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 compare 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.

Evaluation of an In Situ Gelable and Injectable Hydrogel Treatment to Preserve Human Disc Mechanical Function Undergoing Physiologic Cyclic Loading Followed by Hydrated Recovery

“…Sham samples (n ¼ 7) received an injection of the PBS, while the implant group (n ¼ 7) received an injection of the hydrogel implant. The hydrogel implant was created by mixing aqueous solutions of 20% teleostean, 3% N-carboxyethyl chitosan, and 7.5% oxidized dextran were at a ratio of 1:1:2 [15]. Toluidine blue was mixed in the aqueous solution of teleostean before mixing the hydrogel components to permit visualization of the implant.…”

“…In this study, we will be evaluating an in situ gelable, triple-interpenetrating-network hydrogel nucleus replacement. The gel is composed of n-carboxyethyl chitosan, oxidized dextran, and teleostean and is well suited as a nucleus replacement in part because after mixing it solidifies rapidly at body temperature and demonstrates increased resistance to biodegradation relative to single-network hydrogels [15]. It has also recently been demonstrated that the gel maintains cell viability, promotes proliferation, and has mechanical properties similar to native human nucleus pulposus [16].…”

In Vitro Characterization of a Stem-Cell-Seeded Triple-Interpenetrating-Network Hydrogel for Functional Regeneration of the Nucleus Pulposus

“…Previous work has shown that the combination of these materials produces a hydrogel with increased resistance to biodegradation relative to single-network hydrogels, and improved mechanical strength as demonstrated by rheological characterization. 19 Previous work has also shown that in vivo subcutaneous injection of the hydrogel in mice does not induce a significant inflammatory response or evidence of tissue necrosis, suggesting that the hydrogel and its degradation by-products have minimal cytoxicity concerns. 19 The overall objective of this study was to investigate the potential of this hydrogel for NP regeneration.…”

“…This hydrogel is comprised of three naturally derived materials: N-carboxyethyl chitosan, oxidized dextran, and teleostean. 19 Upon mixing, these components rapidly solidify at physiological temperatures in the absence of any extraneous crosslinking agents. Previous work has shown that the combination of these materials produces a hydrogel with increased resistance to biodegradation relative to single-network hydrogels, and improved mechanical strength as demonstrated by rheological characterization.…”

Diabetes Mellitus: A Review on Pathophysiology, Current Status of Oral Pathophysiology, Current Status of Oral Medications and Future Perspectives

“…Further, an in-situ injectable and biodegradable triple-interpenetrating network (3XN) hydrogel, was developed in order to deliver rosiglitazone which was comprised from dextran, teleostean and N-carboxyethyl chitosan. The dissolution ability was reported as sustained for the model drug 63 .…”