Enhanced Selective Lymphatic Delivery of Cyclosporin A by Solubilizers and Intensified Immunosuppressive Activity Against Mice Skin Allograft

Authors: Takada K.¹; Yoshimura H.²; Yoshikawa H.²; Muranishi S.²; Yasumura T.³; Oka T.³

Source: Pharmaceutical Research, Volume 03, Number 1, February 1986 , pp. 48-51(4)

Publisher: Springer

Abstract:

The absorption and lymphatic delivery of a new immunosuppressive drug, cyclosporin A (CsA), were studied in rats by administering CsA orally after solubilization with HCO-60 (polyoxyethylated hydrogenated castor oil), sugar ester, and oils. After the administration of solubilized CsA (7 mg/kg) to rats with thoracic lymph duct cannulas, both plasma and lymph CsA levels were measured over 6 hr. The lymph CsA levels were strongly affected by the solubilizers. The rank order of the solubilizers in enhancing lymph absorption was HCO-60 (57 µg/ml) > sugar ester (46 µg/ml) > sesame oil (3.5 µg/ml) > linoleic acid (0.4 µg/ml), where the parentheses show the maximum lymph CsA levels. Plasma CsA levels were below 2 µg/ml in each group of animals and were barely altered by the solubilizers. These results support the selective lymphatic delivery of CsA with solubilizers such as HCO-60 and sugar ester. The immunosuppressive activity of CsA (1 mg/kg) solubilized with HCO-60 was nearly equivalent to the sesame oil solution with 7 to 15 mg/kg CsA in the skin-allograft mice model.

Keywords: cyclosporin A; lymphatic delivery; immunosuppressive activity

Language: English

Document Type: Research article

Affiliations: 1: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607, Japan. To whom correspondence should be addressed at Kyoto Pharmaceutical University, Kyoto 607, Japan. 2: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607, Japan. 3: Second Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan.

Publication date: 1986-02-01

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• In this Subject: Pharmacology
• By this author: Takada K. ;  Yoshimura H. ;  Yoshikawa H. ;  Muranishi S. ;  Yasumura T. ;  Oka T.

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