Journal
BIOMACROMOLECULES
Volume 19, Issue 6, Pages 2238-2247Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.8b00301
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Funding
- Japan Society for the Promotion of Science (JSPS
- JSPS KAKENHI Grant) [16H05910]
- JSPS (JSPS KAKENHI Grant) [16H01852]
- JSPS [16J09364]
- cooperative project among medicine, dentistry, and engineering for medical innovation Construction of creative scientific research of the viable material via integration of biology and engineering from Ministry of Education, Culture, Sports, Science and
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In prior research it has been demonstrated that methylated beta-cyclodextrins-threaded acid-labile polyrotaxanes (Me-PRXs) exhibit a lower critical solution temperature (LCST) and form coacervate droplets above their LCST. In this study, the encapsulation of proteins in coacervate droplets and the pH-responsive release of proteins, through the acid-induced dissociation of the Me-PRX, were investigated. The coacervate droplets encapsulate various proteins, such as bovine serum albumin (BSA), lysozyme, and beta-galactosidase, at pH 7.4, into their hydrophobic inner phase. Concomitant with the pH dependent dissociation of the Me-PRXs, the coacervates degraded below pH 6.5 and released encapsulated proteins, with the intrinsic activity of proteins maintained. Additionally, the subcutaneous injection of coacervate droplets encapsulating BSA in mice revealed that the retention time of the BSA at the injection site was prolonged compared to that of free BSA. Altogether, the coacervate droplets of the Me-PRX would be utilized as a new class of pH-responsive and injectable carrier for the controlled release of therapeutic proteins.
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