Deoxycholic acid-grafted PEGylated chitosan micelles for the delivery of mitomycin C.
Mitomycin C (MTC) was incorporated to a micelle system preparing from a polymer named deoxycholic acid chitosan-grafted poly(ethylene glycol) methyl ether (mPEG-CS-DA). mPEG-CS-DA was synthesized and characterized by (1)H nuclear magnetic resonance ((1)H-NMR) and Fourier transform infrared spectroscopy. mPEG-CS-DA formed a core-shell micellar structure with a critical micelle concentration of 6.57 µg/mL. The mPEG-CS-DA micelles were spherical with a hydrodynamic diameter of about 231 nm. After poly(ethylene glycol)ylation of deoxycholic acid chitosan (CS-DA), the encapsulation efficiency and drug loading efficiency increased from 50.62% to 56.42% and from 20.51% to 24.13%, respectively. The mPEG-CS-DA micelles possessed a higher drug release rate than the CS-DA micelles. For pharmacokinetics, the area under the curve (AUC) of the mPEG-CS-DA micelles was 1.5 times higher than that of MTC injection, and these micelles can enhance the bioavailability of MTC. mPEG-CS-DA micelles reduced the distribution of MTC in almost all normal tissues and had the potential to improve the kidney toxicity caused by MTC injection.
Department of Pharmaceutics, School of Pharmacy, Jilin Medical College , Jilin City , PR China.
Xiu-Rong
XR
Zhang
Nian-Qiu
NQ
Shi
Yang
Y
Zhao
He-Yun
HY
Zhu
Jiao
J
Guan
Ying
Y
Jin
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D003840:Deoxycholic Acid / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008823:Micelles; D016685:Mitomycin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D003840:Deoxycholic Acid; D011092:Polyethylene Glycols; D016685:Mitomycin; C028210:monomethoxypolyethylene glycol; D048271:Chitosan
Biodistribution; mitomycin C; pharmacokinetics; polymeric micelles; synthesis