Degradable and Injectable Hydrogel for Drug Delivery in Soft Tissues

摘要

Injectable hydrogels are promising platforms for tissue engineering and local drug delivery as they allow minimal invasiveness. We have here developed an injectable and biodegradable hydrogel based on an amphiphilic PNIPAAm-b-PLA-b-PEG-b-PLA-b-PNIPAAm pentablock copolymer synthesized by ring-opening polymerization/nitroxide-mediated polymerization (ROP/NMP) combination. The hydrogel formation at around 30 degrees C was demonstrated to be mediated by intermicellar bridging through the PEG central block. Such a result was particularly highlighted by the inability of a PEG-b-PLA-b-PNIPAAm triblock analog of the same composition to gelify. The hydrogels degraded through hydrolysis of the PLA esters until complete mass loss due to the diffusion of the recovered PEG and PNIPAAm/micelle based residues in the solution. Interestingly, hydrophobic molecules such as riluzole (neuroprotective drug) or cyanine 5.5 (imaging probe) could be easily loaded in the hydrogels' micelle cores by mixing them with the copolymer solution at room temperature. Drug release was correlated to polymer mass loss. The hydrogel was shown to be cytocompatible (neuronal cells, in vitro) and injectable through a small-gauge needle (in vivo in rats). Thus, this hydrogel platform displays highly attractive features for use in brain/soft tissue engineering as well as in drug delivery.