Supramolecular Hydrogel from Nanoparticles and Cyclodextrins for Local and Sustained Nanoparticle Delivery

Injectable and biodegradable supramolecular hydrogel mPECT NP/alpha-CDgel composed of high-concentration nanoparticle dispersion (<= 20% W/V) and alpha-cyclodextrins (alpha-CD) are prepared by a two-level physical cross-linking using amphiphilic block polymer methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-undecanone) (mPECT) and alpha-CD. The gelation behavior depends on the concentration of nanoparticles and alpha-CD. The viscoelasticity and shear thinning of mPECT NP/alpha-CDgel are confirmed. In vitro hydrogel erosion is demonstrated to be mainly a concentration-dependent dissociation process with general release of discrete mPECT nanoparticles about 50 nm that can be easily taken up by cells. The in vitro release behavior can be modulated by changing the concentration of nanoparticles or alpha-CD. In vitro and in vivo cytotoxicity study demonstrates its biocompatibility and biosafety. Gel formation after subcutaneous injection is also confirmed and mPECT NP/alpha-CDgel shows about 2 weeks retention time. This work validates the potential application for this supramolecular hydrogel in local and sustained delivery of nanoparticles.