Abstract
Self-assembling nanospheres of hydrophobized pullulan have been developed. Pullulan acetate (PA), as hydrophobized pullulan, was synthesized by acetylation. Carboxymethylated poly(ethylene-glycol) (CMPEG) was introduced into pullulan acetate (PA) through a coupling reaction using N,N′-dicyclohexyl carbodiimide (DCC). A synthesized PA-PEG-PA (abbreviated as PEP) conjugate was confirmed by Fourier transform-infrared (FT-IR) spectroscopy. Since PEP conjugates have amphiphilic characteristics in aqueous solution, polymeric nanoparticles of PEP conjugates were prepared using a simple dialysis method in water. From the analysis of fluorescence excitation spectra primarily, the critical association concentration (CAC) of this conjugate was found to be 0.0063 g/L. Observations by scanning electron microscopy (SEM) showed the spherical morphologies of the PEP nanoparticles. The particle size distribution of the PEP conjugates was determined using photon correlation spectroscopy (PCS) and the intensity-average particle size was 193.3 ± 13.53 nm with a unimodal distribution. Clonazepam (CNZ), as a model drug, was easy to entrap into polymeric nanoparticles of the PEP conjugates. The drug release behavior was mainly diffusion controlled from the core portion.
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References
Akiyoshi, K., Deguchi, S., Moriguchi, N., Yamaguchi, S., and Sunamoto, J., Self-aggregates of hydrophobized polysaccharides in water. Formation and characteristics of nanoparticles.Macromolecules, 26, 3062–3068 (1993).
Choi, Y., Kim, S. Y., Kim, S. H., Lee, K. S., Kim, C., and Byun, Y., Long-term delivery of all-trans retinoic acid using biodegradable PLLA/PEG-PLLA blended microspheres.Int. J. Pharm., 215, 67–81 (2001).
Davis, S. S.,Emulsion systems for delivery of drugs by the parenteral route. in Optimization of Drug Delivery, Bundgaard, H., Hausen, A. B., Kofod, H. (eds.), Munksgaard, Copenhagen, pp. 198–208 (1984).
Dunn, S. E., Coombes, A. G. A., Garnett, M. C., Davis, S. S., Davies, M. C., and Illum, L.,In vitro cell interaction andin vivo biodistribution of poly(lactide-co-glycolide) nanospheres surface modified by poloxamer and poloxamine copolymers.J. Control Rel., 44, 65–76 (1997).
Dumitriu, S. and Dumitriu, M., Polymeric drug carriers, in Polymeric Biomaterials, S. Dumitriu (ed.), Marcel Dekker, New York, pp. 435–724, (1994).
Estey, E., Thall, P. F., Mehta, K., Rosenblum, M., Brewer T., Simmons, V., Cabanillas, F., Kurzrock, R., and Lopez-Berestein, G., Alterations in tretinoin pharmacokinetics following administration of liposomal all-trans retinoic acid.Blood, 87, 3650–3654 (1996).
Gref, R., Minamitake, Y., Peracchia, M. T., Trubetskoy, V., Torchilin, V., and Langer, R., Biodegradable long-circulating polymeric nanospheres.Science, 263, 1600–1603 (1994).
Hollinger, J. O. (ed.),Biomedical Applications of Synthetic biodegradable Polymers, CRC Press, Boca Raton, (1995).
Jeanes, A., Dextrans and pullulans: industrially significant.ACS Symp. Ser, 45, 284–298 (1997).
Jeong, Y I., Cheon, J. B., Kim, S. H., Nah, J. W., Lee, Y. M., and Sung, Y. K., Akaite, T., and Cho, C. S., Clonazepam release from core-shell type nanoparticlesin vitro.J. Control Rel., 51, 169–178 (1998).
Jung, S. W., Jeong, Y I., and Kim, S. H., Characterization of hydrophobized pullulan with various hydrophobicities.Int. J. Pharm., 254, 109–121 (2003).
Kalyanasundaram, K. and Thomas, J. K., Environmental effects on vibronic band intensities in pyrene monomer fluorescence and their application in studies in micellar systems.J. Am. Chem. Soc., 99, 2039–2044 (1997).
Kaneo, Y., Fujihara, Y., Tanaka, T., Ogawa, K., Fujita, K., and Iguchi, S., Preparation and characterization of a soluble glutathione-dextran conjugate.J. Pharm., 57, 263–272 (1989a).
Kaneo, Y., Fujihara, Y., Tanaka, T., Kozawa, Y., Mori, H., and Iguchi, S., Intrahepatic delivery of glutathione by conjugation to dextran.Pharm. Res., 6(12), 1025–1031 (1989b).
Kreuter, J., Nanoparticle-based drug delivery system.J. Control. Re/., 16, 169–176 (1991).
Kwon, G., Naito, M., Yokoyama, M., Okano, T., Sakurai, Y., and Kataoka, K., Micelles based on AB block copolymers of poly(ethylene oxide) and poly(-benzyl L-asparate).Langmuir, 9, 945–949 (1993).
Kwon, G. S., Naito, M., Yokoyama, M., Okano, T., Sakurai, Y., and Kataoka, K., Physical entrapment of adriamycin in AB block copolymer micelles.Pharm Res., 12, 192–195 (1995).
La, S. B., Okano, T., and Kataoka, K., Preparation and characterization of the micelle-forming polymeric drug indomethacin-incorporated poly(ethylene oxide)-poly(β-benzyl L-aspartate) block copolymer micelles.J. Pharm. Sci., 85, 85–90 (1996).
Langer, R., Polymers in controlled release systems,IBC Paper 1, 1–24 (1989).
Langer, R. and Folkman, J., Polymers for the sustained release of proteins and other macromolecules.Nature, 263, 797–800 (1976).
Lee, J. H., Kopecek, J., and Andrade, J. D., Protein-resistant surfaces prepared by PEO-containing block copolymer surfactants.J. Biomed. Mater. Res., 23, 351–368 (1989).
Lehn, J. M., Supramolecular chemistry.Science, 260, 1762–1763 (1993).
Lewis, D. H., Controlled release of bioactive agents from lactide/ glycolide polymers.Drugs Pharm. Sci., 45, 1–42 (1990).
Majeti N. V. and Ravi Kumar, Nano and microparticles as Controlled Drug Delivery Devices.J. Pharm. Pharmaceut. Sci., 3(2), 234–258 (2000).
Molteni, L., Dextrans as drug carriers, in: Gregoriadis, G. (ed.),Drug Carriers in Biology and Medicine, Academic Press, London, pp. 107–125 (1979).
Motozato, Y., Ihara, H., Tomoda, T., and Hirayama, C., Preparation and gel permeation chromatographic properties of pululan spheres.J. Chromatogr., 355, 434–437 (1986).
Nishikawa, T., Akiyoshi, K., and Sunamoto, J., Supramolecular assembly between nanoparticles of hydrophobized polysaccharide and soluble protein complexation between the self-aggregate of cholesterol-bearing pullulan and α-chymotrypsin.Macromolecules, 27, 7654–7659 (1994).
Poznansky, M. J. and Cleland, L. G., Biological macromolecules as carriers of drugs and enzymes, in: Juliano, R. L. (ed.).Drug Delivery Systems, Oxford University Press, New York, (1980).
Robinson, J. R. and Lee V. H. L., (eds.).Controlled Drug Delivery: Fundamental and Applications, Marcel Dekker, New York, (1987).
Royer, G. P. and Anantharmaiah G. M., Peptide synthesis in water and the use of immobilized carboxypeptidase Y for deprotection,J. Am. Chem. Soc., 101, 3394–3396 (1979).
Schacht, E., Ruys, L., Vermeersch, J., Remon, J. P., Duncan, R., 1985. Use of polysaccharides as drug carriers: dextran and inulin derivatives of procainamide, in: Tirrell, D. A., Donaruma, G., Turek, A. B. (eds.),Macromolecules as Drugs and as Carriers for Biologically Active Materials, The New York Academy of Science, New York, pp. 199–212 (1985).
Stevenson, W. T. K. and Sefton, M. F., Graft copolymer emulsions of sodium alginate with hydroxyalkyl methacrylates for microencapsulation.Biomaterials, 8, 449–457 (1987).
Wilhelm, M., Zaho, C. L., Wang, Y., Xu, R., Winnik, M. A., Mura, J. L., Riess, G., and Croucher, M. D., Poly(styrene-ethylene oxide) block copolymer micelle formation in water: a fluorescence probe study.Macromolecules, 24, 1033–1040 (1991).
Yokoyama, M., Miyauchi, M., Yamada, N., Okano, T., Sakurai, Y., and Kataoka, K., Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycinconjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer.Cancer Res., 50, 1693–1700 (1990).
Yuen, S., Pullulan and its applications.Process Biochem., 9(9), 7–9 (1974).
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Jung, SW., Jeong, Yl., Kim, YH. et al. Self-assembled polymeric nanoparticles of poly(ethylene glycol) grafted pullulan acetate as a novel drug carrier. Arch Pharm Res 27, 562–569 (2004). https://doi.org/10.1007/BF02980132
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DOI: https://doi.org/10.1007/BF02980132