Biodegradable dextran-based microspheres for delivery of anticancer drug mitomycin C

• Published in: Biomaterials 2005-09, Vol.26 (26), p.5375-5385
• Main Authors: Cheung, Richard Y., Ying, Yuming, Rauth, Andrew M., Marcon, Norman, Yu Wu, Xiao
• Format: Article
• Language: English
• Subjects: Absorbable Implants; Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Biodegradable MS; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Survival - drug effects; Coated Materials, Biocompatible; Cytotoxicity; Dextran derivatives; Dextrans - chemistry; Diffusion; Dose-Response Relationship, Drug; Drug Delivery Systems - methods; Drug loading and release; Drug Stability; Kinetics and mechanism; Materials Testing; Mice; Microspheres; Mitomycin - administration & dosage; Mitomycin - chemistry; Particle Size
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2005.01.050

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 °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.