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

K. Oka, Y. Miyamoto, Y. Matsumura, S. Tanaka, T. Oda, Fujio Suzuki, H. Maeda

Research output: Contribution to journalArticle

19 Citations (Scopus)

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
Volume7
Issue number8
StatePublished - 1990
Externally publishedYes

Fingerprint

Zinostatin
Conjugated polymers
Intestinal Absorption
Polymers
Blood
Pharmaceutical Preparations
Area Under Curve
Tumors
Proteins
Bearings (structural)
Sarcoma 180
Cytotoxicity
Human Herpesvirus 4
Viruses
Oral Administration
Assays
Neoplasms
Triglycerides
Phosphates
Cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Oka, K., Miyamoto, Y., Matsumura, Y., Tanaka, S., Oda, T., Suzuki, F., & Maeda, H. (1990). Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation. Pharmaceutical Research, 7(8), 852-855.

Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation. / Oka, K.; Miyamoto, Y.; Matsumura, Y.; Tanaka, S.; Oda, T.; Suzuki, Fujio; Maeda, H.

In: Pharmaceutical Research, Vol. 7, No. 8, 1990, p. 852-855.

Research output: Contribution to journalArticle

Oka, K, Miyamoto, Y, Matsumura, Y, Tanaka, S, Oda, T, Suzuki, F & Maeda, H 1990, 'Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation', Pharmaceutical Research, vol. 7, no. 8, pp. 852-855.
Oka, K. ; Miyamoto, Y. ; Matsumura, Y. ; Tanaka, S. ; Oda, T. ; Suzuki, Fujio ; Maeda, H. / Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation. In: Pharmaceutical Research. 1990 ; Vol. 7, No. 8. pp. 852-855.
@article{4233813f18594be8a2781e0580e76caa,
title = "Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation",
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.",
author = "K. Oka and Y. Miyamoto and Y. Matsumura and S. Tanaka and T. Oda and Fujio Suzuki and H. Maeda",
year = "1990",
language = "English (US)",
volume = "7",
pages = "852--855",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "8",

}

TY - JOUR

T1 - Enhanced intestinal absorption of a hydrophobic polymer-conjugated protein drug, smancs, in an oily formulation

AU - Oka, K.

AU - Miyamoto, Y.

AU - Matsumura, Y.

AU - Tanaka, S.

AU - Oda, T.

AU - Suzuki, Fujio

AU - Maeda, H.

PY - 1990

Y1 - 1990

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0025044026&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025044026&partnerID=8YFLogxK

M3 - Article

C2 - 2146602

AN - SCOPUS:0025044026

VL - 7

SP - 852

EP - 855

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 8

ER -