Enhanced Intestinal Absorption of a Hydrophobic Polymer-Conjugated Protein Drug, Smancs, in an Oily Formulation

Kiichiro Oka, Yoichi Miyamoto, Yasuhiro Matsumura, Shohei Tanaka, Tatsuya Oda, Fujio Suzuki, Hiroshi Maeda

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)852-855
Number of pages4
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Volume7
Issue number8
DOIs
StatePublished - Aug 1990
Externally publishedYes

Keywords

  • intestinal absorption
  • oily formulation
  • oral administration
  • polymer drugs
  • protein conjugation
  • smancs

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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