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Hydrogels for the Delivery of Plant-Derived (Poly)Phenols.

ABSTRACT: This review deals with hydrogels as soft and biocompatible vehicles for the delivery of plant-derived (poly)phenols, compounds with low general toxicity and an extraordinary and partially unexplored wide range of biological properties, whose use presents some major issues due to their poor bioavailability and water solubility. Hydrogels are composed of polymeric networks which are able to absorb large amounts of water or biological fluids while retaining their three-dimensional structure. Apart from this primary swelling capacity, hydrogels may be easily tailored in their properties according to the chemical structure of the polymeric component in order to obtain smart delivery systems that can be responsive to various internal/external stimuli. The functionalization of the polymeric component of hydrogels may also be widely exploited to facilitate the incorporation of bioactive compounds with different physicochemical properties into the system. Several prototype hydrogel systems have been designed for effective polyphenol delivery and potential employment in the treatment of human diseases. Therefore, the inherent features of hydrogels have been the focus of considerable research efforts over the past few decades. Herein, we review the most recent advances in (poly)phenol-loaded hydrogels by analyzing them primarily from the therapeutic perspective and highlighting the innovative aspects in terms of design and chemistry.

SUBMITTER: Micale N

PROVIDER: S-EPMC7397257 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Hydrogels for the Delivery of Plant-Derived (Poly)Phenols.

Micale Nicola N Citarella Andrea A Molonia Maria Sofia MS Speciale Antonio A Cimino Francesco F Saija Antonella A Cristani Mariateresa M

Molecules (Basel, Switzerland) 20200716 14

This review deals with hydrogels as soft and biocompatible vehicles for the delivery of plant-derived (poly)phenols, compounds with low general toxicity and an extraordinary and partially unexplored wide range of biological properties, whose use presents some major issues due to their poor bioavailability and water solubility. Hydrogels are composed of polymeric networks which are able to absorb large amounts of water or biological fluids while retaining their three-dimensional structure. Apart ...[more]

PMID: 32708833

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Project description:Recently, biomaterials have been designed to contain redox-sensitive moieties, such as thiols and disulfides, to impart responsive degradation and/or controlled release. However, due to the high sensitivity of cellular redox-based systems which maintain free-radical homeostasis (e.g. glutathione/glutathione disulfide), if these biomaterials modify the cellular redox environment, they may inadvertently affect cellular compatibility and/or oxidative stress defenses. In this work, we hypothesize that the degradation products of a poly(β-amino ester) (PBAE) hydrogel formed with redox sensitive disulfide (cystamine) crosslinking could serve as a supplement to the environmental cellular antioxidant defenses. Upon introduction into a reducing environment, these disulfide-containing hydrogels cleave to present bound-thiol groups, yet remain in the bulk form at up to 66 mol% cystamine of the total amines. By controlling the molar fraction of cystamine, it was apparent that the thiol content varied human umbilical vein endothelial cell (HUVEC) viability IC50 values across an order of magnitude. Further, upon introduction of an enzymatic oxidative stress generator to the cell culture (HX/XO), pre-incubated thiolated hydrogel degradation products conferred cellular and mitochondrial protection from acute oxidative stress, whereas non-reduced disulfide-containing degradation products offered no protection. This polymer may be an advantageous implantable drug delivery system for use in acute oxidative stress prophylaxis and/or chronic oxidative stress cell therapies due to its solid/liquid reversibility in a redox environment, controlled thiolation, high loading capacity through covalent drug-addition, and simple post-synthesis modification which bound-thiols introduce. STATEMENT OF SIGNIFICANCE:In this work, we demonstrate a unique property of disulfide containing degradable biomaterials. By changing the redox state of the degradation products (from oxidized to reduced), it is possible to increase the IC50 of the material by an order of magnitude. This dramatic shift is linked directly to the oxidative stress response of the cells and suggests a possible mechanism by which one can tune the cellular response to degradable biomaterials.

Dataset Information

Hydrogels for the Delivery of Plant-Derived (Poly)Phenols.

Publications

Hydrogels for the Delivery of Plant-Derived (Poly)Phenols.

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