Insulin-containing layer-by-layer films deposited on poly(lactic acid) microbeads for pH-controlled release of insulin

Ryosuke Hashide, Kentaro Yoshida, Yasushi Hasebe, Shigehiro Takahashi, Katsuhiko Sato, Jun Ichi Anzai

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Layer-by-layer (LbL) thin films containing insulin were deposited on the surface of biodegradable poly(lactic acid) (PLA) microbeads and the pH-triggered release of insulin was studied. The LbL films were successfully prepared by the alternate deposition of insulin and poly(vinyl sulfate) (PVS) or dextran sulfate (DS) at pH 4.0 through the electrostatic force of attraction between positively charged insulin and polyanions. The loading of insulin on the microbeads was dependent on the number of insulin layers and the type of polyanions used; higher insulin loading was observed for thicker films and when PVS was used as the polyanion. Insulin was released from the microbeads when they were exposed to neutral solution (pH 7.4) due to a loss of electrostatic attraction between the insulin and polyanions in the films, which in turn was caused by the charge reversal of insulin from positive to negative in the neutral medium. The pH threshold for insulin release was found to be pH 5.0-6.0. The released insulin retained its original secondary structure as evidenced by circular dichroism spectra. The insulin loaded on the microbeads was satisfactorily stable even in the presence of a digestive enzyme (pepsin) at pH 1.5. These results suggest a potential future use for insulin-loaded microbeads in the oral delivery of insulin.

Original languageEnglish
Pages (from-to)242-247
Number of pages6
JournalColloids and Surfaces B: Biointerfaces
Issue number1
Publication statusPublished - 2012 Jan 1


  • Drug delivery system
  • Insulin
  • Layer-by-layer film
  • PH-controlled release
  • PLA microbeads

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry


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