Delivery of rosiglitazone from an injectable triple interpenetrating network hydrogel composed of naturally derived materials.

Abstract

An in situ gelable and biodegradable triple-interpenetrating network (3XN) hydrogel, completely devoid of potentially cytotoxic extraneous small molecule crosslinkers, is formulated from partially oxidized dextran (Odex), teleostean and N-carboxyethyl chitosan (CEC). Both the rheological profile and mechanical strength of the 3XN hydrogel approximate the combined characteristics of the three individual hydrogels composed of the binary partial formulations (i.e., Odex/CEC, Odex/teleostean, and CEC/teleostean). The 3XN hydrogel is considerably more resistant to fibroblast-mediated degradation compared to each partial formulation in cell culture models; this is attributable to the interpenetrating triple-network structure. The presence of teleostean in the 3XN hydrogel imparts cell affinity, constituting an environment amenable to fibroblast growth. in vivo subdermal injection into mouse model shows that the 3XN hydrogel does not induce extensive inflammatory response nor is there any evidence of tissue necrosis, further confirming the non-cytotoxicity of the hydrogel and its degradation byproducts. Importantly, the capability of the 3XN hydrogel to serve as a sustained drug delivery vehicle is confirmed using rosiglitazone as a model drug. The presence of rosiglitazone profoundly changes the cell/tissue interactions with the subdermally injected 3XN hydrogel. Rosiglitazone suppresses both the inflammatory response and tissue repair in a dose-dependent manner and considerably moderated the hydrogel degradation.