Hydrophobically Modified Glycol Chitosan Research Articles

Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel

Self-assembled nanoparticles based on hydrophobically modified glycol chitosan (HGC) were prepared as a carrier for paclitaxel. HGC conjugates were prepared by chemically linking 5β-cholanic acid to glycol chitosan chains using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry. In phosphate-buffered saline (PBS; pH 7.4), the synthesized HGC conjugates formed nano-sized particles with a diameter of 200 nm and exhibited high thermodynamic stability as reflected by their low critical aggregation concentration (0.03 mg/ml). Paclitaxel was efficiently loaded into HGC nanoparticles up to 10 wt.% using a dialysis method. The paclitaxel-loaded HGC (PTX-HGC) nanoparticles were 400 nm in diameter and were stable in PBS for 10 days. These PTX-HGC nanoparticles also showed sustained release of the incorporated of paclitaxel (80% of the loaded dose was released in 8 days at 37 °C in PBS). Owing to sustained release, the PTX-HGC nanoparticles were less cytotoxic to B16F10 melanoma cells than free paclitaxel formulated in Cremophor EL. Injection of PTX-HGC nanoparticles into the tail vein of tumor-bearing mice prevented increases in tumor volume for 8 days. Finally, PTX was less toxic to the tumor-bearing mice when formulated in HGC nanoparticles than when formulated with Cremophor EL.

Self-assembled nanoparticles containing hydrophobically modified glycol chitosan for gene delivery

A self-assembled nanoparticle was prepared using a hydrophobically modified glycol chitosan for gene delivery. A primary amine of glycol chitosan was modified with 5β-cholanic acid to prepare a hydrophobically modified glycol chitosan (HGC). The modified chitosan spontaneously formed DNA nanoparticles by a hydrophobic interaction between HGC and hydrophobized DNA. As the HGC content increased, the encapsulation efficiencies of DNA increased while the size of HGC nanoparticles decreased. Upon increasing HGC contents, HGC nanoparticle became less cytotoxic. The increased HGC contents also facilitated endocytic uptakes of HGC nanoparticles by COS-1 cells, which were confirmed by a confocal microscopy. The HGC nanoparticles showed increasing in vitro transfection efficiencies in the presence serum. In vivo results also showed that the HGC nanoparticles had superior transfection efficiencies to naked DNA and a commercialized transfection agent. The HGC nanoparticles composed of hydrophobized DNA and hydrophobically modified glycol chitosan played a significant role in enhancing transfection efficiencies in vitro as well as in vivo.

Self-assembled nanoparticles based on glycol chitosan bearing 5β-cholanic acid for RGD peptide delivery

The synthetic peptide bearing Arg–Gly–Asp (RGD) sequence is considered to specifically bind to α vβ 3 integrin expressed on endothelial cells in the angiogenic blood vessels, which provides a potential to inhibit the tumor growth. As a carrier for the RGD peptide, hydrophobically modified glycol chitosan (HGC) capable of forming nano-sized self-aggregates was prepared by the chemical conjugation of 5β-cholanic acid to the main backbone of glycol chitosan. The RGD peptide labeled with fluoresein isothiocyanate (FITC-GRGDS) was loaded into self-aggregates in three different conditions: simple mixing, sonication, and solvent evaporation methods. Of different methods applied, solvent evaporation method showed the most promising results for peptide loading, as judged by the yield (>70%) and loading efficiency (>75%). It was found that the presence of FITC-labeled peptides makes the self-aggregates to be compact, possibly due to the role of both hydrophobic FITC and peptides containing carboxylic acids that allow hydrogen bonding and electrostatic interaction with the primary amino groups in the main backbone of glycol chitosan. FITC-labeled peptides were released from self-aggregates in a physiological solution (pH 7.4) for up to 1 day. From the cell adhesion and migration assays, it was demonstrated that FITC labeling of peptides does not significantly deteriorate biological activity of the parent peptide drug (GRGDS). Overall, the self-aggregates loaded with FITC-GRGDS might be useful for monitoring or destroying the angiogenic vessels surrounding the tumor tissue.