Designing of Chitosan Derivatives Nanoparticles with Antiangiogenic Effect for Cancer Therapy (original) (raw)
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Polymers
The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its mod...
BioResearch Open Access
Many studies have shown that mitochondrial metabolism has a fundamental role in induction of carcinogenesis due to the influence of increased levels of reactive oxygen species (ROS) generation in all steps of oncogene transformation and cancer progression. It is widely accepted that the anticancer effect of conventional anticancer drugs is due to induction of oxidative stress and elevated intracellular levels of ROS, which alter the redox homeostasis of cancer cells. On the other hand, the harmful side effects of conventional anticancer chemotherapeutics are also due to increased production of ROS and disruption of redox homeostasis of normal cells and tissues. Therefore, there is a growing interest toward the development of natural antioxidant compounds from various sources, which could impact the redox state of cancer and normal cells by different pathways and could prevent damage from oxidant-mediated reactions. It is known that chitosan exhibits versatile biological properties, including biodegradability, biocompatibility, and a less toxic nature. Because of its antioxidant, antibacterial, anticancer, anti-inflammatory, and immunostimulatory activities, the biopolymer has been used in a wide variety of pharmaceutical, biomedical, food industry, health, and agricultural applications and has been classified as a new physiologically bioactive material.
Nanomaterials
Chitosan is a fibrous compound derived from chitin, which is the second most abundant natural polysaccharide and is produced by crustaceans, including crabs, shrimps, and lobsters. Chitosan has all of the important medicinal properties, including biocompatibility, biodegradability, and hydrophilicity, and it is relatively nontoxic and cationic in nature. Chitosan nanoparticles are particularly useful due to their small size, providing a large surface-to-volume ratio, and physicochemical properties that may differ from that of their bulk counterparts; thus, chitosan nanoparticles (CNPs) are widely used in biomedical applications and, particularly, as contrast agents for medical imaging and as vehicles for drug and gene delivery into tumors. Because CNPs are formed from a natural biopolymer, they can readily be functionalized with drugs, RNA, DNA, and other molecules to target a desired result in vivo. Furthermore, chitosan is approved by the United States Food and Drug Administration...
2013
Chitosan has increasingly gained popularity in biomedical applications. Experimental results demonstrated that chitosan exhibited anti-microbial activities through its interaction(s) with microbial cell surface. We hypothesized that the properties of chitosan can be exploited to inhibit cancer cell growth. In this study, we investigated the effects of chitosan, chitosan in combination with nanoparticles (nanogold and nanosilver particles), and chitosan in combinations with nanoparticles and/or three therapeutic drugs (Adriamycin, Methotrexate, and Cisplatin) on human brain glioblastoma U87 cells, human pancreatic cancer PANC-1 cells; the results were compared with results of similar treatment on normal human fibroblast BJ cells. We found that chitosan, chitosan in combination with nanoparticles, and the three therapeutic drugs had different inhibition effects on the growth of these three cell types as indicated by MTT assay. The inhibition effects of drugs were greater when combined...
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The study describes the current state of knowledge on nanotechnology and its utilization in medicine. The focus in this manuscript was on the properties, usage safety, and potentially valuable applications of chitosan-based nanomaterials. Chitosan nanoparticles have high importance in nanomedicine, biomedical engineering, discovery and development of new drugs. The manuscript reviewed the new studies regarding the use of chitosan-based nanoparticles for creating new release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity of drugs. Nowadays, effective cancer treatment is a global problem, and recent advances in nanomedicine are of great importance. Special attention was put on the application of chitosan nanoparticles in developing new system for anticancer drug delivery. Pre-clinical and clinical studies support the use of chitosan-based nanoparticles in nanomedicine. This manuscript overviews the last progresses reg...
Artificial Cells, Nanomedicine, and Biotechnology
In recent years, natural and synthetic polymers have attracted much attention due to their great potentials in medical science. In the present study, we have investigated the effect of chitosan-bulk (Chbulk), chitosan nanoparticles (ChNP), chitosan nanoparticles conjugated with glutaraldehyde (ChNP-GA) with an average size of 300-400 nm on human colorectal carcinoma cells (HCT-116) to examine their cytotoxic and anti-cancer abilities. We have evaluated the effects of Ch-bulk, ChNP, ChNP-GA on cancer cells by morphometric and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays respectively. Our results revealed that the Ch-bulk, ChNP, ChNP-GA decreased cell viability, cell proliferation and caused cell death in a concentration-dependent manner. Both morphometric and quantitative analyses confirmed that (Ch-bulk) and Chitosan nanoparticles (ChNP and ChNP-GA) induced concentration-dependent effects on the cancer cells. Among these three, ChNP-GA produced a more profound effect on the survivability with compared to each-bulk and Ch-NP treated groups. A dose of 2 mg/mL did not produced much effect on the cancer cell death, however, a dose of 4 mg/mL-6 mg/ mL produced significant morphological changes like nuclear condensation and augmentation. Interestingly, a dose of 8 mg/mL produced significant cell death 48 hours post-treatment. In addition, during our morphometric analysis, we found that (Ch-bulk) and Chitosan nanoparticles (ChNP and ChNP-GA) treated cells underwent nuclear disintegration and fragmentation which lead to programmed cell death. Our studies demonstrate that the Ch-bulk, ChNP and ChNP-GA holds a great potential in the treatment of colon cancer.
Cancer Nanotechnology
Myricetin is a flavonoid with anticancer properties. This study aimed to formulate myricetin in the form of solid lipid nanoparticles (SLN), decorated with chitosan (CS) and active-targeted with folic acid (FA). After characterization, the in vitro release, cytotoxicity, antioxidant, and ability of the formulation to induce apoptosis using flow cytometry, fluorescent microscopy, and real-time qPCR were examined. Then in vivo anti-angiogenesis on chick chorioallantoic membrane (CAM) and antitumor activities on mice bearing tumor models were investigated. The present study showed that the size of 310 nm and zeta potential of + 30 mV were acceptable for oral administration. The Michaelis–Menten model fitted the drug release pattern with lag during 144 h of the study. The cytotoxicity assay showed that myricetin-SLN-CS-FA significantly killed cancer cells at the concentrations of 6.25, 12.5, 25, 50 and 100 µg/mL (*p < 0.05, **p < 0.01, and ***p < 0.001). The highest level of ap...
Journal of the Mexican Chemical Society
The presence of reactive primary amines in the backbone structure of chitosan enables the derivatization with different functional groups and thereby improving and expanding its properties, such as solubility and mucoadhesiveness, for biomedical applications. In this work, chitosan was grafted with different sources of amino acids (Histidine, Aspartic acid, Glutamic acid, Glycine-Aspartic acid, and Glycine-Glutamic acid), Chitosan and its grafted amino acid derivatives were obtained in very good yield, and they were characterized by Fourier-Transform Infrared Spectroscopy (FTIR), and the resulted spectra confirmed the right structures of chitosan and its different synthesized derivatives. The chitosan and its amino acid derivatives were converted to nanoparticles in size by subjecting them to the sonication method. The Scanning Electron Microscope (SEM) was used to determine the shape and size of the prepared polymeric nanoparticles and the average nanoparticle size counted by the Image-J program. The micrographs revealed that the nanoparticles with spherical shapes and with different sizes were gained, but in general, they are less than 100nm in diameters. In vitro cytotoxicity of chitosan and chitosan derivatives prepared NPs were determined as MTT assay, against different three types of human breast cancer cell lines which are BT cell lines, MCF-7 cell lines, and SKBR3 cell lines. The cell proliferation of each type of breast cancer cell line has appeared to a highly significant decrease (p<0.001), with all types of tested NPs polymers in comparison with the positive control samples, through different periods of the experiment (24, 48, and 72 hours).
Nanotechnology & Applications
Nanoparticles made from natural and synthetic polymers (biodegradable and nonbiodegradable) witness ongoing an interesting area of research and a techno-economic sector with full expansion in many application domains. Therefore, Chitosan was the target in this work. It is obtained with a 98.3% yield, with a high degree of deacetylation (92.1%) from the local shrimp cortex. Chitosan-poly (PEG, PVA, and PVP) derivatives were synthesized by grafting copolymerization of chitosan with PVA, PVP, and PEG polymers, with yield, reached 77%, 78.3, and 87.5% respectively. FT-IR spectra of the chitosan and its derivatives verified the expected copolymers structures desired to be synthesized. All of the chitosan and its grafted polymers were converted to nanoparticles size by subjecting them to sonication method. The scanning electron microscope (SEM) was used to determine the shape and size of the prepared polymeric nanoparticles, and they developed using the ImageJ program. The micrographs revealed that the nanoparticles with spherical shapes and with different sizes were gained, but in general, they are less than 100nm in diameters. The cytotoxicity of the studied chitosan-g-polymers were examined against differentiated three types of breast cancer cell lines, and the results revealed the highly significant (p<0.001), the effect of these polymers in comparing with the non-treated cell lines, especially with chitosan-grafted-poly (ethylene glycol) nanoparticles (CS-g-PEG), the cell viability reduced to 23.