Evaluation of the Repurposing Potential of Remdesivir for Non - Small Cell Lung Cancer : A Thesis Submitted to the Graduate School of Basic and Applied Sciences (BAS) Institute : Egypt-Japan University of Science and Technology (E-JUST) : In Partial Fulfilment of the Requirements for the Degree of Doctor of Philosophy in Biotechnology /
تقييم إمكانية إعادة استخدام عقار ريمديسيفير ضد سرطان الرئة ذي الخلايا غير الصغيرة : رسالة علمية مقدمة إلى المدرسة التخصصية للدراسات العليا - معهد العلوم الأساسية و التطبيقية : الجامعة المصرية اليابانية للعلوم و التكنولوجيا كاستيفاء جزئي لمتطلبات الحصول على درجة دكتوراه الفلسفة في التكنولوجيا الحيوية / إعداد هدير مجدي أحمد علي سودان ; لجنة الاشراف على الرسالة ا . م . د شریف حماد - أستاذ الكيمياء الطبية برنامج الصيدلة فارم دي - الجامعة المصرية اليابانية للعلوم و التكنولوجيا , أ . د . محمد غازي - أستاذ التكنولوجيا الحيوية - معهد العلوم الأساسية و التطبيقية - الجامعة المصرية اليابانية للعلوم و التكنولوجيا , أ . د . محمود سليمان - أستاذ الصيدلة و الصيدلة الصناعية - برنامج الصيدلة فارم دي - الجامعة المصرية اليابانية للعلوم و التكنولوجيا , أ . د. أحمد فتح الباب - أستاذ هندسة التصميم و التصنيع للأنظمة الكهروميكانيكية الدقيقة قسم الميكاترونيات و الروبوتات - كلية هندسة التصميم المبتكر - الجامعة المصرية اليابانية العلوم و التكنولوجيا ; لجنة المناقشة و الحكم على الرسالة أ . د . أماني أسامة كامل - استاذ الصيدلانيات و الصيدلة الصناعية بكلية الصيدلة - جامعة عين شمس , أ . د . عبدالهادي على عبدالوهاب - أستاذ بيولوجيا الأورام بالمعهد القومي للأورام , أ . م . د . شريف حماد - أستاذ الكيمياء الطبية - برنامج السيدلة قارم دي - الجامعة المصرية اليابانية للعلوم و التكنولوجيا , أ . د . محمد غازي - استاذ التكنولوجيا الحيوية - معهد العلوم الأساسية و التطبيقية - الجامعة المصرية اليابانية للعلوم و التكنولوجيا
by Hadeer Magdy Ahmed Ali Soudan ; Supervisor Committee Prof. Sherif Hammad - Professor of medicinal chemistry - PharmD Program - Egypt-Japan University of Science and Technology (E-JUST) , Prof. Mohamed Ghazy - Professor of medicinal chemistry - PharmD Program - Egypt-Japan University of Science and Technology (E-JUST) , Prof. Mahmoud Soliman - Professor of Pharmaceutics and Industrial Pharmacy - PharmD Program - E-JUST , Prof. Ahmed Fath El-Bab - Professor of Design and Manufacturing Engineering of Micro Electromechanical Systems (MEMS) - Mechatronics and Robotics Department - School of Innovative Design Engineering - E-JUST ; Examination Committer Prof. Amany Osama Kamel - Professor of Pharmaceutics and Industrial Pharmacy - Faculty of Pharmacy - Ain Shams University , Prof. Abdel Hady Ali Abdel Wahab - Professor of cancer biology - National cancer institute , Prof. Sherif Hammad - Professor of medicinal chemistry - PharmD Program - Egypt-Japan University of Science and Technology - (E-JUST) , Prof. Mohamed Ghazy - Professor of Biotechnology - Institute of Basic - and Applied Science (BAS) - E-JUST
- Alexandria : Hadeer Magdy Ahmed Ali Soudan 2024
- 90 leaves ; 30 cm
Includes a title page in Arabic
Thesis (Ph.D.)
Includes bibliographical references
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) comprising approximately 85% of cases. Regrettably, most NSCLC diagnoses occur at advanced stages (III or IV), where treatment options are largely limited to radiotherapy and chemotherapy Although patients initially respond to these treatments, drug resistance frequently emerges, diminishing long-term efficacy This highlights a critical need for novel therapeutics with enhanced efficacy and safety profiles. Drug repurposing has gained attention as an innovative approach that uses existing approved or investigational drugs to treat diseases beyond their original indications, reducing research costs and shortening development timelines. The known safety profiles and preclinical data of these drugs accelerate the approval process for new uses. In this context, remdesivir (RDV), a recently approved antiviral drug, was investigated for its potential anticancer activity against NSCLC cell lines. RDV targets viral RNA- dependent RNA polymerase (RdRP), which shares molecular and phylogenetic similarities with human telomerase reverse transcriptase (hTERT), the catalytic core of the telomerase enzyme This suggests RDV may serve as a promising inhibitor of telomerase activity in cancerous tissues RDV was loaded into biocompatible liposomes (RDV-Lips) composed of 1,2 dipalmitoyl - sn-glycero-3-phosphocholine (DPPC), cholesterol, and polyethylene glycol hexadecyl ether (Brij-58) to enhance its solubility and anticancer efficiency RDV-Lips were developed using thin-film hydration and then subjected to physicochemical characterizations. The selected formulations were evaluated for their stability, in vitro release, and in vitro anticancer activity The size range of RDV-Lips was 83.8-157.9 nm with a polydispersity index (PDI) lower than 0.23 and entrapment exceeded 93% Altering the cholesterol content of RDV-Lips offered a control point of RDV release, where increasing the concentration from 2.5% to 25% 10-fold) shifted the release profile from fast to slow release. RDV-Lips showed enhanced anticancer activity against A549 and H460 cells NSCLC cell lines, with selective toxicity toward cancer cells over normal human skin fibroblasts (HSF) cells. RDV-Lips inhibited colony formation, increased lipid peroxidation, induced apoptosis, and inhibited the telomerase activity in a dose-dependent manner. Moreover, in silico molecular docking analysis indicated that RDV binds to both viral RdRP and hTERT with comparable binding energies of -8.42 and -8.00 kcal/mol, respectively In conclusion, RDV Lips effectively overcame RDV's solubility limitations and enhanced its anticancer efficacy highlighting RDV's potential as a therapeutic against NSCLC. The anticancer effects likely result