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Thermogelling, ABC Triblock Copolymer Platform for Resorbable Hydrogels with Tunable, Degradation‐Mediated Drug Release

Gupta, Mukesh K. ; Martin, John R. ; Dollinger, Bryan R. ; Hattaway, Madison E. ; Duvall, Craig L.

Advanced functional materials, 2017-12, Vol.27 (47), p.n/a [Periódico revisado por pares]

Germany: Wiley Subscription Services, Inc

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  • Título:
    Thermogelling, ABC Triblock Copolymer Platform for Resorbable Hydrogels with Tunable, Degradation‐Mediated Drug Release
  • Autor: Gupta, Mukesh K. ; Martin, John R. ; Dollinger, Bryan R. ; Hattaway, Madison E. ; Duvall, Craig L.
  • Assuntos: Ambient temperature ; Block copolymers ; Chemical synthesis ; controlled drug release ; Copolymers ; Crosslinking ; Degradation ; Drug delivery systems ; Forming ; Formulations ; Hydrogels ; hydrolytic degradation ; in situ forming hydrogels ; injectable thermoresponsive biomaterials ; Isopropylacrylamide ; Materials science ; Micelles ; Oxidation ; Polymers ; Propylene ; reactive oxygen species (ROS) responsive polymer
  • É parte de: Advanced functional materials, 2017-12, Vol.27 (47), p.n/a
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.201704107.
  • Descrição: Clinical application of injectable, thermoresponsive hydrogels is hindered by lack of degradability and controlled drug release. To overcome these challenges, a family of thermoresponsive, ABC triblock polymer‐based hydrogels has been engineered to degrade and release drug cargo through either oxidative or hydrolytic/enzymatic mechanisms dictated by the “A” block composition. Three ABC triblock copolymers are synthesized with varying “A” blocks, including oxidation‐sensitive poly(propylene sulfide), slow hydrolytically/enzymatically degradable poly(ε‐caprolactone), and fast hydrolytically/enzymatically degradable poly(d,l‐lactide‐co‐glycolide), forming the respective formulations PPS135‐b‐PDMA152‐b‐PNIPAAM225 (PDN), PCL85‐b‐PDMA150‐b‐PNIPAAM150 (CDN), and PLGA60‐b‐PDMA148‐b‐PNIPAAM152 (LGDN). For all three polymers, hydrophilic poly(N,N‐dimethylacrylamide) and thermally responsive poly(N‐isopropylacrylamide) comprise the “B” and “C” blocks, respectively. These copolymers form micelles in aqueous solutions at ambient temperature that can be preloaded with small molecule drugs. These solutions quickly transition into hydrogels upon heating to 37 °C, forming a supra‐assembly of physically crosslinked, drug‐loaded micelles. PDN hydrogels are selectively degraded under oxidative conditions while CDN and LGDN hydrogels are inert to oxidation but show differential rates of hydrolytic/enzymatic decomposition. All three hydrogels are cytocompatible in vitro and in vivo, and drug‐loaded hydrogels demonstrate differential release kinetics in vivo corresponding with their specific degradation mechanism. These collective data highlight the potential cell and drug delivery use of this tunable class of ABC triblock polymer thermogels. Two‐stage assembly, ABC triblock polymer‐based, thermally responsive hydrogel formulations are engineered to degrade through either ROS or hydrolytic mechanisms based on composition of hydrophobic “A” block. In vitro and in vivo drug release kinetics from these hydrogels correlate to their respective degradation mechanism/susceptibility and enable tailoring of release profiles for drug delivery and tissue regenerative applications.
  • Editor: Germany: Wiley Subscription Services, Inc
  • Idioma: Inglês
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