In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery.

Advances in hydrogel technology have unlocked unique and valuable capabilities that are being applied to a diverse set of translational applications. Hydrogels perform functions relevant to a range of biomedical purposes-they can deliver drugs or cells, regenerate hard and soft tissues, adhere to wet tissues, prevent bleeding, provide contrast during imaging, protect tissues or organs during radiotherapy, and improve the biocompatibility of medical implants. These capabilities make hydrogels useful for many distinct and pressing diseases and medical conditions and even for less conventional areas such as environmental engineering. In this review, we cover the major capabilities of hydrogels, with a focus on the novel benefits of injectable hydrogels, and how they relate to translational applications in medicine and the environment. We pay close attention to how the development of contemporary hydrogels requires extensive interdisciplinary collaboration to accomplish highly specific and complex biological tasks that range from cancer immunotherapy to tissue engineering to vaccination. We complement our discussion of preclinical and clinical development of hydrogels with mechanical design considerations needed for scaling injectable hydrogel technologies for clinical application. We anticipate that readers will gain a more complete picture of the expansive possibilities for hydrogels to make practical and impactful differences across numerous fields and biomedical applications.

Translational Applications of Hydrogels.

Human gene therapy

Injectable biodegradable copolymer hydrogels, which exhibit a sol-gel phase transition in response to external stimuli, such as temperature changes or both pH and temperature (pH/temperature) alterations, have found a number of uses in biomedical and pharmaceutical applications, such as drug delivery, cell growth, and tissue engineering. These hydrogels can be used in simple pharmaceutical formulations that can be prepared by mixing the hydrogel with drugs, proteins, or cells. Such formulations are administered in a straightforward manner, through site-specific control of release behavior, and the hydrogels are compatible with biological systems. This review will provide a summary of recent progress in biodegradable temperature-sensitive polymers including polyesters, polyphosphazenes, polypeptides, and chitosan, and pH/temperature-sensitive polymers such as sulfamethazine-, poly(beta-amino ester)-, poly(amino urethane)-, and poly(amidoamine)-based polymers. The advantages of pH/temperature-sensitive polymers over simple temperature-sensitive polymers are also discussed. A perspective on the future of injectable biodegradable hydrogels is offered.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/mabi.200900402

Injectable Biodegradable Hydrogels

Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel.

Purpose. Currently, most pDNA delivery systems based on synthetic polymers are either nonbiodegradable or not sensitive to the release environment. The primary objective of this study was to develop and evaluate an aqueous-based, thermosensitive, biodegradable and biocompatible triblock copolymer to control pDNA delivery in vitro and in vivo. 
Methods. The triblock copolymers, poly[ethylene glycol-b-(D, L-lactic acid-co-glycol acid)-b-ethylene glycol] (PEG-PLGA-PEG), were synthesized as previously described. The molecular weight and polydispersity of PEG-PLGA-PEG were monitored by gel permeation chromatography (GPC). The cytotoxicity of PEG-PLGA-PEG was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra- zolium bromide assay. The release of 32P-labeled pDNA entrapped in aqueous dispersion of PEG-PLGA-PEG in 0.1 mol/L sodium phosphate buffer solution (pH 7.4) was studied at 37°C under agitation. Gene transfection efficiency was evaluated in a skin wound model in CD-1 mice. 
Results. The aqueous dispersion of PEG-PLGA-PEG flows freely at room temperature but form a gel at 37°C body temperature. The in vitro degradation of PEG-PLGA-PEG lasted for more than 30 days. The cytotoxicity of PEG-PLGA-PEG evaluated in HEK 293 cells was significantly lower than that of poly-L-lysine hydrochloride. The release profile of supercoiled pDNA from the polymer followed the zero-order kinetics up to 12 days. Maximal gene expression of luciferase was at 24 h in the skin wound of CD-1 mice and by 72 h, the expression dropped by nearly 94%. 
Conclusions. These results suggest hydrogel formed by PEG-PLGA-PEG could be a promising platform for delivery of pDNA, which represents a novel strategy that may serve as a non-viral vector for gene therapy in wound healing.

Controlled gene delivery system based on thermosensitive biodegradable hydrogel.

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Controlled gene delivery system based on thermosensitive biodegradable hydrogel.