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العنوان
Biochemical Studies on Chitosan as Cisplatin Carrier
in Hepatocellular Carcinoma in Rats /
المؤلف
Abdelbaky,Shimaa Saber El-hossieny.
هيئة الاعداد
باحث / Shimaa Saber El-hossieny Abdelbaky
مشرف / Dina M. Seoudi
مشرف / Abdel-Rahman B. Abdel-Ghaffar
مشرف / Khaled G. Mohamed
تاريخ النشر
2019.
عدد الصفحات
321p.;
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الكيمياء الحيوية ، علم الوراثة والبيولوجيا الجزيئية
تاريخ الإجازة
1/1/2019
مكان الإجازة
جامعة عين شمس - كلية العلوم - الكيمياء الحيوية
الفهرس
Only 14 pages are availabe for public view

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from 321

Abstract

Liver cancer is the most frequent and dangerous cancer
worldwide. Some factors are leading to liver cancer like the bad
habitats, HCV, HCB and excessive alcohol intakes. The liver
cells are comprised majority of hepatocytes so, the most
common liver cancer is hepatocellular carcinoma.
There several treatments for hepatocellular carcinoma such
as radiation, surgical removes, chemotherapies,
transplantation.…etc. we concerned our study with
chemotherapies especially cisplatin. However, the
chemotherapies were circulating in the blood and cannot
distinguish between non-tumor and tumor cells where it stops
all the rapid growth cells like hair follicles, cells lining the
stomach …. etc which may be normal or tumor cells. The
severe side effects of all chemotherapies like hair loss, ulcers,
mouth sores, loss of appetite, nausea and vomiting, diarrhea,
increased chance of infections (from low white blood cell
counts), easy bruising or bleeding (from low blood platelet
counts), fatigue (from low red blood cell counts)…. etc.
The most common anticancer therapeutic agent used in the
treating of HCC is cisplatin (CDDP) where it is more effective
and potent chemotherapy used in the treatment of multi types of
tumor, such as cancer of the neck and head, melanoma, nonsmall
cell of the cancer of lung, cervical cancer, liver cancer
and nasopharyngeal carcinoma. The main side effect for
cisplatin is acute kidney injury (AKI). Indeed, limiting clinical
use of cisplatin due to its side effect. Although nephrotoxicity is
a sever side effect with cisplatin therapy, the cisplatin was damaged selectively proximal tubule cells with unclear
mechanism.
To improve the efficacy and decrease the severe side effects
of cisplatin, targeted drug delivery to selectively enter the tumor
cells only, thus decreasing the chemotherapy concentration
within non-tumor cells. So, in the present study we were
entrapped cisplatin in a dual ligand vectors for selective
reaching to the carcinoma part of liver tissues to decrease the
side effect of cisplatin.
So, to improve the efficacy of the therapy, we entrapped the
drug in the hepatic targeted dual ligand drug transport way for
treatmenting of liver malignancy, however the drug entered in a
hepatic targeted vector is reached to the tumor cells only of
liver through the specific sites between the cancer liver cells
receptor and vector ligand, and drug that delivers to non-tumor
liver tissue is decrease.
The chitosan was extracted from the shrimp shells by using
the chemical reagents. Chitosan is a linear polysaccharide
polymer which has been widely used for drug delivery system,
which was used in the forms of micro- and nanoparticles of
chitosan, unique chitosan properties. So, it used in the
formation of mucoadhesive compounds, increase the rate of
dissolution specifically to hydrophobic substances, in the using
of drug delivery, with enhancement of absorption of protein are
the most frequent in the therapeutic applications of this
polymer.
Chitosan is a drug carrier which is a polysaccharide
molecule like cellulose, which composed of 2 types of units which there are repeating from N-acetyl-d-glucosamine and dglucosamine,
connected by (1-4)-β-glycosidic linkage.
The -NH2 and -OH gps of chitosan which binded with
glycyrrhetinic acid (GA) and galactose of lactobionic acid
where the increase of selectivity targeting by entrance of either
glycyrrhetinic acid or galactose subunits through these
receptors. However, the amount and activity of the
asialoglycoprotein receptor due to the presence of inhibitors in
serum, where can decrease the capacity of the binding by 95%
of primary HCC, are decrease through the pathogen conditions,
where asialoglycoprotein receptor for selective transport is not
effective alone.
Glycyrrhetinic acid (GA) and galactose subunit of
lactobionic acid reacted with glycyrrhetinic acid (GA) binding
site and AGPR receptor, respectively. Our study was designed a
novel vector GCGA and by 2 steps 1st one is formation of
glycyrrhetinic acid binded with chitosan (GA-CTS) and 2nd one
is formation of LA-modified GA-CTS (GCGA).
Utilization of cisplatin complexed with alginate to prevent
accumulation of platinum in the kidney so, decrease the
nephrotoxicity with the same antitumor activity of cisplatin.
where sodium alginate is a -ve polysaccharide glycosidically
linked of L-guluronate and D-mannuronate residues and was
extracted from marine algae.
However, sodium alginate and chitosan were used in the
drug delivery. Alginate was widely investigated as a drug
delivery carrier. Due to the biodegradability and low toxicity of chitosan so, the presence of chitosan with alginate will increase
the mechanical strength of alginate microparticles.
The nanoparticles of cisplatin-alginate /GCGA formed by
ionotropic gelation method via interaction between negatively
carboxylic unit of alginate with the positively primary amine of
chitosan (dual ligand modified chitosan GCGA) in the presence
of Calcium chloride and tripolyphosphate as crosslinking
reagents for chitosan and alginate respectively.
In previous study, the results documented the potential
effect of GCGA for delivery the drug to the cancer part of the
liver.
In this study we designed the cisplatin-alginate/GCGA
nanoparticles which loaded with strongest chemotherapy,
cisplatin for treating HCC in rats.