Abstract
We report here a method for the synthesis of a unique hybrid gel system for the sustained delivery of P2X7 receptor (P2X7R) antagonist. P2X7R has been reported as a key mediator in inflammatory processes and controlled delivery of this molecule would be critical for the treatment of inflammatory arthritis. The hybrid gel designed here for the sustained delivery of P2X7R antagonists is based on crosslinked hydrophobic styrene-butadiene-styrene (SBS) polymer as a continuous network, where hydrogel particles prepared with hydrophilic poly(ethylene glycol) (PEG) were embedded into this system. PEG hydrogel particle-incorporated SBS gels were characterized through electron microscopy, water contact angle observations, and strong mechanical properties were confirmed through nanoindentation measurements. The release of P2X7R antagonist from these hybrid hydrogel-elastomer system demonstrated a sustained drug release profile up to 28 days at physiological pH, which was not observed in earlier reports. We obtained drug release percentages ranging from 49.72% to 93.04% which indicated the tunability of release through SBS crosslinking and hydrophilic/hydrophobic nature of SBS. This tunability is significant to achieve simultaneous improvements in drug efficacy with reduced side effects. CellTiter-Glo luminescence measurements using human kidney cells revealed that these networks are non-toxic and highly biocompatible with percent cell viabilities of higher than 85%. The approach presented here with crosslinked, amphiphilic and elastic SBS gel systems is not only promising for extended release of P2X7R antagonist but could also allow for incorporation of different molecules so that simultaneous/sequential and extended release profiles for therapeutic molecules could be achieved.
Highlights
SBS is commonly used as a rubber substitute due to its desirable properties such as high tensile strength and elasticity properties.[1,2] It is a synthetic triblock copolymer composed of long chains of polybutadiene and polystyrene
Size of the dispersed droplets in particle stabilized poly(ethylene glycol) (PEG)-cyclohexane emulsions were adjusted with 1.5% nanoparticle concentration where vortex durations of 30 s, 60 s, 2 min and 8 min were used for optimization experiments
We developed a novel crosslinked SBS hybrid gels incorporating PEG microparticle platform for sustained delivery of an antirheumatoid arthritis drug
Summary
SBS is commonly used as a rubber substitute due to its desirable properties such as high tensile strength and elasticity properties.[1,2] It is a synthetic triblock copolymer composed of long chains of polybutadiene and polystyrene. Polystyrene is tough and this contributes to the durability of SBS, while polybutadiene brings rubber-like properties to SBS. SBS has been used in a variety of industries where durability is important, such as building materials (as an additive to bitumen to improve mechanical properties of roads), shoes, tire treads, biomedical devices and other places. SBS can be crosslinked to create slightly hydrophobic networks through thiol–ene photopolymerization.[6,7,8] Crosslinked SBS can be synthesized through the addition of radicalized thiol groups onto double bonds present in poly(butadiene blocks). Vincristine, 18216 | RSC Adv., 2018, 8, 18216–18226
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