Journal of Biomedical Engineering Research (대한의용생체공학회:의공학회지)

The Korean Society of Medical and Biological Engineering (대한의용생체공학회)
권호 표지
DOI QR코드

DOI QR Code

Synthesis and Drug-Releasing Behavior of Various Polymeric Prodrugs of PGE1 with PEG and Its Derivative as Polymer Carriers

  • Lee, Chan-Woo (Department of Innovative Industrial Technology, Hoseo University)
  • Published : 2007.08.30
Download PDF
⟨ Previous Next ⟩

Abstract

Two polymeric prodrugs of PGE1 (prodrugs IVg and PNg) were newly synthesized. The drug conjugation proceeded in quantitative yield without decomposition of PGE1 to PGA1. With two types conjugates, PEG-PGE1 and PN-PGE1 with different spacer groups, we first discovered a possibility of slow release of PGE1 in blood circulatory system. PGE1 is conjugated with PEG and PN through the long alkylene spacers, and their availability as polymeric prodrugs is evaluated. Their drug-releasing behavior was examined both in phosphate buffer (pH=7.4) and rat plasma. Each prodrug was known to be highly stabile in the buffer solution. The drug-releasing rate became much faster in rat plasma than in the buffer solution due to the acceleration by the plasma enzymes. The drug-release was found to reach a plateau in rat plasma because the released PGE1 or its derivatives may be captured or decomposed by the plasma proteins. The slower drug-releasing rate of pro drug PNg in rat plasma is reasonably attributed to the molecular aggregation due to the hydrophobic bonding between the PGE1 moieties and spacers.

Keywords

References

  1. C. G. Overberger, Y. Inaki, and Y. Nambu, 'Graft copolymers containing nucleic acid based and L-amino acids,' J. Polymer Sci. Polymer Chem. Ed, vol. 17, pp.1739-1758, 1979 https://doi.org/10.1002/pol.1979.170170616
  2. C. G. Overberger, Y. Inaki, and Y. Nambu, 'Graft copolymers of nucleic acid bases on po1yethy1eneimine: Interaction of the polymers,' J. Polymer Sci. Polymer Chem. Ed, vol. 17, pp. 1759-1769, 1979 https://doi.org/10.1002/pol.1979.170170617
  3. R. Igarashi, Y. Mizushima, M. Takenaga, K. Matsumoto, Y. Morizawa, and A. Yasuda, 'A stable PGE1 prodrug for targeting therapy,' J. Controlled Release, vol. 20, no. 1, pp.37-45, 1992 https://doi.org/10.1016/0168-3659(92)90137-G
  4. K. Inada, T. Wakuda, and K. Uekawa, 'Prostaglandins and their cyclodextrin complexes,' J. Inclusion Phenomena, vol. 2, pp.467-474, 1984 https://doi.org/10.1007/BF00662213
  5. H. Adachi, T. Irie, K. Uekawa, T. Manako, T. Yano and M. Saita 'Combination effects of O-carboxymethyl-O-ethyl-${\beta}$-cyclodextrin and penetration enhancer HPE-101 on transdermal delivery of prostaglandin E1 in hairless mice,' Euro. J Pharma. Sci., vol. 1, no.3, pp.117-123, 1993 https://doi.org/10.1016/0928-0987(93)90001-Q
  6. H. Jacobs, T. Okano, J. T. Lin, and S. W. Kim, 'PGE1 Heparin conjugate releasing polymers,' J. Controlled Release, vol. 2, pp.313-319, 1985 https://doi.org/10.1016/0168-3659(85)90053-7
  7. H. jacobs and S. W. Kim, 'In vitro bioactivity of a synthesized prostaglandin E1-Heparin conjugate,' J. Pharm. Sci., vol. 75, no. 2, pp.172-181, 1986 https://doi.org/10.1002/jps.2600750215
  8. M. Hashida, K. Akamatsu, M. Nishikawa, F. Yamashita, H. Yashikawa, and Y. Takakura, 'Design of polymeric prodrugs of prostaglandin E1 having galactose residue for hepatocyte targeting,' J. Controlled Release, vol. 62, no. 1, pp.253-262, 1999 https://doi.org/10.1016/S0168-3659(99)00045-0
  9. K. D. Altmann, D. Husken, B. Cuenoud, and C. G. Echeverria 'Synthesis and hybridization properties of polyamide based nucleic acid analogues incorporating pyrrolidine-derived nucleoamino acids,' Bioorg. Med. Chem. Lett, vol. 10, pp.929-933, 2000 https://doi.org/10.1016/S0960-894X(00)00121-9
  10. K. Kalyanasundaram and J. K. Thomas, 'Environmental effects on vibronic band intensities in pyrene monomer fluorescence and their application in studies of micellar systems,' J. Am. Chem. Soc. vol. 99, no. 7, pp.2039-2044, 1977 https://doi.org/10.1021/ja00449a004
  11. C. Maltesh, Q. Xu, P. Somasundaran, W. J. Benton, and H. Nguyen, 'Aggregation behavior of and surface tension reduction by comb like amphiphilic polymers,' Langmuir, vol. 8, no. 6, pp.1511-1513, 1992 https://doi.org/10.1021/la00042a004
  12. O. Vorobyova, A. Yekta, and M. A. Winnik, 'Fluorescent probe studies of the association in an aqueous solution of a hydrophobically modified poly(ethylene oxide),' Macromolecules, vol. 31, no. 25, pp.8998-9007, 1998 https://doi.org/10.1021/ma980819l
  13. C. W. Lee, 'Synthesis and properties of multiblock copolymers consisting of oligo(L-lactic acid) and poly(oxyethylene-co-oxypropylene) with different composition,' Korea Polym. J., vol. 9, no. 5, pp.259-266, 2001
  14. C. W. Lee and Y. Kimura, 'In vitro biodegradability and surface properties of block copoly(ester-ether)s consisting of poly (L-Iactide) and polyether,' Macromol. Res., vol. 11, no. 1, pp42-46, 2003 https://doi.org/10.1007/BF03218276
  15. C. W. Lee, 'Synthesis of various polymeric prodrugs of ibuprofen with PEG and its derivative as polymeric carriers,' Macromol. Res., vol. 12, no. 1, pp.63-70, 2004 https://doi.org/10.1007/BF03218996
  16. C. W. Lee, 'Drug-release behavior of polymeric prodrugs of ibuprofen with PEG and its derivatives as polymeric carriers,' Macromol. Res., vol. 12, no. 1, pp.71-77, 2004 https://doi.org/10.1007/BF03218997