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العنوان
Self-assembled Amphiphilic Nano-Micelles for Tumor Targted Delivery of selected Anti-Cancer Drugs /
المؤلف
Ibrahim, Doaa Mohamed Anwar.
هيئة الاعداد
باحث / دعاء محمد انور ابراهيم
مشرف / د.ماجدة عبد السميع محمد المسيك
مشرف / جيهان عبد السميع عوض يوسف
مشرف / قدرية عبدالحميد الخضيري
مشرف / د.عدنان أحمد بخيت السيد
الموضوع
Industrial Pharmacy. AntiCancer.
تاريخ النشر
2017.
عدد الصفحات
107 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
العلوم الصيدلية
تاريخ الإجازة
1/1/2017
مكان الإجازة
جامعة الاسكندريه - كلية الصيدلة - الصيدله الصناعيه
الفهرس
Only 14 pages are availabe for public view

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Abstract

Chapter one:
Self-assembled amphiphilic maltodextrin-based micelles for dualtargeted co-delivery of Sulfasalazine and resveratrol to hepatocellular carcinomaIn this study, we propose for the first time up to our knowledge, dual-targeted amphiphilic MD-UDCA micelles for targeted co-delivery of SSZ and RSV for HCC therapy.
First, amphiphilic co-polymer was synthesized by carbodiimide coupling of maltodextrin and DOCA.
Second, the hydrophobic drug, SSZ, was covalently-bonded to the MD fragment of the micelles via amide bond stable at systemiccirculation but can be cleaved at tumor cells thus enabling its specific release at tumor sites and reducing its systemic toxicity.
Third, to overcome its high lipophilicity and enable its parenteral administration, RSV was physically incorporated into the hydrophobic core of micelles providing sustained drug release pattern.
Finally, as an active targeting approach to maximize drug accumulation in tumor cells, the surface of micelles was dual-decorated with FA and LA to facilitate binding to FR and ASGPR thus enhancing internalization into HCC cells via receptor-mediated endocytosis.
Complete physicochemical characterization of the prepared micelleswas performed via determination of the drug content, particle size, polydispersity index, zeta potential, entrapmentefficiency, TEM, DSC and FTIR.
DSC of the prepared micellesshowed the disappearance of the characteristic endothermal peaks of the drugs indicating the conversion of the encapsulated drug (RSV) in the core of the micellesto the amorphous state and effective conjugation of SSZ.
FTIR 96spectra of the prepared formulae showed effective conjugation of SSZ to the surface of the micelles.
Lyophilization of the prepared micelleswas successfully achieved by freeze-drying that maintained their physicochemical characteristics.
Preferable enhanced and sustained release profiles from our fabricated micelleswere successfully achieved.
Our prepared micelles showed good in vitroserum stability without any aggregation observed in serum up to 6 h and accepted hemocompatability.
Chapter two:
Evaluation of the anti-tumor efficacy of the dual targeted drug-loaded maltodextrin micelles in liver cancer cells and animals.For the evaluation of the anti-tumor efficacy of the prepared micelles, the in vitrocytotoxicitystudies of the free drugs and the optimized formulae were examined using MTT reagent.
The in vitrocytotoxicity study on Hep-G2 livercancer cells confirmed the potential of our fabricated micelles to significantly enhance the anti-tumor activity comparedwith free drugs mixtures.
There was an increased level of uptake of dual-targeted micelles compared with untargeted micelles in liver cancer cells, Hep-G2 cells, and the uptake mainly on account of the effective process of FA and ASGPR mediated endocytosis.Biological evaluations of the anti-tumor effects of the probed formulae were done using mice model bearinghepatocellular carcinoma.
The obtained data revealed the superiority of 21 days i.p administration of targeted micellesover the free dual drug solutions.
Mechanistically, the anti-tumor properties of the formulae were correlated to the ability to activate apoptotic enzyme, caspase 3 and marked inhibition VEGF.
These results confirmed the beneficial anti-tumor effects obtained from combining RSV andSSZ in treatment of livercancer.
Histopathological studies were done and different tumor growth biomarkers were determined.
In conclusion, the RSV-loaded (FA-LA-SSZ-MDCA) micelles could be beneficial in treatment of hepatic tumors by targeted delivery of both RSV and SSZ into the tumor cells and further reducing their side effects.