Protein delivery from materials formed by self-selective conjugate addition reactions

Donald L. Elbert, Alison B. Pratt, Matthias P. Lutolf, Sven Halstenberg, Jeffrey A. Hubbell

Research output: Contribution to journalArticlepeer-review

290 Scopus citations


A new chemical cross-linking scheme was utilized for the formation of degradable poly(ethylene glycol) hydrogels suitable for the delivery of protein drugs. An aqueous solution containing a PEG-multiacrylate and solid particles of albumin was mixed with an aqueous solution containing a PEG-dithiol, rapidly producing a cross-linked hydrogel through a Michael-type addition reaction. For some formulations, it was observed that about 65% of the incorporated protein was released with zero-order kinetics over a period of about 4 days. By changing the functionality of the cross-linker, the release of protein could even be delayed for about 4 days, followed by zero-order release. The mechanism for release appeared to be a combination of slow dissolution of protein in the presence of PEG and hindered diffusion of protein through the gel. The cross-linking of the gels was studied rheometrically, and the hydrolytic degradation of the gels was characterized by measuring the swelling of the gels. Biochemical analysis of the released proteins demonstrated that the polymers reacted with each other, but not with proteins. Utilizing the Flory-Rehner and Peppas-Merrill equations, a framework for modeling the protein release from the gels is described.

Original languageEnglish (US)
Pages (from-to)11-25
Number of pages15
JournalJournal of Controlled Release
Issue number1-2
StatePublished - Sep 11 2001


  • Conjugate addition
  • Hydrogel
  • Michael-type addition
  • Poly(ethylene glycol)
  • Protein delivery

ASJC Scopus subject areas

  • Pharmaceutical Science


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