Polylysine-Containing Hydrogel Formulation of Fuzapladib, Inhibitor of Leukocyte-Function Associated Antigen-1 (LFA-1) Activation, for Sustained Release

Author:

Higuchi Koji12ORCID,Yamada Kohei1ORCID,Kihara Tsubasa1,Makino Keisuke1,Sasaki Kenta2,Shindo Takeshi2,Shikama Hiroshi2,Sato Hideyuki1ORCID,Onoue Satomi1ORCID

Affiliation:

1. Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka-shi 422-8526, Shizuoka, Japan

2. Healthcare Business Headquarters, Ishihara Sangyo Kaisha, Ltd., 2-3-1, Nishishibukawa, Kusatsu-shi 525-0025, Shiga, Japan

Abstract

The aim of the present study was to develop an injectable hydrogel (HG) formulation of fuzapladib sodium (FZP), an animal drug for acute pancreatitis (AP), with the use of polyethyleneoxide (PEO) and polylysine (pLys), a cationic polymer. A mixture of pLys and FZP was added to PEO to prepare an HG formulation, and the formulation was optimized by release test and viscosity measurements. Circular dichroism (CD) and infrared absorption (IR) spectral analyses were applied to clarify the intermolecular interactions between FZP and pLys. The pharmacokinetic behavior of FZP was evaluated after a subcutaneous administration of FZP samples (2.0 mg-FZP/kg) to rats. Although the immediate release of FZP was observed for the HG formulation, the addition of pLys at a 20-fold amount of FZP or higher led to the sustained release of FZP. Considering release behavior, the concentration of pLys was optimized as 100-fold that of FZP in the HG formulation. CD and IR spectroscopic analyses of FZP and/or pLys demonstrated an intermolecular interaction between FZP and pLys, as evidenced by the slight spectral transition. After a subcutaneous administration of HG formulation containing pLys to rats, compared with FZP alone, significant differences were observed in the pharmacokinetic behavior with a decrease of Cmax from 2.3 to 0.9 mg/mL and slower elimination kinetics. HG formulation using pLys might be a viable dosage option for FZP for the treatment of AP in animals.

Funder

JSPS KAKENHI

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

Reference23 articles.

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