Search In this Thesis
   Search In this Thesis  
العنوان
Evaluation of the use of paclitaxel loaded liposomes in combination with epigallocatechin-3-gallate for Michigan cancer foundation-7 breast cancer treatment: In vitro Study /
المؤلف
Ibrahim, Hagar Ahmed Hassanein.
هيئة الاعداد
باحث / هاجر احمد حسنين ابراهيم
مشرف / ثناء إبراهيم شلبي
مشرف / نيفان محمود فكرى
مناقش / منى ابراهيم شحاتة مصطفى
مناقش / يسرا شعبان ربيع النجار
الموضوع
Medical Biophysics. Biophysics.
تاريخ النشر
2022.
عدد الصفحات
84 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الفيزياء وعلم الفلك
تاريخ الإجازة
15/6/2022
مكان الإجازة
جامعة الاسكندريه - معهد البحوث الطبية - Medical Biophysics
الفهرس
Only 14 pages are availabe for public view

from 84

from 84

Abstract

The development of drug-loaded nanoparticles has boosted the effectiveness of anticancer drugs against a variety of cancer types as well as malignancies that are resistant to treatment. Nano formulation of water-insoluble pharmaceuticals has been identified and used to build drug delivery systems have the ability to enhance therapeutic index, minimizing the associated negative effects of the organic solvents it contains, and thereby increasing cancer cell responsiveness Palumbo et al., (1122).
Paclitaxel is one of the most successful medications for treating breast cancer, but it comes with substantial side effects and the risk of exposing normal tissues to free drug. As a result, an effective drug delivery system capable of delivering paclitaxel into tumor cells is required. Liposomes are an appealing alternative for this application because they are biocompatible and can accommodate both hydrophilic and lipophilic medicines.
Green tea’s chemo preventive advantages were connected to polyphenolic compounds, which are powerful antioxidants. EGCG is a significant active element in terms of cancer chemo preventive potential among the various polyphenolic chemicals identified from green tea. To increase the effectiveness of the therapy, paclitaxel encapsulated Nano liposomes can be combined with EGCG to improve the uptake of the tumor cells to the liposomes.
The study’s goal was to see if paclitaxel-encapsulated Nano liposomes and EGCG, a naturally occurring anticancer drug, had any therapeutic effect on MCF7 breast cancer cells. Cell viability and apoptosis were used to assess the potential treatment effectiveness.
GSH, caspas1, LDH, and DNA fragmentation were used to measure the apoptotic effect.
Paclitaxel was used in three forms, including free PTX, PTX Nano formulated with liposomes as a carrier, and PTX Nano formulated with liposomes as a carrier with EGCG to achieve these objectives.
A physical characterization of the PTX-NPs was carried out, including the determination of the nanoparticle size and surface charge, as well as the drug loading efficiency. In order to conduct the study, used MCF-7 cell lines.
Liposomal PTX was combined with a set concentration of EGCG. To determine the cytotoxic effect of various treatment modalities, a number of different experimental protocols were used.
The paclitaxel-loaded liposomes were developed on top of the improved formulation, which had a zeta potential of ” " ~ " ” -11 mV and a size of ” " ~ " ” 111 nm.
The bilayer of liposomes must be loaded with paclitaxel and the encapsulated medicine must be retained in the bilayer for long-term stability.
Paclitaxel loading was increased by optimizing the liposomal recipe for preparation.
FT-IR spectroscopy confirmed that PTX was properly conjugated with Nano liposomes.
The encapsulation efficiency was 919.
PTX had an IC51 of 211 micrograms per millilitre in cells of breast cancer MCF-7, Lip-PTX had an IC51 of 71 micrograms per milliliter, while EGCG with Lip-PTX had an IC51 of 11 micrograms per millilitre, showing that the combination effect of these two agents was much greater than that of Lip-PTX alone.
Summary, Conclusion & Recommendation
55
II- Conclusion
- When compared to PTX treatment alone, our treatment combination revealed significantly enhanced tumor cytotoxicity, and implementation of this treatment would allow for equivalent cancer cell death with lower PTX dosages, resulting in better adherence to dosing regimens and a reduction in adverse events.
- These investigations found that delivering liposomal preparation of paclitaxel could be a promising technique for improving its chemotherapeutic effectiveness while eliminating the adverse reactions linked to Cremophor EL.
- The study found that treating breast cancer cells with liposomal PTX and EGCG together increased the drug’s anticancer activity, with IC51 values indicating that the combined treatment was lower values than PTX-NPs alone.
- As a result, our findings suggest that EGCG combined with Lip-PTX has significant potential as a tumor-targeting and potent anticancer treatment that avoids the adverse effects of standard paclitaxel treatment while lowering the required lethal dose by sensitizing MCF7 cells to the chemotherapy.
- Treatment with EGCG boosted paclitaxel-induced cell death and enhance the efficiency of paclitaxel therapy in vitro, according to this study. As a result, we provide an alternate method for boosting paclitaxel sensitivity in breast cancer cells.
- This research could pave the way for the application of delivery systems via nanoparticles that degrade and are safe for the body to boost chemo preventive drug bioavailability, solubility, stability, and payload.
III- Recommendation
- The efficacy of the EGCG- liposomal paclitaxel combination in patients with breast cancer or other solid tumors warrants further study. So we recommend applying PTX loaded liposomes with EGCG in vivo to determine their effectiveness systemically.
- Liposomal formulations for EGCG must be synthesized and their antiproliferative and proapoptotic effect in MCF7 breast cancer cells should be studied.
- Liposomal paclitaxel can be functionalized to be targeted to specific tumor site in vivo.