In situ forming, resorbable graft copolymer hydrogels providing controlled drug release

Derek J. Overstreet, Richard Huynh, Keith Jarbo, Ryan Y. McLemore, Brent Vernon

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In situ forming hydrogels are promising drug delivery vehicles due to their ease of delivery as liquids and their ability to be used in sites with irregular geometries. In this work, we report on in situ forming, resorbable hydrogels based on N-isopropylacrylamide (NIPAAm) as a fluid-like controlled release gel. These gels are the first resorbable NIPAAm-based gels providing controlled release without relying on affinity between the drug and device. Therefore, these gels provide a more flexible delivery system which can be used to deliver any drug at a controlled rate. The polymers contain repeat units of NIPAAm with (R)-α-Acryloyloxy-β,β-dimethyl-γ-butyrolactone (DBLA) and varying amounts of hydrophilic Jeffamine® M-1000 acrylamide (JAAm) grafts. The graft copolymer architecture allows the water content of the hydrogels to be tuned over a wide range while keeping the initial gelation temperature below body temperature. Incorporation of JAAm in the polymers led to greater water content, faster gel degradation, and reduced burst release. Sustained release of the antimicrobial drugs cefazolin and vancomycin (over about 5 and 7 days, respectively) was observed from gels containing an intermediate amount of grafts which combined reduced phase separation with a degradation time of 40 days. The degradation byproducts of one hydrogel formulation were cytocompatible to NIH 3T3 fibroblasts at concentrations up to 2.5 wt %. This class of terpolymer hydrogels is a promising local delivery system for a wide variety of drugs, particularly for applications involving irregular geometries such as implant interfaces.

Original languageEnglish (US)
Pages (from-to)1437-1446
Number of pages10
JournalJournal of Biomedical Materials Research - Part A
Volume101 A
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Hydrogels
Graft copolymers
Gels
Pharmaceutical Preparations
Acrylamide
Grafts
Degradation
Water content
Polymers
Cefazolin
Terpolymers
Geometry
Hydrogel
Gelation
Fibroblasts
Vancomycin
Drug delivery
Phase separation
Byproducts
Temperature

Keywords

  • antimicrobials
  • controlled release
  • graft copolymer
  • injectable
  • N-isopropylacrylamide

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

Cite this

In situ forming, resorbable graft copolymer hydrogels providing controlled drug release. / Overstreet, Derek J.; Huynh, Richard; Jarbo, Keith; McLemore, Ryan Y.; Vernon, Brent.

In: Journal of Biomedical Materials Research - Part A, Vol. 101 A, No. 5, 05.2013, p. 1437-1446.

Research output: Contribution to journalArticle

Overstreet, Derek J. ; Huynh, Richard ; Jarbo, Keith ; McLemore, Ryan Y. ; Vernon, Brent. / In situ forming, resorbable graft copolymer hydrogels providing controlled drug release. In: Journal of Biomedical Materials Research - Part A. 2013 ; Vol. 101 A, No. 5. pp. 1437-1446.
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