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Effects of Molecular Weight and Loading on Matrix Metalloproteinase-2 Mediated Release from Poly(Ethylene Glycol) Diacrylate Hydrogels

The AAPS Journal volume 14, pages 482–490 (2012)Cite this article

Abstract

Herein, we report on continued efforts to understand an implantable poly(ethylene glycol) diacrylate (PEGDA) hydrogel drug delivery system that responds to extracellular enzymes, in particular matrix metalloproteinase-2 (MMP-2) to provide controlled drug delivery. By attaching peptide as pendant groups on the hydrogel backbone, drug release occurs at an accelerated rate in the presence of active protease. We investigated MMP-2 entry and optimized parameters of the drug delivery system. Mesh size for different PEGDA molecular weight macromers was measured with PEGDA 3,400 hydrogels having a mesh size smaller than the dimensions of MMP-2 and PEGDA 10,000 and PEGDA 20,000 hydrogels having mesh sizes larger than MMP-2. Purified MMP-2 increased release of peptide fragment compared to buffer at several loading concentrations. Cell-stimulated release was demonstrated using U-87 MG cells embedded in collagen. GM6001, an MMP inhibitor, diminished release and altered the identity of the released peptide fragment. The increase in ratio of release from PEGDA 10,000 and PEGDA 20,000 hydrogels compared to PEGDA 3,400 hydrogels suggests MMP-2 enters the hydrogel. PEGDA molecular weight of 10,000 and 15 % (w/V) were the optimal conditions for release and handling. The use of protease-triggered drug delivery has great advantage particularly with the control of protease penetration as a parameter for controlling rate of release.

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ACKNOWLEDGMENT

The authors would like to thank Dr. William Beck for use of equipment. We thank Dr. J.H. “Robert” Chang for insightful discussion. This work was supported by NIH R01 NS055095 (RAG). This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR15482 from the National Center for Research Resources, NIH.

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Affiliations

  1. Department of Bioengineering, University of Illinois, Chicago, Illinois, 60607-7052, USA

    Amy E. Ross & Richard A. Gemeinhart

  2. Department of Biopharmaceutical Sciences, University of Illinois, Chicago, Illinois, 60612-7231, USA

    Mary Y. Tang & Richard A. Gemeinhart

  3. Department of Ophthalmology and Visual Science, University of Illinois, Chicago, Illinois, 60612-4319, USA

    Richard A. Gemeinhart

  4. 833 South Wood Street (MC 865), Chicago, Illinois, 60612, USA

    Richard A. Gemeinhart

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  1. Amy E. Ross
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Correspondence to Richard A. Gemeinhart.

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Ross, A.E., Tang, M.Y. & Gemeinhart, R.A. Effects of Molecular Weight and Loading on Matrix Metalloproteinase-2 Mediated Release from Poly(Ethylene Glycol) Diacrylate Hydrogels. AAPS J 14, 482–490 (2012). https://doi.org/10.1208/s12248-012-9356-3

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KEY WORDS

  • cancer
  • chemotherapy
  • controlled drug delivery
  • enzyme-triggered drug delivery
  • matrix metalloproteinase-2
  • poly(ethylene glycol) diacrylate, hydrogel