Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel.

Abstract

Self-assembled nanoparticles based on hydrophobically modified glycol chitosan (HGC) were prepared as a carrier for paclitaxel. HGC conjugates were prepared by chemically linking 5beta-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 degrees 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.

• Authors: Jong-Ho Kim, Yoo-Shin Kim, Sungwon Kim, Jae Hyung Park, Kwangmeyung Kim, Kuiwon Choi, Hesson Chung, Seo Young Jeong, Rang-Woon Park, In-San Kim, Ick Chan Kwon
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 111 Issue 1-2 Pg. 228-34 (Mar 10 2006) ISSN: 0168-3659 [Print] Netherlands
• PMID: 16458988 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Drug Carriers
• glycol-chitosan
• cremophor EL
• Chitosan
• Paclitaxel
• Glycerol

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry, pharmacology)
• Body Weight (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chitosan (chemistry)
• Drug Carriers (chemistry)
• Glycerol (analogs & derivatives, chemistry)
• Humans
• Hydrophobic and Hydrophilic Interactions
• Injections, Intravenous
• Male
• Melanoma, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred C57BL
• Nanostructures (chemistry)
• Paclitaxel (administration & dosage, chemistry, pharmacology)
• Technology, Pharmaceutical (methods)
• Time Factors
• Treatment Outcome