Jong-Ho Kima, d, 1, Yoo-Shin Kimb, c, 1, Sungwon Kima, d, Jae Hyung Parke, Kwangmeyung Kima, d, Kuiwon Choia, Hesson Chunga, Seo Young Jeongf, Rang-Woon Parkb, c, In-San Kimb, c, Ick Chan Kwona, d
a Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea
b Department of Biochemistry, School of Medicine, Kyungpook National University, Dong-In 2-101, Jung-gu, Daegu 700-422, South Korea
c Advanced Medical Technology Cluster for Diagnosis and Prediction, 101 Dong-In 2-101, Jung-gu, Daegu 700-422, South Korea
d KIST Regional Laboratory in Advanced Medical Technology Cluster for Diaganosis and Prediction, 101 Dong-In 2-101, Jung-gu, Daegu 700-422, South Korea
e Department of Advanced Polymer and Fiber Materials, College of Environment and Applied Chemistry, KyungHee University, Gyeonggi-do 449-701, South Korea
f Department of Pharmaceutics, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemoon-gu, Seoul 130-701, South Korea
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 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.
Keywords : Hydrophobically modified glycol chitosan; Paclitaxel; Nanoparticles; In vivo anti-tumor effect