An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate

Pritchard, Christopher; O’Shea, Timothy M.; Siegwart, Daniel J.; Calo, Eliezer; Anderson, Daniel G.; Reynolds, Francis M.; Thomas, John A.; Slotkin, Jonathan R.; Woodard, Eric J.; Langer, Róbert

doi:10.1016/j.biomaterials.2010.08.106

Cited by 142 publications

(119 citation statements)

References 40 publications

Supporting

Mentioning

116

Contrasting

Order By: Relevance

“…This polymer was proposed for use in injectable drug formulations [15]. We were interested in the performance of the enzyme under non-buffered conditions at room temperature.…”

Section: Discussionmentioning

confidence: 99%

“…The thiol-acrylate hydrogel was originally proposed as a base-catalyzed polymerization for injectable drug formulations [15] and this recipe was subsequently modified to obtain gelation after a programmable time lag using the increase in pH of the urea-urease reaction [9]. Here we further modified the formulation with the addition of PVA in order to obtain gel beads using emulsion polymerisation.…”

Section: Thiol-acrylate Hydrogel Beadsmentioning

confidence: 99%

“…In order to circumvent the latter, hydrogels with more open structures may be used. Here we investigated the employment of a novel thiolacrylate hydrogel [15] for immobilization of the enzyme urease. The mm-sized hydrogel beads were prepared using emulsion polymerization and the catalytic activity and stability of the urease beads was compared to solution phase experiments.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Kinetics of the urea–urease clock reaction with urease immobilized in hydrogel beads

Bubanja

Bánsági

Taylor

2017

Reac Kinet Mech Cat

View full text Add to dashboard Cite

Feedback driven by enzyme catalyzed reactions occurs widely in biology and has been well characterized in single celled organisms such as yeast. There are still few examples of robust enzyme oscillators in vitro that might be used to study nonlinear dynamical behavior. One of the simplest is the urea-urease reaction that displays autocatalysis driven by the increase in pH accompanying the production of ammonia. A clock reaction was obtained from low to high pH in batch reactor and bistability and oscillations were reported in a continuous flow rector. However, the oscillations were found to be irreproducible and one contributing factor may be the lack of stability of the enzyme in solution at room temperature. Here, we investigated the effect of immobilizing urease in thiol-poly(ethylene glycol) acrylate (PEGDA) hydrogel beads, prepared using emulsion polymerization, on the ureaurease reaction. The resultant mm-sized beads were found to reproduce the pH clock and, under the conditions employed here, the stability of the enzyme was increased from hours to days.

show abstract

“…This polymer was proposed for use in injectable drug formulations [15]. We were interested in the performance of the enzyme under non-buffered conditions at room temperature.…”

Section: Discussionmentioning

confidence: 99%

Section: Thiol-acrylate Hydrogel Beadsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Kinetics of the urea–urease clock reaction with urease immobilized in hydrogel beads

Bubanja

Bánsági

Taylor

2017

Reac Kinet Mech Cat

View full text Add to dashboard Cite

show abstract

“…A similar PEG‐based hydrogel to the one constructed in this study was demonstrated to undergo hydrolytic degradation over the course of weeks, thus resulting in controlled drug release 23. More recently, a method for the pH control of the self‐assembly and disassembly of peptide hydrogels was proposed for fluidic guidance in channels and self‐erasing rapid prototyping 28…”

mentioning

confidence: 83%

Temporal Control of Gelation and Polymerization Fronts Driven by an Autocatalytic Enzyme Reaction

et al. 2016

View full text Add to dashboard Cite

Chemical systems that remain kinetically dormant until activated have numerous applications in materials science. Herein we present a method for the control of gelation that exploits an inbuilt switch: the increase in pH after an induction period in the urease‐catalyzed hydrolysis of urea was used to trigger the base‐catalyzed Michael addition of a water‐soluble trithiol to a polyethylene glycol diacrylate. The time to gelation (minutes to hours) was either preset through the initial concentrations or the reaction was initiated locally by a base, thus resulting in polymerization fronts that converted the mixture from a liquid into a gel (ca. 0.1 mm min−1). The rate of hydrolytic degradation of the hydrogel depended on the initial concentrations, thus resulting in a gel lifetime of hours to months. In this way, temporal programming of gelation was possible under mild conditions by using the output of an autocatalytic enzyme reaction to drive both the polymerization and subsequent degradation of a hydrogel.

show abstract

“…A custom made two component cross-linked hydrogel (PEG) consisting of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PBS) was prepared by mixing PEGDA in PBS into ETTMP-1300 in PBS [30]. PEG is a synthetic water-soluble polymer approved by the FDA for biomedical use in different applications including injectable hydrogels.…”

Section: Gelsmentioning

confidence: 99%

A new model for in vitro testing of vitreous substitute candidates

Barth

Crafoord

O’Shea

et al. 2014

Graefes Arch Clin Exp Ophthalmol

Self Cite

View full text Add to dashboard Cite

Purpose To describe a new model for in vitro assessment of novel vitreous substitute candidates. Methods The biological impact of three vitreous substitute candidates was explored in a retinal explant culture model; a polyalkylimide hydrogel (Bio-Alcamid®), a two component hydrogel of 20 wt.% poly (ethylene glycol) in phosphate buffered saline (PEG) and a cross-linked sodium hyaluronic acid hydrogel (Healaflow®). The gels where applied to explanted adult rat retinas and then kept in culture for 2, 5 and 10 days. Gel-exposed explants were compared with explants incubated under standard tissue culture conditions. Cryosections of the specimens were stained with hematoxylin and eosin, immunohistochemical markers (GFAP, Vimentin, Neurofilament 160, PKC, Rhodopsin) and TUNEL. Results Explants kept under standard conditions as well as PEG-exposed explants displayed disruption of retinal layers with moderate pyknosis of all neurons. They also displayed moderate labeling of apoptotic cells. Bio-Alcamid®-exposed explants displayed severe thinning and disruption of retinal layers with massive cell death. Healaflow®-treated explants displayed normal retinal lamination with significantly better preservation of retinal neurons compared with control specimens, and almost no signs of apoptosis. Retinas exposed to Healaflow® and retinas kept under standard conditions showed variable labeling of GFAP with generally low expression and some areas of upregulation. PEG-exposed retinas showed increased GFAP labeling and Bio-Alcamid®-exposed retinas showed sparse labeling of GFAP. Conclusions Research into novel vitreous substitutes has important implications for both medical and surgical vitreoretinal disease. The in vitro model presented here provides a method of biocompatibility testing prior to more costly and cumbersome in vivo experiments. The explant culture system imposes reactions within the retina including disruption of layers, cell death and gliosis, and the progression of these reactions can be used for comparison of vitreous substitute candidates. Bio-Alcamid® had strong adverse effects on the retina which is consistent with results of prior in vivo trials. PEG gel elicits reactions similar to the control retinas whereas Healaflow® shows protection from culture-induced trauma indicating favorable biocompatibility.

show abstract

An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate

Cited by 142 publications

References 40 publications

Kinetics of the urea–urease clock reaction with urease immobilized in hydrogel beads

Kinetics of the urea–urease clock reaction with urease immobilized in hydrogel beads

Temporal Control of Gelation and Polymerization Fronts Driven by an Autocatalytic Enzyme Reaction

A new model for in vitro testing of vitreous substitute candidates

Contact Info

Product

Resources

About