Preparation And Basic Properties Of The Amphiphilic Chitosan Derivatives

Chitosan, a polymer of glucosamine, is a deacetylated product of chitin, which is a byproduct of crab and shrimp processing. As a natual cational polymer of glucosamine, chitosan have several advantages, such as availability from replenishable agricultural or marine food resources, biocompatibility, biodegradability, therefore leading to ecological safety and the possibility of preparing a variety of chemically or enzymatically, modified derivatives for specific end uses. But chitosan just can dissolve in some dilute organic and inorganic acid, which limit the area of application enormously. In our study, chitosan was hydrophilically modified by O-carboxymethylation to increase the flexibility of chitosan molecular chains in water, then followed by the hydrophobic modification with alkyl to yield novel polymeric amphiphiles, alkyl-modified O-carboxymethylation chitosan conjugates, which make it have the amphiphilic property and can self-assemble to enlarge the extent of application.1. Physicochemical characteristics of self-aggregates of chitosan derivatives and basic applicationA series of chitosan derivatives with butyl, hexyl, and octyl groups as hydrophobic moieties and O-carboxymethyl group as hydrophilic moiety, respectively, were successfully synthesized. These N-alkyl-O-carboxymethylation amphiphilic chitosan derivatives were first characterized with 1H NMR, 13C NMR, FT-IR and elemental analysis (EA). And their physical properties were measured by thermogravimetric (TG) and differential scanning calorimetry (DSC). The critical micelle concentrations (cmc) of the modified chitosans determined by using pyrene as a hydrophobic probe in fluorescence spectroscopy were found to be 0.6 mg/mL ~ 4.19 mg/mL. These chitosan derivatives were also evaluated for their micelle-forming properties using dynamic light scanning (DLS) and transmission electron microscopy (TEM) techniques. Their morphologies were changed with varying the length of alkyl group. These data suggested that novel N-alkyl-O-carboxymethylation chitosan derivatives could self-assemble to form sphere polymeric micelles with 202 to 538 nm diameter.In addtion,we describe a novel drug delivery system for the well known demulcent drug, ibuprofen (Ibu). This system is the aggregates of N-alkyl-O-carboxymethylation chitosan (Cn-OCMCS, n = 4, 6, 8), which is a kind of biocompatible and amphiphilic chitosan derivative. The amount of drug loaded was examined by stead-state fluorescence. The release behaviors of Ibu from this proposed controlled release system in PBS solution at 37°C were studied by UV-vis spectroscopy. The results demonstrate that the aggregates of Cn-OCMCS (n = 4, 6, 8) can help to enhance the solubility of Ibu. After Ibu is loaded in Cn-OCMCS (n = 4, 6, 8), the release of Ibu is significantly sustained, which is caused by the interactions between Cn-OCMCS (n = 4, 6, 8) and lipophilic Ibu. These findings propose a new concept of a localized drug delivery.2. The interaction of Cn-OCMCS (n = 4,6,8) and BSAThe influence of amphiphilic chitosan derivatives on the conformation of bovine serum albumin (BSA) micelles was investigated using fluorescence spectra, isothermal titration calorimetry (ITC), circular dichroism (CD), dynamic light scattering (DLS) and transmission electron microscopy (TEM) techniques. The results show that the chain of the Cn-OCMCS (n = 4, 6, 8) combine with the hydrophobic part of BSA through hydrophobic function to make the structure of BSA looser in the system of Cn-OCMCS (n = 4, 6, 8) and BSA. In a certain extent, the peptide has been de-spiral and the conformation of bovine serum albumin (BSA) have been changed. Cn-OCMCS (n = 4, 6, 8) mainly reacts with tryptophan residue of BSA and the exposure of tryptophan residue to make the intensity of the fluorescence enlarged. Moreover, with increasing the long of hydrophobic chain, association function increases.3. Vesicle formation and stability in mixed systems of amphiphilic chitosan derivatives and cationic conventional surfactantThe self-assembly behavior of mixed solutions consisting of amphiphilic chitosan derivatives Cn-OCMCS (n = 4, 6, 8) and cationic conventional surfactant hexadecyl trimethyl ammonium bromide (CTAB) is investigated. A number of techniques like transmission electron microscopy (TEM), dynamic light scattering (DLS), isothermal titration calorimetry (ITC), small-angle X-ray diffraction (SAXD), Uv-vis and zeta potential measurement have been utilized for characterization of the self-assemblies in aqueous solution. Spherical vesicles of the 180 ~ 250 nm diameters are formed spontaneously in the polymer-rich systems of the Cn-OCMCS (n = 4, 6, 8) / CTAB mixture, and a long enough hydrophobic chain length of the Cn-OCMCS (n = 4, 6, 8) which can enhance the aggregation ability of the mixed system, is beneficial to form vesicle in this kind of mixed system. Combined with the above results, the driving forces of vesicle-formation in this kind of system are attributed to the strong electrostatic interaction and the hydrophobic interaction. Moreover, these vesicles show different stabilities to aging time, salt and temperature.