Synergistic Effect of Gemcitabine and Clofazimine in Co-loaded Liposomal Formulation for Multidrug Treatment Approach of Osteosarcoma

Date

2017-07-19

Author

Çalışkan, Yağmur
Güleç, Ezgi
Gerekçi, Selin
Tezcaner, Ayşen
Özen, Can
Keskin, Dilek

Metadata

Show full item record

Item Usage Stats

188
views

0
downloads

ntroduction: Osteosarcoma is the most common cancer in bone with high occurrence in children. The development of resistance is a challenge of current treatment strategies that needs to be improved with novel treatment strategies. In the current research, a new dual drug delivery system was developed with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposome formulations for osteosarcoma treatment. GEM is a pyrimidine antimetabolite that inhibits DNA synthesis and CLF is a leprostatic and anti-inflammatory drug that has been recently recognized as effective on cancer. Liposomal formulation of GEM and CLF was prepared using advantage of their specific localization in liposome; hydrophilic GEM being loaded into core and lipophilic CLF sequestering in hydrophobic lipid-bilayer. It is the first time that CLF is evaluated for its cytotoxicity on bone cancer cells and investigated for its synergistic effect with GEM on osteosarcoma. Methods: PEGylated liposomal formulations were prepared with DPPC:CHOL:DSPE-PEG (2000) lipids. They were investigated for their GEM and CLF encapsulation and loading efficiencies, in vitro release profiles, particle size, zeta potential and morphological properties. The cytotoxicity of liposome formulations were investigated by MTT assay on Saos-2 cells. Flow cytometry analyses were done to determine apoptotic effects of GEM, CLF and their co-loaded liposome groups on Saos-2 cells. Results: Characterization studies showed high encapsulation efficiency and loading of both GEM and CLF in liposome formulations. CLF release was enhanced while GEM release was slowed down in co-loaded formulations compared to their single loaded cases. Size of all liposomal formulations were under 200 nm and zeta potential values were slightly negative. All GEM/CLF co-loaded liposomal formulations showed significantly enhanced cytotoxicity than GEM loaded and CLF loaded liposome treatments. Use of CLF with GEM was found to have synergistic effect (CI<1) according to CompuSyn analysis. Results of flow cytometry experiments showed higher apoptotic cell ratio upon GEM/CLF co-loaded liposome treatments compared to other liposome treatment groups. Conclusion: Novel liposome formulation of GEM/CLF co-loaded liposome was successfully presented for the first time in this study. CLF’s single or co encapsulation with GEM into liposome was a new approach for enhancement of anticancer effect on Saos-2 cells. This formulation is thought to bring further advantages in terms of decreased side effects with the CLF contribution. It is also expected to provide specific therapeutic benefits of liposomal formulations. Therefore, GEM/CLF co-loaded liposomal delivery system is proposed to bring a novel approach for treatment of osteosarcoma.

URI

https://hdl.handle.net/11511/71198
https://crs.confex.com/crs/2017/meetingapp.cgi/Paper/3527

Conference Name

Controlled Release Society Annual Meeting and Exposition (2017)

Collections

Department of Engineering Sciences, Conference / Seminar

Suggestions

OpenMETU
Core

A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation Caliskan, Yagmur; Dalgıç, Ali Deniz; Gerekci, Selin; Gulec, Ezgi A.; Tezcaner, Ayşen; Özen, Can; Keskin, Dilek (2019-02-25) Osteosarcoma is the most common cancer in bone. Drug resistance is a challenge of current treatments that needs to be improved with novel treatment strategies. In this research, a new dual drug delivery system was developed with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposome formulations. GEM is a well-known anticancer agent and CLF is a leprostatic and anti-inflammatory drug recently recognized as effective on cancer. GEM and CLF co-loaded liposomal formulation was achieved with compartmentaliz...
Cancer modeling via biologically validated genes Karakelle, Barış Su; Purutçuoğlu Gazi, Vilda; Ürün, Yüksel (2017-05-10) The cancer disease is the second most common disease type seen after the frequency of the cardiovascular diseases. The frequency of this genetic disease changes with respect to the gender. Accordingly, the gynecological cancer, which covers ovarian, endometrial or cervical cancer, is the second most common cancer type in women after the breast cancer. Similar to other cancer types, the gynecological cancer is the system disease, meaning that the malfunctions and mutations in the gene regulatory ...
Analyses and modeling of ovarian cancer microarray data Karakelle, Barış S; Purutçuoğlu Gazi, Vilda; Department of Biomedical Engineering (2019) Ovarian cancer is one of the common cancer types among other oncological diseases. The major causes of this cancer can be listed as age, obesity, hormone therapy, material inheritance and contraceptive pills. Due to its generality and importance, many researches have been conducted from distinct labs about this illness and its plausible causes have been intensively investigated either inmicroarray studies, where just part of the related genes are detected, or in thepairwise correlation analyses between the ...
Network-based discovery of molecular targeted agent treatments in hepatocellular carcinoma Fayetörbay, Rumeys; Tunçbağ, Nurcan; Department of Bioinformatics (2020) Hepatocellular carcinoma (HCC) is one of the most-deadly cancers and the most common type of primary liver cancer. Multikinase inhibitor Sorafenib is one of FDA approved targeted agents in HCC treatment. PI3K/AKT/mTOR pathway is altered in about 51% of HCC; hence, understanding how Sorafenib and PI3K/AKT/mTOR pathway inhibitors act at signaling level is crucial for targeted therapies and to reveal the off-target effects. In this work, we use gene expression profiles (GEPs) of HCC cells (Huh7 and Mahlavu) wh...
Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer Hua, Serenus; Williams, Cynthia C.; Dimapasoc, Lauren M.; Ro, Grace S.; Özcan Kabasakal, Süreyya; Miyamoto, Suzanne; Lebrilla, Carlito B.; An, Hyun Joo; Leiserowitzf, Gary S. (Elsevier BV, 2013-03-01) Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we ana...

Citation Formats

Y. Çalışkan, E. Güleç, S. Gerekçi, A. Tezcaner, C. Özen, and D. Keskin, “Synergistic Effect of Gemcitabine and Clofazimine in Co-loaded Liposomal Formulation for Multidrug Treatment Approach of Osteosarcoma,” presented at the Controlled Release Society Annual Meeting and Exposition (2017), Boston, Amerika Birleşik Devletleri, 2017, Accessed: 00, 2021. [Online]. Available: https://hdl.handle.net/11511/71198.