Polyethylene glycol-modified arachidyl chitosan-based nanoparticles for prolonged blood circulation of doxorubicin.
Doxorubicin (DOX)-loaded nanoparticles based on polyethylene glycol-conjugated chitosan oligosaccharide-arachidic acid (CSOAA-PEG) were explored for potential application to leukemia therapy. PEG was conjugated with CSOAA backbone via amide bond formation and the final product was verified by (1)H NMR analysis. Using the synthesized CSOAA-PEG, nanoparticles having characteristics of a 166-nm mean diameter, positive zeta potential, and spherical shape were produced for the delivery of DOX. The mean diameter of CSOAA-PEG nanoparticles in the serum solution (50% fetal bovine serum) remained relatively constant over 72 h as compared with CSOAA nanoparticles (changes of 20.92% and 223.16%, respectively). The sustained release pattern of DOX from CSOAA-PEG nanoparticles was displayed at physiological pH, and the release rate increased under the acidic pH conditions. The cytotoxicity of the CSOAA-PEG conjugate was negligible in human leukemia cells (K562) at the concentrations tested (∼ 100 μg/ml). The uptake rate of DOX from the nanoparticles by K562 cells was higher than that from the solution. Judging from the results of pharmacokinetic studies in rats, in vivo clearance rate of DOX from the CSOAA-PEG nanoparticle group was slower than other groups, subsequently extending the circulation period. The PEGylated CSOAA-based nanoparticles could represent an effective nano-sized delivery system for DOX which has been used for the treatment of blood malignancies.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Ubonvan
U
Termsarasab
College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
In-Soo
IS
Yoon
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Ju-Hwan
JH
Park
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Hyun Tae
HT
Moon
College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: hjcho@kangwon.ac.kr.
Hyun-Jong
HJ
Cho
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: ddkim@snu.ac.kr.
Dae-Duk
DD
Kim
D000818:Animals; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004537:Eicosanoic Acids / Q000737:chemistry*; D006801:Humans; D020014:K562 Cells; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004337:Drug Carriers; D004537:Eicosanoic Acids; D011092:Polyethylene Glycols; D004317:Doxorubicin; D048271:Chitosan; C094477:arachidic acid
Arachidyl chitosan; Doxorubicin; Leukemia; Polyethylene glycol; Prolonged blood circulation