الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
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Abstract
Cancer is one of the world’s major causes of morbidity and mortality. Ehrlich ascites carcinoma (EAC) is one of the most prevalent Experimental cancers with important modeling implications. Chemotherapeutic medicines are frequently employed to eliminate tumor cells, but they all have side effects because they harm healthy cells.
Doxorubicin (DOX) is an anthracycline antibiotic used to treat a variety of cancers for decades. The majority of organs, particularly the heart and liver are poisonous to DOX. DOX causes toxicity by producing free radicals and reactive oxygen species, which increment oxidative stress and depletes the antioxidant system, triggering apoptosis and causing DNA damage.
Nanoparticles have opened up new possibilities for chemotherapy. Targeted drug delivery to the tumor location or a specific group of cells using ingeniously made nanoparticles almost eliminates side effects in normal tissues and organs. Chemical stability, selectivity, sustained drug release, enhanced drug solubility, and lower toxicity are all properties of the suitable nano-carriers that have been studied extensively for targeted drug delivery systems.
Natural polymers have been utilized for nano-capsulation as carriers of drugs because they have key functional groups that can be conjugated to the drugs. Furthermore, polymers can aggregate to produce cross links that can hold and encapsulate the drug with hydrophilic surface.
Pectin is an anionic polysaccharide polymer present in the cell wall of fruits and plants. Pectin-based nanomaterials are suitable for encapsulation due to their properties like Good water solubility, high surface area, biodegradability, cytocompatibility, extended drug half-life and controlled drug release. When compared to bulk pectin, pectin nanoparticles have specific surface area.
The present work was designed to evaluate the antitumor activity and safety of ENC-DOX compared to the commercially used drug DOX in Ehrlich Solid Carcinoma bearing mice.
A total number of 305 adult female Swiss albino mice, weighing 25-30 gm.
1. Anti-tumor Studies
The anti-tumor activities of DOX and/or ENC-DOX were assessed on 215 mice bearing solid Ehrlich Carcinoma that were classified into two main groups, the first group (group A) 40 mice which were used to determine the mortality rate and The second group (group B) 175 mice were used to calculate the mean tumor weight.
A. Mortality rate
40 mice which were used to determine the mortality rate and subdivided into five groups (n=8) as flow:
group 1 EAC Female mice inoculated with EAC cells (2.5 × 106 viable EAC) intramuscularly in the left thigh of each mouse.
group 2 EAC+DOX Female mice bearing EAC, treated with DOX (12mg/kg, i.p.) three days a week for three weeks
group 3 EAC+PNPs Female mice bearing EAC, treated with orally with PNPs (12mg/kg) three days a week for three weeks
group 4 EAC+ DOX+PNPs female mice bearing EAC cells treated with DOX and Pnps as the same previous corresponding dose, period, and route of administration
group 5 EAC+ ENC-DOX Female mice bearing EAC, orally treated with encapsulated doxorubicin (EAC+ENC-DOX) (12mg/kg) three days a week for three weeks
B. The mean tumor weight
The second group 175 mice were used to calculate the mean tumor weight (MTW) until the end of the study and were classified into five equal-sized groups (n=35) as flow: Gr1: EAC group, Gr2: EAC+DOX group, Gr3: EAC+PNPs, Gr4: EAC+DOX+PNPs, Gr5: EAC+ENC-DOX (the animals in these groups were injected as mentioned before).
2. Biochemical and histopathological studies
90 animals were assigned into six groups, each containing 15 mice the animals in these groups from Gr1-Gr5 were injected as mentioned before. Gr 6 served as control group.
At the end of the experiment period, all groups of mice under study were dissected. Blood samples were drawn and serum was separated from them. Liver and heart organs were separated for histological analyzes. Samples were taken from the liver and heart for biochemical analyzes, which included some antioxidants, namely SOD, glutathione GSH and glutathione reduced GPX, in addition to measuring indicators of oxidative stress, including the rate of MDA lipid peroxidation. Inflammation indices such as tumor necrosis factor α-TNF and MCP-1 were also measured. Liver and heart samples were taken to measure the indices of apoptosis, caspase-3 and p53, and the measurement of anti-apoptotic protein Bcl2, in addition to measuring CRP and liver alpha gene protein AFP. The serum was also used to measure liver enzymes, including ALT aminotransferase and AST. Serum creatine CK and LDH lactate were also measured.
The results of the present study were as follows:
The results revealed that there were no changes between the doxorubicin coated group and the control group.
• Treatment of EAC mice with ENC-DOX resulted in a reduction in mean tumor weight (MTW) and an improvement in MST as well as an increase in life span (ILS) compared to the treatment with free DOX.
• Administration of DOX to EAC mice led to a significant increase in MDA in liver and heart tissues, accompanied by a decrease in the antioxidant factors SOD, GSH and GPX. In contrast, treatment with ENC-DOX caused a clear improvement in both oxidative and anti-oxidant factors.
• Regular administration of DOX also caused a significant increase in inflammatory markers TNF-α and MCP in liver and heart tissues, and treatment with ENC-DOX resulted in an improvement in inflammatory markers.
• Apoptotic markers caspase-3 and p53 were decreased after treatment with ENC-DOX and the anti-apoptotic protein Bcl2 was also increased.
• DOX administration elevated the levels of AFP and CRP in liver tissues. Also, ALT and the AST in the liver tissues were increased, in addition to the increase in the levels of CK and LDH in the heart. While these levels improved after treating with ENC-DOX
• Less histological lesions were observed in the liver and heart tissue sections of the ENC-DOX treated mice compared to the higher histological lesions observed in the liver and heart in the EAC group and the normal DOX treated group.
Based on the previous results, this study concludes that loading and encapsulating doxorubicin on nano-pectin improves the efficiency of doxorubicin in fighting tumors via reducing tumor weight and increasing the life span, in addition to reducing toxicity to vital organs due the o active role of ENC-DOX as an anti-oxidant, anti-apoptotic and anti-inflammatory.
In light of the foregoing, we can emphasize the preference of using modern nanometric methods based on natural extracts such as nanopectin as a preventive means against the toxicity caused by doxorubicin in mice.
CONCLUSION AND RECOMMENDATIONS
Despite the abroad spectrum use of DOX as anticancer agent; its clinical applications are limited owing to its-induced hepatotoxicity and cardiotoxicity. Pectin nanoparticles PNPs are widely used in drug delivery systems and develop effective carrier for DOX. Encapsulation of doxorubicin on Pectin nanoparticles improved DOX effect in all examined parameters of liver and heart tissues in mice comparing with DOX and tumor bearing animals. This study proved that the drug encapsulation on the pectin nanoparticles is safer than free DOX.