Skip to main content
SpringerLink
Log in

Prolonged Blood Circulation in Rats of Nanospheres Surface-Modified with Semitelechelic Poly[N-(2-Hydroxypropyl)methacrylamide]

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) containing one amino end-group and differing in molecular weight were synthesized by radical polymerization in the presence of 2-aminoethanethiol (AET) as chain transfer agent. These polymers were covalently attached via amide bonds to the surface of nanospheres based on a copolymer of methyl methacrylate, maleic anhydride, and methacrylic acid. When compared to unmodified nanospheres, those with the surface modified with ST-PHPMA possessed a decreased protein (albumin, IgG, fibrinogen) adsorption in vitro, an increased intravascular half-life as well as a decreased accumulation in the liver after intravenous administration into rats. The higher the molecular weight of the ST-PHPMA, the more pronounced the changes in these properties. The results obtained have clearly demonstrated that covalently attached ST-PHPMA chains are efficient in decreasing the biorecognition of negatively charged (hydrophilic) polymer surfaces.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. R. Arshady. Microspheres for biomedical applications: preparation of reactive and labeled microspheres. Biomaterials 14:5–15 (1993).

    Google Scholar 

  2. J. J. Wright and L. Illum. Active targeting of microcapsules and microspheres to specific regions. In M. Donbrow (ed.), Microcapsules and nanoparticles in medicine and pharmacy, CRC Press, Boca Raton, 1992. pp. 281–297.

    Google Scholar 

  3. P. Couvreur, E. Fattal, and A. Andremont. Liposomes and nanoparticles in the treatment of intracellular bacterial infections. Pharm. Res. 8:1079–1086 (1991).

    Google Scholar 

  4. L. Illum, I. M. Hunneyball, and S. S. Davis. The effect of hydrophilic coatings on the uptake of colloidal particles by the liver and peritoneal macrophages. Int. J. Pharm. 29:53–65 (1986).

    Google Scholar 

  5. B. G. Müller and T. Kissel. Camouflage nanospheres: a new approach to bypassing phagocytic blood clearance by surface modified particulate carriers. Pharm. Pharmacol. Lett. 3:67–70 (1993).

    Google Scholar 

  6. J. S. Tan, D. E. Butterfield, C. L. Voycheck, K. D. Caldwell, and J. T. Li. Surface modification of nanoparticles by PEO/PPO block copolymers to minimize interactions with blood components and prolong blood circulation in rats. Biomaterials 14:823–833 (1993).

    Google Scholar 

  7. D. Leu, B. Manthey, J. Kreuter, P. Speiser, and P. P. DeLuca. Distribution and elimination of coated polymethyl [2-14C]-methacrylate nanospheres after intravenous injection in rats. J. Pharm. Sci. 73:1433–1437 (1984).

    Google Scholar 

  8. S. D. Tröster and J. Kreuter. Influence of the surface properties of low contact angle surfactants on the body distribution of 14C-poly(methyl methacrylate) nanoparticles. J. Microencaps. 9:19–28 (1992).

    Google Scholar 

  9. D. Papahadjopoulos, T. Allen, A. Garbizon, E. Mayhew, K. Matthay, S. K. Huang, K.-D. Lee, M. C. Woodle, D. D. Lasic, C. Redemann, F. J. Martin. Sterically stabilized liposomes: improvements in pharmacokinetics, and anti-tumor therapeutic efficacy. Proc. Natl. Acad. Sci. U.S.A. 88:11460–11464 (1991).

    Google Scholar 

  10. F. Fuertges and A. Abuchowski. The clinical efficacy of poly-(ethylene glycol)-modified proteins. J. Controlled Rel. 11:139–148 (1990).

    Google Scholar 

  11. J. H. Lee, P. Kopečková, J. Kopeček, and J. D. Andrade. Surface properties of copolymers of alkyl methacrylates with methoxy (polyethylene oxide) methacrylates and their application as protein-resistant coatings. Biomaterials 11:455–464 (1990).

    Google Scholar 

  12. M. J. Poznansky, M. Shandling, M. A. Salkie, J. Elliott, and E. Lau. Advantages in the use of L-asparaginase-albumin polymer as an antitumor agent. Cancer Res. 42:1020–1025 (1982).

    Google Scholar 

  13. V. Chytrý, J. Kopeček, P. Sikk, R. Sinijärv, and A. Aaviksaar. A convenient model system for the study of the influence of water-soluble polymer carriers on the interaction between protein. Makromol. Chem. Rapid Commun. 3:11–15 (1982).

    Google Scholar 

  14. A. Lääne, A. Aaviksaar, M. Haga, V. Chytrý, and J. Kopeček. Preparation of polymer-modified enzymes of prolonged circulation times. Poly[N-(2-hydroxypropyl)methacrylamide]-bound acetylcholinesterase. Makromol. Chem. Suppl. 9:35–42 (1985).

    Google Scholar 

  15. J. Kopeček and H. Bažilová. Poly[N-(2-hydroxypropyl)-methacrylamide]. I. Radical polymerization and copolymerization. Eur. Polym. J. 9:7–14 (1973).

    Google Scholar 

  16. S. L. Snyder and P. Z. Sobocinski. An improved 2,4,6-trinitrobenzenesulfonic acid method for the determination of amines. Anal. Biochem. 64:284–288 (1975).

    Google Scholar 

  17. M. Okubo, Y. Yamamoto, M. Uno, S. Kamei, and T. Matsumoto. Immunoactivity of polymer microspheres with their hydrophobic/hydrophilic heterogeneous surface sensitized with an antibody. Colloid Polym. Sci. 265:1061–1066 (1987) and references therein.

    Google Scholar 

  18. Č. Koňák, R. C. Rathi, P. Kopečková, and J. Kopeček. Effect of side-chains on solution properties of N-(2-hydroxypropyl)-methacrylamide copolymers in aqueous solvents. Polymer 34:4767–4773 (1993).

    Google Scholar 

  19. H. J. Baker, J. R. Lindsey, and S. H. Weisbroth. Selected normative data. In H. J. Baker, J. R. Lindsey, and S. H. Weisbroth (eds.), The Laboratory Rat, Academic Press, New York, 1979. pp. 412–413.

    Google Scholar 

  20. T. Okano, M. Katayama, I. Shinohara. The influence of hydrophilic and hydrophobic domains on water wettability of 2-hydroxyethyl methacrylate-styrene copolymers. J. Appl. Polym. Sci. 22:369–377 (1978).

    Google Scholar 

  21. Y. G. Takei, T. Aoki, K. Sanui, N. Ogata, T. Okano, and Y. Sakurai. Temperature-responsive bioconjugates. 1. Synthesis of temperature-responsive oligomers with reactive end groups and their coupling to biomolecules. Bioconjugate Chem. 4:42–46 (1993).

    Google Scholar 

  22. L. Illum, L. O. Jacobsen, R. H. Müller, E. Mak, and S. S. Davis. Surface characteristics and the interaction of colloidal particles with mouse peritoneal macrophages. Biomaterials 8:113–117 (1987).

    Google Scholar 

  23. K. P. Antonsen and A. S. Hoffman. Water structure of PEG solutions by differential scanning calorimetry measurements. In J. M. Harris (ed.), Poly(ethylene glycol) chemistry. Biotechnical and biomedical applications, Plenum Press, New York, 1992. pp. 15–28.

    Google Scholar 

  24. M. Bohdanecký, H. Bažilová, and J. Kopeček, Poly[N-(2-hydroxypropyl)methacrylamide]. II. Hydrodynamic properties of dilute solutions. Eur. Polym. J. 10:405–410 (1974).

    Google Scholar 

  25. W. R. Gombotz, W. Guanghui, T. A. Horbett, and A. S. Hoffman. Protein adsorption and elution from polyether surfaces. In J. M. Harris (ed.), Poly(ethylene glycol) chemistry. Biotechnical and biomedical applications, Plenum Press, New York, 1992. pp. 247–261.

    Google Scholar 

  26. G. R. Llanos and M. V. Sefton. Does polyethylene oxide possess a low thrombogenicity? J. Biomater. Sci. Polym. Ed. 4:381–400 (1993).

    Google Scholar 

  27. S. E. Dunn, A. Brindley, S. S. Davis, M. C. Davies, and L. Illum. Polystyrene-poly(ethylene glycol) (PS-PEG2000) particles as model systems for site specific drug delivery. 2. The effect of PEG surface density on the in vitro cell interaction and in vivo biodistribution. Pharm. Res. 11:1016–1022 (1994).

    Google Scholar 

  28. D. Putnam and J. Kopeček. Polymer conjugates with anticancer activity. Adv. Polym. Sci. 122:55–123 (1995).

    Google Scholar 

  29. R. Gref, Y. Minamitake, M. T. Peracchia, V. Trubetskoy, V. Torchilin, and R. Langer. Biodegradable long-circulating polymeric nanospheres. Science 263:1600–1603 (1994).

    Google Scholar 

  30. A. M. Le Ray, M. Vert, J. C. Gautier, and J. P. Benoit. Fate of [14C]poly-(DL-lactide-co-glycolide) nanoparticles after intravenous and oral administration to mice. Int. J. Pharm. 106:201–211 (1994).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah, 84112

    Shigeru Kamei & Jindřich Kopeček

Authors
  1. Shigeru Kamei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jindřich Kopeček
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kamei, S., Kopeček, J. Prolonged Blood Circulation in Rats of Nanospheres Surface-Modified with Semitelechelic Poly[N-(2-Hydroxypropyl)methacrylamide]. Pharm Res 12, 663–668 (1995). https://doi.org/10.1023/A:1016247206531

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1016247206531

Search

Navigation