الفهرس 
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Abstract
Cancer is a group of diseases characterized by the spread of abnormal cells and their uncontrolled growth.
If the spread is not controlled, it can result in death. One of the most common cancers is breast cancer and it has a high incidence rate in all countries.
The main lines of treatment for breast cancer are radiation therapy (RT), chemotherapy (CT), surgery and targeted therapy. Negative impact on health-relatedquality of life is the result of the several chemotherapy adverse effects such as hair loss, depressed immunity, fatigue, gastrointestinal disturbances and neutropenia.
Nanoparticles (NPs) show interesting characteristics as small sizes, large surface-to-volume ratios, high drug loading capacity, self-assembly capacity, and biocompatibility.
Consequently, they have the potential to increase both selectivity and potency of chemical, physical, and biological approaches for eliciting cancer cell death while lowering the toxicity to nonmalignant cells.
Natural polymers have exceptional properties including biodegradability, non-antigenicity, compatibility, high nutritional value, abundant renewable sources, good tailoring ability and extraordinary binding capacity of various drugs for a wide range of clinical application.
Lactoferrin (LF) is an iron-binding glycoprotein of transferrin family of iron transporter proteins that regulates the concentration of iron ions in blood and secretory fluids, exerts antimicrobial and antiviral action.
In addition, LFis easy to purify and soluble in water allowing ease of delivery by injection and shows an ideal candidate for NPs preparation.
Alginateis an anionic polysaccharide present in the cell walls of algae.
Alginates have been exploited as pharmaceutical biopolymerin the development of various kinds of drug delivery systems like tablets , capsules, buccal patches , beads , microparticles, and nanoparticles, etc. Sodium alginate is a neutral salt in which the carboxyl groups of alginatesare bonded with a sodium ion.
Sodium alginate is soluble in both cold and hot water to produce a smooth viscous solution.In this study, we propose for the first time up to our knowledge, ALG-LF nanohybrids for co-delivery of PMT, RST and HK to breast cancer, scheme4.
First the drug, RST, was covalently-XXVII bonded to the LF polymer via amide bond stable at systemic circulation but can be cleaved at tumor cells thus enabling its sustained and specific release at tumor sites.
Second the highly hydrophilic drug, PMT, was covalently-bonded to the ALG polymer via ester bond stable at systemic circulation but can be cleaved at tumor cells thus enabling its sustained and specific release at tumor sites and reducing its systemic toxicity.
Third, ALG-LF co-polymer was synthesized by carbodiimide coupling of ALG-PMTconjugateand LF-RST conjugate.
Fourth, to overcome its high lipophilicity and enable its parenteral administration, HK was physically incorporated into the hydrophobic core of nanohybrids providing sustained drug release pattern.
Finally, Crosslinking of ALG-LF nanohybrids with genipin to improve their structural stability, preventing their premature disintegration and rapid drug re