaded with triamcinolone (TA), a corticosteroid drug, and/or raloxifene (Ral), a cartilage regenerative drug, were prepared with a biodegradable and biocompatible polymer, polycaprolactone (PCL). Microspheres were optimized for particle size, structural properties, drug release, and loading properties. In vitro release of Ral was very slow because of the low solubil...
Citation Formats
Y. Çalışkan, “Development of gemcitabine and clofazimine coloaded liposomal delivery system for osteosarcom treatment,” M.S. - Master of Science, Middle East Technical University, 2016.