Cell Protective, ABC Triblock Polymer-Based Thermoresponsive Hydrogels with ROS-Triggered Degradation and Drug Release

Abstract

A combination of anionic and RAFT polymerization was used to synthesize an ABC triblock polymer poly[(propylenesulfide)-block-(N,N-dimethylacrylamide)-block-(N-isopropylacrylamide)] (PPS-b-PDMA-b-PNIPAAM) that forms physically cross-linked hydrogels when transitioned from ambient to physiologic temperature and that incorporates mechanisms for reactive oxygen species (ROS) triggered degradation and drug release. At ambient temperature (25 °C), PPS-b-PDMA-b-PNIPAAM assembled into 66 ± 32 nm micelles comprising a hydrophobic PPS core and PNIPAAM on the outer corona. Upon heating to physiologic temperature (37 °C), which exceeds the lower critical solution temperature (LCST) of PNIPAAM, micelle solutions (at ≥2.5 wt %) sharply transitioned into stable, hydrated gels. Temperature-dependent rheology indicated that the equilibrium storage moduli (G') of hydrogels at 2.5, 5.0, and 7.5 wt % were 20, 380, and 850 Pa, respectively. The PPS-b-PDMA-b-PNIPAAM micelles were preloaded with the model drug Nile red, and the resulting hydrogels demonstrated ROS-dependent drug release. Likewise, exposure to the peroxynitrite generator SIN-1 degraded the mechanical properties of the hydrogels. The hydrogels were cytocompatible in vitro and were demonstrated to have utility for cell encapsulation and delivery. These hydrogels also possessed inherent cell-protective properties and reduced ROS-mediated cellular death in vitro. Subcutaneously injected PPS-b-PDMA-b-PNIPAAM polymer solutions formed stable hydrogels that sustained local release of the model drug Nile red for 14 days in vivo. These collective data demonstrate the potential use of PPS-b-PDMA-b-PNIPAAM as an injectable, cyto-protective hydrogel that overcomes conventional PNIPAAM hydrogel limitations such as syneresis, lack of degradability, and lack of inherent drug loading and environmentally responsive release mechanisms.

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

“…[11] This material was based on the ABC triblock copolymer poly(propylene sulfide)- b -poly( N , N -dimethylacrylamide)- b -poly( N -isopropylacrylamide), abbreviated PDN. This linear polymer self-assembles into micellar nanoparticles in an aqueous solution at room temperature, and the resultant particles supra-assemble into stable, nonsyneresing hydrogels at physiological temperature.…”

Reactive Oxygen Species (ROS) Responsive Polymers for Biomedical Applications

“…Duvall and co-workers developed an ABC triblock polymer-based thermoresponsive hydrogels with ROS-triggered degradation property. [ 66 ] The poly[(propylenesulfi de)-block-(N,N-dimethylacylamide)-block-(N-isopropylacrylamide)] (PPS 60 -b-PDMA 150 -b-PNIPAAM 150 ) self-assembled into micelles at room temperature and transferred to hydrogels as the temperature increased above the LCST of the PNIPAM block. When exposed to ROS, the PPS block became hydrophilic, leading Figure 6.…”

Evaluating a simple blending approach to prepare magnetic and stimuli-responsive composite hydrogel particles for application in biomedical field

“…The produced Fe 3 O 4 particles were repeatedly washed by magnetic separation and subsequent redispersion in deionized distilled water to remove salt and excess stabilizer. 2 nanocomposite particles At first 50 g ethanol, 1.0 g deionized water and 2.38 g NH 4 OH were taken in a three necked flask under vigorous stirring, then 1.56 g TEOS was charged into the above mixture and the flask was heated to 40°C gradually in a hot water bath with constant stirring at 300 rpm. 20 min later water-based 0.44 g magnetic (Fe 3 O 4 ) fluid containing 0.025 g solid was added into the above mixture and the process was continued for 30 min.…”

“…Stimuli-responsive hydrogels known as smart materials are macromolecules that undergo reversible volume phase transition in response to a small change of external stimuli such as temperature [1][2][3][4][5][6][7][8][9], pH [9][10][11][12][13], light [14][15][16], electric current [17][18][19], ionic strength [20][21][22] or chemical species [23]. Researchers are showing much attention in these materials for their wide range of biomedical and pharmaceutical applications [24][25][26][27][28][29].…”

“…MMA/MAA was added to improve the solubility of styrene in the aqueous dispersion media for facilitating smooth copolymerization with NIPAM as the latter in absence of MMA/MAA may produce larger proportion of water soluble homopolymer due to its comparatively high reaction rate. The hydrophobichydrophobic interactions among hydrophobic PS-PMMA or PS segments in the prepared conetworks are expected to form microgels in water, a phenom-enon generally observed for amphiphilic copolymer networks consisting of hydrophilic and hydrophobic polymer segments [60][61][62][63][64] 4 OH and other chemicals were of analytical grade. Ethanol and deionized water was distilled using a glass (Pyrex) distillation apparatus.…”