Poly(ethylene glycol) hydrogels formed by thiol-ene photopolymerization for enzyme-responsive protein delivery.
Degradable hydrogels have been extensively used in biomedical applications such as drug delivery, and recent interest has grown in hydrogels that degrade in recognition of a cellular response. This contribution describes a poly(ethylene glycol) (PEG) hydrogel platform with human neutrophil elastase (HNE) sensitive peptide cross-links formed using thiol-ene photopolymerization rendering the gel degradable at sites of inflammation. Further, protein therapeutics can be physically entrapped within the network and selectively released upon exposure to HNE. HNE-responsive hydrogels exhibited surface erosion where the degradation kinetics was influenced by changes in peptide k(cat), concentration of HNE, and concentration of peptide within the gel. Using this platform, we were able to achieve controlled, zero-order release of bovine serum albumin (BSA) in the presence of HNE, and release was arrested in the absence of HNE. To further exploit the advantages of surface eroding delivery systems, a smaller protein (carbonic anhydrase) was delivered at the same rate as BSA and only dependent on gel formulation and environmental conditions. Also, protein release was predicted from a 3-layered hydrogel device using mass loss data. Lastly, the bioactivity of lysozyme was maintained above 90% following the exposure to thiol-ene photopolymerization conditions.
Aimetti
Alex A
AA
Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA.
Machen
Alexandra J
AJ
Anseth
Kristi S
KS
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002417:Cattle; D016503:Drug Delivery Systems; D004798:Enzymes / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D007249:Inflammation; D007700:Kinetics; D019272:Leukocyte Elastase / Q000737:chemistry; D008027:Light; D009113:Muramidase / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013499:Surface Properties
D001672:Biocompatible Materials; D004798:Enzymes; D020100:Hydrogels; D011506:Proteins; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D011092:Polyethylene Glycols; D009113:Muramidase; D019272:Leukocyte Elastase
Biomaterials. 2000 Dec;21(23):2395-404
11055287
FASEB J. 2001 May;15(7):1300-2
11344120
J Control Release. 2001 May 14;72(1-3):101-13
11389989
Eur J Pharm Biopharm. 2000 Jul;50(1):27-46
10840191
J Control Release. 2001 Jun 15;73(2-3):233-44
11516501
Jpn J Physiol. 1999 Feb;49(1):27-33
10219106
Adv Drug Deliv Rev. 2002 Jun 17;54(4):505-30
12052712
J Control Release. 2001 Sep 11;76(1-2):11-25
11532309
J Biomed Mater Res. 1999 Aug;46(2):271-8
10380006
J Control Release. 2004 Jun 18;97(2):333-43
15196760
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5413-8
12686696
Biomaterials. 2001 May;22(9):929-41
11311012
Biomacromolecules. 2009 Jun 8;10(6):1484-9
19408953
Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16242-7
18852471
Biomaterials. 1996 Sep;17(17):1647-57
8866026
Adv Drug Deliv Rev. 1998 May 4;31(3):197-221
10837626
Nat Rev Mol Cell Biol. 2008 Aug;9(8):628-38
18628784
N Engl J Med. 2001 Mar 22;344(12):907-16
11259725
J Biomed Mater Res. 1989 Oct;23(10):1183-93
2808463
Bioconjug Chem. 2001 Mar-Apr;12(2):195-202
11312680
Biomaterials. 2002 Nov;23(22):4315-23
12219821
Biomaterials. 2001 Nov;22(22):3045-51
11575479
Pharm Res. 2006 Mar;23(3):614-22
16397740
Adv Mater. 2009 Dec 28;21(48):5005-5010
25377720
Adv Drug Deliv Rev. 2001 Dec 31;53(3):321-39
11744175
Biomaterials. 2002 Nov;23(22):4307-14
12219820
Adv Drug Deliv Rev. 2006 Nov 30;58(12-13):1379-408
17081649
Biotechnol Bioeng. 2004 Jun 30;86(7):747-55
15162450
Biomacromolecules. 2008 Jan;9(1):75-83
18088094