Preparation Of Alkyl-chitosan Nanoparticles As A Drug Delivery System

Chitosan (CS) is a natural cationic polysaccharide. As a biocompatible and slowly degradable polymer, chitosan has been widely used in drug delivery systems (DDS) especially in drug-controlled release, targeting, and intellectualized delivery system. After modified chemically by alkyl, this kind of alkyl-chitosan consisting of hydrophilic and hydrophobic segments can form nanoparticles with core/shell structure in aqueous media. These nanoparticles have been proposed to use as drug delivery vehicles for poorly water-soluble drugs.Infrared (IR) spectra of alkyl-chitosan revealed that there was a substitution reaction mainly on the amine groups of CS. X-ray photoelectron spectroscopy (XPS) indicated that the higher reaction activity of alkyl halide, the more alkyl substitution degree on hydroxyl group of chitosan. The sizes of alkyl-chitosan aggregates were measured by Dynamic Light Scattering(DLS). The morphology of alkyl-chitosan nanoparticles (ACNPs) was investigated by Transmission Electron Microscope(TEM). The result showed that the ACNPs appeared spheres with a core/shell structure and a scale of 20 to 200nm in size. After carrying drugs, there are obvious changes in the cores of particles with larger diameters.By using paracetamol (PCTM) and paclitaxel (taxol(r)) as model drugs, the vitro release rates of drugs from ACNPs in phosphate buffer solution (PBS, pH=7.4) can be delayed with the increase of degree of substitution alkyl and the increase of carbon chain length of alkyl substituting group. The release of PCTM from ACNPs, however, is much fast than paclitaxel in PBS with a burst effect.Several mathematical models of drug release were used to fit the vitro release of PCTM and taxol from ACNPs. The Weibull model could fit better both PCTM and taxol release profile, and the first order model could fit PCTM release profile better. The dissolution model could fit release profiles of PCTM best than Weibull model and first order model, which was formulated by to assume that the dissolution of PCTM crystals was considered the rate-controlling mechanism of drug release.