Browse > Article

Preparation of Biodegradable Polymer Microparticles Containing 5-FU Using Supercritical Carbon Dioxide  

Jung, Ju-Hee (Department of Chemical and Biochemical Engineering, The University of Suwon)
Jung, In-Il (Department of Chemical and Biochemical Engineering, The University of Suwon)
Joo, Hyun-Jae (Department of Chemical and Biochemical Engineering, The University of Suwon)
Shin, Jae-Ran (Department of Chemical and Biochemical Engineering, The University of Suwon)
Lim, Gio-Bin (Department of Chemical and Biochemical Engineering, The University of Suwon)
Ryu, Jong-Hoon (Department of Chemical and Biochemical Engineering, The University of Suwon)
Publication Information
KSBB Journal / v.23, no.5, 2008 , pp. 452-459 More about this Journal
Abstract
To obtain maximal efficacy with minimal systemic side-effects, many studies have been carried out to achieve the controlled release of 5-fluorouracil (5-FU). In this study, biodegradable poly(L-lactide) (L-PLA) microparticles containing 5-FU were prepared by a process, called aerosol solvent extraction system (ASES), utilizing supercritical carbon dioxide. The effects of various organic solvents, drug/polymer feeding ratio, polymer molecular weight, and blending with the same polymers with different molecular weights on the formation of 5-FU loaded microparticles were investigated under a predetermined operating condition from our previous study. The drug recovery, entrapment efficiency, and in vitro drug release kinetics were determined by HPLC assays. The drug recovery obtained from the ASES process was found to be very high, whereas the drug entrapment efficiency was considerably low in all the experiments due to the poor affinity between L-PLA and 5-FU. These results indicated that the precipitation rate of L-PLA might be quite different from that of 5-FU so that there was little chance to form 5-FU loaded L-PLA microparticles.
Keywords
5-fluorouracil; poly(L-lactide); supercritical carbon dioxide; microparticle;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Langer, R. (2006), Biomaterials for drug delivery and tissue engineering, MRS Bull. 31(6), 477-485   DOI
2 Bahrami, M. and S. Ranjbarian (2007), Production of micro- and nano-composite particles by supercritical carbon dioxide, J. Supercrit. Fluids 40, 263-283   DOI   ScienceOn
3 Kim, J. H., S. Y. Lee, B. Y. Kim, J. H. Ryu, and G. B. Lim (2003), Preparation of L-PLA microparticles using pure and cosolvent-modified supercritical carbon dioxide, Korean J. Biotechnol. Bioeng. 18, 385-392
4 Longley, D. B. and P. G. Johnston (2007), 5-fluorouracil: Molecular mechanisms of cell death, In Apoptosis, Cell Signaling, and Human Diseases: Molecular Mechanisms, Vol. 1, R. Srivastava, Ed., p263, Humana Press, New Jersey
5 Rich, T. A., R. C. Shepard, and S. T. Mosley (2004), Four decades of continuing innovation with fluorouracil: Current and future approaches to fluorouracil chemoradiation therapy, J. Clin. Oncol. 22, 2214-2232   DOI   ScienceOn
6 Guney, O. and A. Akgerman (2002), Synthesis of controlled-release products in supercritical medium, AIChE J. 48, 856-866   DOI   ScienceOn
7 Hussain, M., G. Beale, M. Hughes, and S. Akhtar (2002), Co-delivery of an antisense oligonucleotide and 5-fluorouracil using sustained release poly (lactide-co-glycolide) microsphere formulations for potential combination therapy in cancer, Int. J. Pharm. 234, 129-138   DOI   ScienceOn
8 Faisant N., J. Akiki, F. Siepmann, J. P. Benoit, and J. Siepmann (2006), Effects of the type of release medium on drug release from PLGA-based microparticles: Experiment and theory, Int. J. Pharm. 314, 189-197   DOI   ScienceOn
9 Ritger, P. L. and N. A. Peppas (1987), A simple equation for description of solute release II. Fickian and anomalous release from swellable devices, J. Contro. Rel. 5, 37-42   DOI   ScienceOn
10 Kompella, U. B. and K. Koushik (2001), Preparation of drug delivery systems using supercritical fluid technology, Crit. Rev. Ther. Drug Carr. Syst. 18, 173-199
11 Dorgan, J. R., J. Janzen, M. P. Clayton, S. B. Hait, and D. M. Knauss (2005), Melt rheology of variable L-content poly (lactic acid), J. Rheol. 49, 607-619   DOI   ScienceOn
12 Feng, S. S. and S. Chien (2003), Chemotherapeutic engineering: Application and further development of chemical engineering principles for chemotherapy of cancer and other diseases, Chem. Eng. Sci. 58, 4087-4114   DOI   ScienceOn
13 Jain, R. A. (2000), The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices, Biomaterials 21, 2475-2490   DOI   ScienceOn
14 Blanco-Prieto, M. J., K. Besseghir, O. Zerbe, D. Andris, P. Orsolini, F. Heimgartner, H. P. Merkle, and B. Gander (2000), In vitro and in vivo evaluation of a somatostatin analogue release from PLGA microspheres, J. Control. Rel. 67, 19-28   DOI   ScienceOn
15 Yeo, S. D. and E. Kiran (2005), Formation of polymer particles with supercritical fluids: A review, J. Supercrit. Fluids 34, 287-308   DOI   ScienceOn
16 Fu, Y. J., S. S. Shyu, F. H. Su, and P. C. Yu (2002), Development of biodegradable co-poly (d,l-lactide/glycolic acid) microspheres for the controlled release of 5-FU by the spray drying method, Colloids Surf. B 25, 269-279   DOI   ScienceOn
17 Martin, A. and M. J. Cocero (2008), Micronization processes with supercritical fluids: fundamentals and mechanisms, Adv. Drug Del. Rev. 60, 339-350   DOI   ScienceOn
18 Kim, K. K. and D. W. Pack (2006), Microspheres for drug delivery, In Biological and Biomedical Nanotechnology, A. P. Lee and L. J. Lee, Eds., p19, Springer, New York
19 Mittal, G., D. K. Sahana, V. Bhardwaj, and M. N. V. R. Kumar (2007), Estradiol loaded PLGA nanoparticles for oral administration: Effect of polymer molecular weight and copolymer composition on release behavior in vitro and in vivo, J. Control. Rel. 119, 77-85   DOI   ScienceOn
20 Park, J. H., M. Ye, and K. Park (2005), Biodegradable polymers for microencapsulation of drugs, Molecules 10, 146-161   DOI   ScienceOn
21 Ghaderi, R. (2000), A supercritical fluids extraction process for the production of drug loaded biodegradable microparticles, Ph. D. Dissertation, Division of Pharmaceutics, Uppsala University, Uppsala, Sweden
22 Anderson, J. M. and M. S. Shive (1997), Biodegradation and biocompatibility of PLA and PLGA microspheres, Adv. Drug Del. Rev. 28, 5-24   DOI   ScienceOn
23 Hsu, L. S. F. and T. C. Marss (1980), Determination of 5-fluorouracil in human plasma by high pressure ion-exchange chromatography, Ann. Clin. Biochem. 17, 272-276   DOI
24 Kim, C. (1999), Release kinetics of coated, donut-shaped tablets for water soluble drugs, Eur. J. Pharm. Sci. 7, 237-242   DOI   ScienceOn