Protein transport across hydrated hyaluronic acid ester membranes: Evaluation of ribonuclease A as a potentially useful model protein

L. D. Simon, W. N. Charman, S. A. Charman, V. J. Stella

Research output: Contribution to journalReview ArticleResearchpeer-review

6 Citations (Scopus)

Abstract

The study of mechanisms governing release of proteins and peptides from polymeric matrices is often complicated by structural instability commonly associated with exposure of proteins to conditions used during matrix incorporation and subsequent release studies. The purpose of the present work was to investigate ribonuclease A (RNase A) as a potential model protein for probing mechanisms of protein release from matrices composed of partially esterified hyaluronic acid. The aqueous stability of RNase A and structural recovery following exposure to organic solvent were evaluated using a variety of analytical techniques, and the permeability of intact RNase A through partially esterified hyaluronic acid membranes was determined. RNase A showed excellent aqueous stability and permeated hyaluronate membranes with no apparent changes in protein size. Also, while CD studies showed significant structural alteration of RNase A dissolved in an organic solvent, this alteration was largely reversible upon evaporation of the solvent and dissolution of the protein residue in aqueous buffer. The biological activity of RNase A was maintained following diffusion through the polymer matrix and release from protein-loaded membranes. Permeability of RNase A through the partially esterified hyaluronic acid membranes was nonlinearly dependent on the degree of polymer esterification, and diffusion behavior of the protein in the hydrated polymer membranes was consistent with Yasuda's free volume theory.

Original languageEnglish
Pages (from-to)273-285
Number of pages13
JournalJournal of Controlled Release
Volume45
Issue number3
DOIs
Publication statusPublished - 1997

Keywords

  • Hyaluronic acid esters
  • Permeability
  • Polymer membranes
  • Protein stability
  • Ribonuclease A

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