Hydrogels: 3D Drug Delivery Systems for Nanoparticles and Extracellular Vesicles

Abstract

Synthetic and naturally occurring nano-sized particles present versatile vehicles for the delivery of therapy in a range of clinical settings. Their small size and modifiable physicochemical properties support refinement of targeting capabilities, immune response, and therapeutic cargo, but rapid clearance from the body and limited efficacy remain a major challenge. This highlights the need for a local sustained delivery system for nanoparticles (NPs) and extracellular vesicles (EVs) at the target site that will ensure prolonged exposure, maximum efficacy and dose, and minimal toxicity. Biocompatible hydrogels loaded with therapeutic NPs/EVs hold immense promise as cell-free sustained and targeted delivery systems in a range of disease settings. These bioscaffolds ensure retention of the nano-sized particles at the target site and can also act as controlled release systems for therapeutics over a prolonged period of time. The encapsulation of stimuli sensitive components into hydrogels supports the release of the content on-demand. In this review, we highlight the prospect of the sustained and prolonged delivery of these nano-sized therapeutic entities from hydrogels for broad applications spanning tissue regeneration and cancer treatment. Further understanding of the parameters controlling the release rate of these particles and efficient transfer of cargo to target cells will be fundamental to success.

Extracellular Vesicle-Based Hydrogels for Wound Healing Applications

“…Hydrogels are one of the most commonly accepted biomaterials when combined with cell secretions, as they allow the maintenance of biological activity [ 56 ]. In addition, hydrogels resemble human tissues in terms of water absorption capacity, which allows adequate release of therapeutically active particles [ 57 ].…”

Photo‐Controllable Smart Hydrogels for Biomedical Application: A Review

“…[ 159 ] Since the release of these nanofillers into living organisms may result from the biodegradation of PCH‐based nanocomposites through hydrolysis, enzymatic activity, and other aging processes, nanofillers must be biocompatible for biomedical applications. [ 160 ]…”

“…It had a good adsorption capacity of bovine serum protein, cell compatibility, and hemostasis. [ 160 ] The quaternary ammonium and phenolic groups in modified CMCS gave hydrogels excellent antibacterial and antioxidant properties. The produced aldehyde group after UV exposure could offer hydrogel adhesion via Schiff base cross‐linking between the aldehyde group and the amino group at the tissue interface, in addition to forming the hydrogel matrix via imide cross‐linking, so that the hydrogel could be closely adhered to the tissue at the wound site.…”

From Promise to Reality: Bioengineering Strategies to Enhance the Therapeutic Potential of Extracellular Vesicles

“…EVs may even be combined with biomaterials to improve their functional delivery to target tissues. For example, the injection of hydrogels of multiple formulations carrying EVs allowed sustained EV release over time, enhanced local EV retention and improved therapeutic outcomes in different pathological models, both in vitro and in vivo [ 144 ].…”