Polymeric Nanocarriers With Mucus-Diffusive and Mucus-Adhesive Properties to Control Pharmacokinetic Behavior of Orally Dosed Cyclosporine A

Hideyuki Sato, Yuuki Kaneko, Kohei Yamada, Kurt D. Ristroph, Hoang D. Lu, Yoshiki Seto, Hak Kim Chan, Robert K. Prud'homme, Satomi Onoue

Research output: Contribution to journalArticle

Abstract

The present study develops cyclosporine A (CsA)-loaded polymeric nanocarriers with mucus-diffusive and mucus-adhesive potential to control pharmacokinetic behavior after oral administration for the treatment of inflammatory bowel diseases (IBD). CsA-loaded nanocarriers consisting of polystyrene-block-polyethylene glycol (PEG-CsA) and polystyrene-block-polyacrylic acid (PAA-CsA) were prepared by a flash nanoprecipitation. Both nanocarriers showed redispersibility from lyophilized powder back to uniform nanocarrier with a mean diameter of approximately 150 nm. The nanocarriers exhibited significantly improved release behavior of CsA under pH 6.8 condition compared. A test of mucodiffusion, using artificial mucus, demonstrated the mucus-diffusive and mucus-adhesive potential of PEG-CsA and PAA-CsA, respectively, dependent on the lack of electrostatic interactions between the surface-coated polymer and mucin. Oral administrations of PEG-CsA and PAA-CsA (10 mg-CsA/kg) in rats resulted in significant improvements of absorption, as evidenced by 50- and 25-fold higher bioavailability than crude CsA, respectively. PAA-CsA exhibited more sustained and slower absorption process of CsA than PEG-CsA because of the different diffusion behavior within the mucus layer. In the rat model of IBD, significant suppression of inflammatory symptoms could be achieved by oral treatment with both CsA nanoparticles. These polymeric nanocarriers are promising dosage options to control pharmacokinetic behavior of orally dosed CsA, contributing to the development of safe and effective treatment for IBD.

Original languageEnglish (US)
Pages (from-to)1079-1085
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume109
Issue number2
DOIs
StatePublished - Feb 2020

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • cyclosporine A
  • inflammatory bowel disease
  • pharmacokinetic control
  • polymeric nanocarrier

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