Controlled delivery of antibacterial proteins from biodegradable matrices

Alma J. Kuijpers, Gerard H.M. Engbers, Pauline B. van Wachem, Jeroen Krijgsveld, Sebastian A.J. Zaat, Jacob Dankert, Jan Feijen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

54 Citations (Scopus)
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Prosthetic valve endocarditis is an infrequent, but serious complication of cardiac valve replacement. The infection is caused by the adherence of bacteria to the prosthetic valve or to tissue at the site of implantation. Recently it was shown that antibacterial peptides from blood platelets are involved in clearance and killing of bacteria adhering to vegetations induced in a model for prosthetic valve endocarditis using rabbits. The application of these antibacterial proteins in a release system, incorporated in the Dacron sewing ring of the prosthetic heart valve would diminish the incidence of endocarditis. In this study a release system for small cationic proteins based on cross-linked gelatin was developed and characterised. Furthermore, the system was evaluated with respect to the uptake and in vitro release of lysozyme, a small cationic protein that was chosen as a model protein for small cationic antibacterial proteins. Variation of gelatin type (A and B), and cross-link density resulted in differences in swelling, thermal behaviour, and number of charged groups. Lysozyme uptake was proportional to swelling, but was governed by the number of anionic groups. The latter was also observed for the release profiles: when the amount of free carboxylic acids is higher (gelatin B compared to gelatin A), the lysozyme release lasts for a longer time period. The release into solidified agarose medium, as a model for heart muscle tissue, was measured. After 50 h, 40–100% of the lysozyme was released, which is in accordance with the aimed release period of 24–48 h. The adsorption experiments in vitro suggest an influence of the electrostatic interactions between lysozyme and gelatin. This hypothesis was validated with a mathematical model which takes both diffusion and adsorption interactions into account.
Original languageEnglish
Pages (from-to)235-247
Number of pages13
JournalJournal of controlled release
Issue number1-3
Publication statusPublished - 1998
Event8th International Symposium on Recent Advances in Drug Delivery Systems 1997 - Salt Lake City, United States
Duration: 24 Feb 199727 Feb 1997
Conference number: 8


  • Gelatin
  • Cross-linking
  • Antibacterial proteins
  • Carbodiimide
  • Endocarditis


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