Abstract

Carboplatin's success in the treatment of major types of cancer has been attributed to its ease of administration and its high therapeutic index. However, despite its superior toxicity profile, myelosuppression remains to be its dose-limiting side effect. Liposomes have been researched extensively as carrier systems for therapeutic agents; their high biocompatibility, their ability to escape the immune system and most importantly their ability to incorporate both hydrophobic and hydrophilic drugs led to numerous liposomal formulations being designed for cancer therapy. Magnetic nanoparticles have been gaining attention as their properties enable them to be used in various therapeutic and diagnostic applications, in addition to gene and drug delivery. We report the successful preparation of magnetic liposomal formulation with particle size less than 200 nm, coated with Polyethylene Glycol, encapsulating superparamagnetic magnetite nanoparticles and carboplatin in its aqueous lumen. Two types of liposomes were prepared through thin film hydration technique; magnetite liposome and carboplatin-magnetite liposome with mean particle sizes of 183.3 ± 2.65 nm and 192.5 ± 3.42 nm respectively. Both formulations showed uniform particle size distribution and sterical stability as evident from their polydispersity index and Zeta-potential values. Encapsulation efficiency of magnetite in magnetite liposomal formulation was 61.37%, this value decreased significantly upon incorporation of carboplatin with magnetite in the second formulation. Carboplatin's EE% was found to be 13.87%, its release profile from the liposome showed a controlled release over the course of 72 hours. The prepared formulations have been successfully magnetically controlled with optimized magnetic gradient and input current strength. Additionally, in vitro tests performed on melanoma, mammary and oral squamous cell carcinoma cell lines showed significant superior cytotoxicity profile of carboplatin-magnetite liposome over free carboplatin solution.

School

School of Sciences and Engineering

Department

Chemistry Department

Degree Name

MS in Chemistry

Graduation Date

Fall 12-17-2019

Submission Date

12-17-2019

First Advisor

Shoeib, Tamer

Committee Member 1

El Guendy, Nadia

Committee Member 2

Abdel Naser, Anwar

Extent

79 p.

Document Type

Master's Thesis

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy. The author has granted the American University in Cairo or its agents a non-exclusive license to archive this thesis, dissertation, paper, or record of study, and to make it accessible, in whole or in part, in all forms of media, now or hereafter known.

Institutional Review Board (IRB) Approval

Not necessary for this item

Comments

First and foremost, I thank God for granting me the strength and perseverance to finish this project. None of this would've been possible without the guidance of my thesis supervisor Dr. Tamer Shoeib, whose continuous support, patience and encouragement helped me throughout my thesis work and for this I'm in deep gratitude for him. I'd like to thank Dr. Islam Shoukry and the colleagues in the medical MNR lab in the German University in Cairo, especially Seif Gaballah for facilitating conducting the magnetic control experiments. Also, I'd like to thank Dr. Nashwa El Khazragy and Global labs for facilitating conducting the cytotoxicity experiments. I'd like to acknowledge financial support provided to me by the American University in Cairo through its university fellowship which enabled me to complete my master's degree. My thanks also go to the staff of the Chemistry Department for helping throughout my project. I'm particularly grateful for Ahmed Omia for continuously supporting me and generously dedicating his time for helping me throughout my thesis work. I'm grateful for my dear friends Mai Gamal, Engy Magdy, Sherry El Shabassy and Dina Maziunah who always empowered me and provided me with all kinds of support throughout this journey. Finally, I'm thankful for my mother, my role model who I always look up to, my father for believing in me and pushing me forward, and for my brother Ahmed for always being there for me whenever I needed him. Everything that I achieved wouldn't have been possible without their motivation, support and continuous prayers. I'm genuinely thankful for my husband Ismail for his love, support and encouragement at all times, and for my daughter Layla who is the main reason for me to always work harder and be the best version of myself.

Creative Commons License

Creative Commons Attribution-No Derivative Works 4.0 International License
This work is licensed under a Creative Commons Attribution-No Derivative Works 4.0 International License.

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