A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation

Date

2019-02-25

Author

Caliskan, Yagmur
Dalgıç, Ali Deniz
Gerekci, Selin
Gulec, Ezgi A.
Tezcaner, Ayşen
Özen, Can
Keskin, Dilek

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

230
views

0
downloads

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 compartmentalization as hydrophilic GEM being in core and lipophilic CLF sequestering in lipid-bilayer. Liposomes had high encapsulation efficiency (above 90%, GEM and above 80%, CLF). CLF release was enhanced while GEM release was slowed down in coloaded liposomes compared to single cases. GEM/CLF co-loaded liposomes significantly enhanced cytotoxicity than GEM or CLF loaded liposomes on osteosarcoma cell line. CLF and GEM had synergistic effect (CI < 1). Results of flow cytometry showed higher apoptotic cell ratio, caspase-3 activity, mitochondrial membrane depolarized cells' ratio for GEM/CLF co-loaded liposome treatments than other liposomes. Cytotoxicity of CLF on bone cancer cells and also its synergistic effect with GEM on osteosarcoma is reported for the first time with this study. CLF's loading with GEM into liposome was also a new approach for enhancement of anticancer effect on Saos-2 cells. Therefore, GEM/CLF co-loaded liposomal delivery system is proposed as a novel approach for treatment of osteosarcoma.

Subject Keywords

Clofazimine, Gemcitabine, Co-loading, Liposome, Osteosarcoma, Multi-drug delivery

URI

https://hdl.handle.net/11511/30308

Journal

INTERNATIONAL JOURNAL OF PHARMACEUTICS

DOI

https://doi.org/10.1016/j.ijpharm.2018.12.041

Collections

Graduate School of Natural and Applied Sciences, Article

Suggestions

OpenMETU
Core

Synergistic Effect of Gemcitabine and Clofazimine in Co-loaded Liposomal Formulation for Multidrug Treatment Approach of Osteosarcoma Çalışkan, Yağmur; Güleç, Ezgi; Gerekçi, Selin; Tezcaner, Ayşen; Özen, Can; Keskin, Dilek (2017-07-19) 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-inflammat...
Bioinformatic prediction and coexpression network identifies repurposed novel drugs for papillary thyroid cancer Temiz, Kubra (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10) Thyroid cancer is a type of cancer that affects the endocrine system and has a high malignancy. Papillary thyroid cancer, the most common subtype of thyroid cancer, also has well-differentiated features. Early diagnosed and well-differentiated thyroid cancer is generally associated with a good prognosis and/or survival rate. Therefore, it is of great importance to determine the molecular signatures of the disease. In this study, five papillary thyroid cancer-related gene expression datasets were analyzed us...
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...
PEI – starch nanoparticles for cancer gene therapy Kandemir, Berke Bilgenur; Hasırcı, Vasıf Nejat; Aşçıoğlu Öz, Gamze; Department of Biotechnology (2013) Cancer is the most serious disease of in this century and death rates due cancer are increasing rapidly. Since the conventional cancer treatment techniques like chemotherapy, radiation therapy and surgical operations are not sufficiently efficient and they even are harmful for healthy tissues, there is an urgent need for effective treatment techniques with minimal or no side effects. Controlled drug delivery systems are offered as an alternative approach to cancer therapy that helps prevent excessive drug u...
Targeted co-delivery of doxorubicin and TPGS to breast cancer cells by PLGA coated magnetic nanoparticles Metin, Esra; Gündüz, Ufuk; Mutlu, Pelin; Department of Biotechnology (2017) Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells also effect as cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks.The targeting strategy can be changed depending on carrier types, but magnetic nanoparticles are commonly preferred due to their easy targetable features by using ext...

Citation Formats

Y. Caliskan et al., “A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation,” INTERNATIONAL JOURNAL OF PHARMACEUTICS, pp. 97–104, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30308.