Development of a new targeted liposomal delivery system of doxorubicin modified with lymphoma cell specific antibody

Download

index.pdf

Date

2014

Author

Dalgıç, Ali Deniz

Metadata

Show full item record

Item Usage Stats

79
views

31
downloads

Three doxorubicin loaded drug carrier systems were prepared against Lymphoma diseases. The first approach was to target DXR loaded liposomal system by attaching cell specific antibodies. Non-internalizing anti-CD20 antibody was used to target Namalwa cells and internalizing anti-CD30 antibody was used to target B lymphoma cells. Targeted DXR loaded liposomes were prepared and their cytotoxicity against Lymphoma cells were compared with untargeted DXR loaded liposomes. The targeted liposome formulations were optimized to have around “92” anti-CD20 and “31” anti-CD30 antibodies per single 100 nm sized liposome (HSPC:CHOL:DSPE-PEG; 2:1:0.2). After 48 hours of incubation with Namalwa cells, anti-CD20 targeted DXR loaded liposomes caused over 87% toxicity while untargeted liposomes resulted with 19% cell death. However, anti-CD30 targeted liposomes toxicity improvement compared to untargeted liposomes was not clear due to less number of targeting moieties/cell in the study. So, this system will be further optimized. A second study was performed to investigate possible doxorubicin cytotoxicity enhancement by calcitriol pretreatment on Namalwa cells. The combinational effect of both agents was investigated firstly by treating Namalwa cells with their free form. We showed that Namalwa cells are more susceptible to DXR after 72 hours of calcitriol pretreatment. Then both agents co-loaded to liposomes and cytotoxicity compared with only doxorubicin loaded liposomes. Calcitriol and DXR co-loading to liposome, enhances cytotoxicity with in a shorter time with lower concentrations. Both modified liposomal systems prepared successfully and caused improved toxicity relative to DXR loaded liposomes.

Subject Keywords

Lymphomas., Liposomes., Doxorubicin., Lymphocytes.

URI

http://etd.lib.metu.edu.tr/upload/12617994/index.pdf
https://hdl.handle.net/11511/24067

Collections

Graduate School of Natural and Applied Sciences, Thesis

Suggestions

OpenMETU
Core

Development of a novel zebrafish xenograft model in ache mutants using liver cancer cell lines Avci, M. Ender; Keskus, Ayse Gokce; Targen, Seniye; Isilak, M. Efe; Ozturk, Mehmet; Atalay, Rengül; ADAMS, MİCHELLE; KONU KARAKAYALI, ÖZLEN (2018-01-25) Acetylcholinesterase (AChE), an enzyme responsible for degradation of acetylcholine, has been identified as a prognostic marker in liver cancer. Although in vivo Ache tumorigenicity assays in mouse are present, no established liver cancer xenograft model in zebrafish using an ache mutant background exists. Herein, we developed an embryonic zebrafish xenograft model using epithelial (Hep3B) and mesenchymal (SKHep1) liver cancer cell lines in wild-type and achesb55 sibling mutant larvae after characterization...
Development of poly (I:C) modified doxorubicin loaded magnetic dendrimer nanoparticles for targeted combination therapy Khodadust, Rouhollah; Unsoy, Gozde; Gündüz, Ufuk (2014-10-01) The objective of this study was to develop and evaluate the anticancer activity and the safety of a combinational drug delivery system using polyamidoamine (PAMAM) dendrimer-coated iron oxide nanoparticles for doxorubicin and poly I:C delivery in vitro. Dendrimer-coated magnetic nanoparticles (DcMNPs) are suitable for drug delivery system as nanocarriers with their following properties, such as surface functional groups, symmetry perfection, internal cavities, nano-size and magnetization. These nanoparticle...
A microfluidic device enabling drug resistance analysis of leukemia cells via coupled dielectrophoretic detection and impedimetric counting Demircan Yalçın, Yağmur; Töral, Taylan Berkin; Sukas, Sertan; Yıldırım, Ender; Zorlu, Özge; Gündüz, Ufuk; Külah, Haluk (2021-12-01) We report the development of a lab-on-a-chip system, that facilitates coupled dielectrophoretic detection (DEP-D) and impedimetric counting (IM-C), for investigating drug resistance in K562 and CCRF-CEM leukemia cells without (immuno) labeling. Two IM-C units were placed upstream and downstream of the DEP-D unit for enumeration, respectively, before and after the cells were treated in DEP-D unit, where the difference in cell count gave the total number of trapped cells based on their DEP characteristics. Co...
INVESTIGATION OF CLONAL EVOLUTION IN CAPECITABINE RESISTANT CACO-2 AND IRINOTECAN RESISTANT HT-29 CELL LINES BY USING CELLULAR BARCODING TECHNOLOGY Danışık, Nurseda; Acar, Ahmet; Özen, Can; Department of Biotechnology (2022-10-31) The development of drug resistance in tumor cells is one of the biggest problems currently in the clinic. As the pace of drug discovery slows and each new drug becomes increasingly expensive to bring to market, it is becoming clearer that better model systems and an understanding of drug resistance mechanisms are needed for second-line therapies. The overall aim of this project is to investigate the clonal evolution and drug resistance in colorectal cancer cell lines Caco-2 and HT-29 by using cellular barco...
Design and characterization of capsaicin loaded nanoemulsions Akbaş, Elif; Öztop, Halil Mecit; Söyler, Ulviye Betül; Department of Food Engineering (2016) In recent years, nanoemulsion based systems have been successfully used in food, medical and pharmaceutical applications as effective lipophilic carrier systems for nutraceuticals, drugs, antioxidants and antimicrobial agents. The primary active ingredient of chili pepper, capsaicin is a hydrophobic substance and was proved to be a compound showing good antimicrobial activity against various microorganisms. The aim of the proposed study was to prepare and characterize capsaicin loaded nanoemulsion systems. ...

Citation Formats

A. D. Dalgıç, “Development of a new targeted liposomal delivery system of doxorubicin modified with lymphoma cell specific antibody,” M.S. - Master of Science, Middle East Technical University, 2014.