Study Of The Uptake Of Chitosan Oligosaccharide Nanoparticle Delivery

With the implementation of Human Gene Project (HGP) and the further identification of genetical materials cause disease, gene therapy represents a new promising therapeutics modality. The principal problem of gene therapy is focused on transferring genetic material into targeted cells. However, macromolecules such as peptides, proteins, oligonucleotides, and genes are very unstable compounds that need to be protected from degradation in the biological environment. Moreover, their efficacy is highly limited by their ability to across biological barriers and reach the target site. As such, the future of these molecules as therapeutic agents clearly depends on the design of an appropriate carrier for their delivery to the body. The term of efficient and safe gene delivery system should embrace both high efficient and targeted expression of genetic material and effective regulation of expression. Systems currently under study for in vitro and in vivo use include both viral and non-viral vectors. Virus vectors are very effective in terms of transfection efficiency, but they have fatal drawbacks such as immune response and oncogenic effects when used in vivo. Gelsinger's death from a gene therapy clinical trial in 1999 prompteda hard look at the safety record of the viral vectors, and spurred a renewed interest in non-viral methods to ferry genes into tissue. Non-viral vectors are mainly referred to the nanoparticles delivery system such as cationic liposomes, polymers and micelles.Chitosan (CS) is a polysaccharide comprising copolymers of glucosamine and N-acetylglucosamine and can be derived by the partial deacetylation of chitin; a material found in abundance in shells of crustaceans. This cationic polymer has attracted a great deal of attention because of its unique properties, such as acceptable biocompatibility, low toxicity and ability to enhance the absorption of hydrophilic molecules across the Caco-2 cell epithelium via the paracellular transport pathway. Immunohistological studies have shown that chitosan can open the tight junctions between cells through an effect upon F-actin filaments. Recent study on chitosan has attracted interest for converting them to oligosaccharides. Even though chitosan has very strong functional properties in many areas, its high molecular weight, high viscosity and insoluble at physiological pH values (7.2 ~ 7.4) may restrict the uses in vivo. In addition, the action of chitosan in vivo will be influenced because the human gastrointestinal do not possess enzymes directly degrade the p glucosidic linkage in chitosan and consequently the unbroken polymers may be poorly absorbed into the human intestine. Consequently, these data led us to accept that chitosan oligosaccharide (CSO) might be a potential carrier material as drug delivery systems.Nanoparticles formed by ionic gelation of the positively charged polysaccharide chitosan with anionic biomacromolecules has been used in genes, vaccines and anticancer agents administration, and evaluation of the activity of drug-loaded nanoparticles in cell cultures. The traditional role of polymers in colloidal drug delivery systems has been that of an inert excipient. Considering as a new biomacromolecule delivery system, carrier composed of polymers such aschitosan, is requested to uptake intact by the target organism or the target cells, companying with the biomacromolecules. Consequently, the structure and physicochemical properties of this carrier material may affect the uptake process. The investigation about the ability of carrier itself penetrates into the cell is important in evaluation of a potential drug carrier system for drug delivery.Particulate carrier systems have various advantages in the versatility of particulate size and surface characteristics. Hence, it is important to modify particulate characteristics such as size distribution, surface charge, and hydrophilic or hydrophobic property of surface. Among them, self-aggregates of hydrophobically modified polymers have been widely applied in the field of Pharmaceut...