Issue 33, 2018

P2X7 receptor antagonist delivery vehicle based on photocrosslinked amphiphilic hybrid gels

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.

Graphical abstract: P2X7 receptor antagonist delivery vehicle based on photocrosslinked amphiphilic hybrid gels

Supplementary files

Article information

Article type
Paper
Submitted
15 Febr. 2018
Accepted
11 Maijs 2018
First published
18 Maijs 2018
This article is Open Access
Creative Commons BY license

RSC Adv., 2018,8, 18216-18226

P2X7 receptor antagonist delivery vehicle based on photocrosslinked amphiphilic hybrid gels

D. Aydin and S. Kizilel, RSC Adv., 2018, 8, 18216 DOI: 10.1039/C8RA01460D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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