Hydrogels have increasingly received considerable attention for local opioids delivery in order to sustained wound pain relief. However, burst release of drugs is a critical problem of hydrogels. To this aim, a local drug delivery system consisting of polycaprolactone (PCL) microspheres containing methadone hydrochloride/polyethylene glycol (PEG)-based hydrogels were developed to prolong drug release with potential utilization in pain treatment. Four different drug delivery systems, including methadone hydrochloride/PEG-(N-3)(4)-based hydrogel, methadone hydrochloride/PEG-(N-3)(2)-based hydrogel, methadone hydrochloride/PCL/PEG-(N-3)(4), and methadone hydrochloride/PCL/PEG-(N-3)(2) composite hydrogels, were fabricated to investigate drug release profiles of these systems. The results showed that drug released can be controlled by both the double-barrier matrix (hydrogel/microsphere), and the crosslinking density of hydrogels. Therefore, methadone hydrochloride/PCL/PEG-(N-3)(2) composite hydrogel with high crosslinking density has great potential application in sustained release systems for wound pain relief. (c) 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48967.
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