Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation - PubMed (original) (raw)

Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation

K Oka et al. Pharm Res. 1990 Aug.

Abstract

Intestinal absorption of neocarzinostatin (NCS) and smancs (copolystyrene maleic acid-conjugated NCS), in aqueous and oily formulations, was investigated after oral administration in mice. Blood concentrations of NCS and smancs were determined with a cytotoxicity assay employing the highly sensitive Epstein-Barr (EB) virus-transformed B-lymphoblastoid cell line, TK/B. Smancs was more efficiently absorbed from a medium-chain triglyceride solution (oily smancs) than from an aqueous solution in phosphate-buffered saline (PBS). The maximum blood concentration and the area under the concentration curve versus time course (AUC) of oily smancs were 9 and 11 times greater than those of the aqueous form of smancs, respectively. At 5 hr after administration of oily smancs, 0.044% of the total smancs dose was found in blood, whereas the parent compound NCS was not detectable at any time. When oily smancs was administered orally to sarcoma 180 tumor-bearing mice, a selective accumulation of smancs in tumor tissue was observed. These results indicated that a biologically active protein, which cannot be used orally, may be rendered orally active drug by conjugation with a hydrophobic polymer in combination with an oily formulation.

PubMed Disclaimer

Similar articles

• Antitumor activity of orally administered SMANCS, a polymer-conjugated protein drug, in mice bearing various murine tumors.
  Schmitt DA, Kisanuki K, Kimura S, Oka K, Pollard RB, Maeda H, Suzuki F. Schmitt DA, et al. Anticancer Res. 1992 Nov-Dec;12(6B):2219-24. Anticancer Res. 1992. PMID: 1295469
• Immunomodulating activities of orally administered SMANCS, a polymer-conjugated derivative of the proteinaceous antibiotic neocarzinostatin, in an oily formulation.
  Suzuki F, Matsumoto K, Schmitt DA, Pollard RB, Maeda H. Suzuki F, et al. Int J Immunopharmacol. 1993 Feb;15(2):175-83. doi: 10.1016/0192-0561(93)90093-e. Int J Immunopharmacol. 1993. PMID: 7682198
• [SMANCS/lipiodol].
  Maeda H. Maeda H. Gan To Kagaku Ryoho. 1994 May;21(6):907-13. Gan To Kagaku Ryoho. 1994. PMID: 8185354 Review. Japanese.
• Intracavitary administration: pharmacokinetic advantages of macromolecular anticancer agents against peritoneal and pleural carcinomatoses.
  Kimura M, Konno T, Miyamoto Y, Kojima Y, Maeda H. Kimura M, et al. Anticancer Res. 1998 Jul-Aug;18(4A):2547-50. Anticancer Res. 1998. PMID: 9703908
• [Recent advances in research on SMANCS].
  Maeda H. Maeda H. Gan To Kagaku Ryoho. 1998 Feb;25 Suppl 1:1-9. Gan To Kagaku Ryoho. 1998. PMID: 9512680 Review. Japanese.

Cited by

• The link between infection and cancer: tumor vasculature, free radicals, and drug delivery to tumors via the EPR effect.
  Maeda H. Maeda H. Cancer Sci. 2013 Jul;104(7):779-89. doi: 10.1111/cas.12152. Epub 2013 Apr 22. Cancer Sci. 2013. PMID: 23495730 Free PMC article. Review.
• Covalent polymer-drug conjugates.
  Elvira C, Gallardo A, Roman JS, Cifuentes A. Elvira C, et al. Molecules. 2005 Jan 31;10(1):114-25. doi: 10.3390/10010114. Molecules. 2005. PMID: 18007281 Free PMC article. Review.
• Macromolecular therapeutics: advantages and prospects with special emphasis on solid tumour targeting.
  Greish K, Fang J, Inutsuka T, Nagamitsu A, Maeda H. Greish K, et al. Clin Pharmacokinet. 2003;42(13):1089-105. doi: 10.2165/00003088-200342130-00002. Clin Pharmacokinet. 2003. PMID: 14531722 Review.
• Targeted enhancement of the biological activity of the antineoplastic agent, neocarzinostatin. Studies in murine neuroblastoma cells.
  Schor NF. Schor NF. J Clin Invest. 1992 Mar;89(3):774-81. doi: 10.1172/JCI115655. J Clin Invest. 1992. PMID: 1531835 Free PMC article.

References

1. 1. Eur J Cancer Clin Oncol. 1983 Aug;19(8):1053-65 - PubMed
2. 1. Int J Pept Protein Res. 1979 Aug;14(2):81-7 - PubMed
3. 1. Cancer Res. 1986 Dec;46(12 Pt 1):6387-92 - PubMed
4. 1. J Biochem. 1977 Jan;81(1):25-35 - PubMed
5. 1. J Pharmacobiodyn. 1985 Apr;8(4):286-95 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations