Biodegradable dextran-based microspheres for delivery of anticancer drug mitomycin C.
The purpose of this work was to develop a biodegradable microsphere (MS) system for delivering mitomycin C (MMC). Various dextran-based MS systems were investigated for their loading and release characteristics, including nonionic MS, sulfopropyl dextran microspheres (SP-MS) with low or high cross-linking density, oxidized SP-MS (Ox-MS), and hydrophobically modified SP-MS. SP-MS were chemically modified by oxidation with sodium periodate or by reaction with anhydride. The chemical structure of modified SP-MS and MMC-loaded MS (MMC-MS) were examined using Fourier transform infrared (FTIR) and solid-state nuclear magnetic resonance (NMR) spectrophotometry. Drug release was conducted at 37 degrees C in aqueous solutions of 0.15 m phosphate buffer solution. The kinetics of drug absorption and release and the stability of MMC after loading and release were determined by spectrophotometry and high-performance liquid chromatography. Ionic SP-MS exhibited a higher drug-loading rate and capacity when compared to nonionic MS, while hydrophobically modified SP-MS showed an even greater loading capacity than SP-MS. These results suggest that both ionic complexation and hydrophobic interaction were important factors in MMC loading. The Ox-MS system demonstrated higher drug-loading capacity, more fractional drug release and a longer time to reach release equilibrium as compared to other investigated MS systems. Under optimized reaction and loading conditions, MMC released from Ox-MS was found to be unaltered. This work demonstrates that the Ox-MS system is a potentially useful system for the delivery of MMC.
Cheung
Richard Y
RY
Faculty of Pharmacy, University of Toronto, Ont., Canada M5S 2S2.
Ying
Yuming
Y
Rauth
Andrew M
AM
Marcon
Norman
N
Yu Wu
Xiao
X
D020341:Absorbable Implants; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D003911:Dextrans / Q000737:chemistry*; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D008422:Materials Testing; D051379:Mice; D008863:Microspheres; D016685:Mitomycin / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size
D000903:Antibiotics, Antineoplastic; D020099:Coated Materials, Biocompatible; D003911:Dextrans; D016685:Mitomycin