Hydrogels and Organogels for Local Anesthetic Delivery: Advances, Challenges, and Translational Perspectives

TL;DR

This paper reviews how gels can be used to deliver local anesthetics more effectively and safely by extending their action at the site of use.

Contribution

The paper introduces a framework for selecting gel-based anesthetic depots based on drug chemistry, anatomy, and clinical goals.

Findings

Hydrogels enable sustained analgesia in various anatomical settings through tunable release mechanisms.

Organogels are effective for lipophilic anesthetics in outpatient and chronic pain applications.

Bigels offer dual-solubilization but lack in vivo validation for anesthetic delivery.

Abstract

Gel-based depots are increasingly recognized as platforms to extend the intratissue residence of local anesthetics (LAs) while reducing systemic exposure. Hydrogels, organogels, and emerging bigels represent three distinct architectures defined by their continuous phases and drug–matrix interactions. Hydrogels provide hydrated polymer networks with predictable injectability, tunable degradation, and diffusion- or stimulus-responsive release, enabling sustained analgesia in perineural, peri-incisional, intra-articular, and implant-adjacent settings. Organogels, formed by supramolecular assembly of low-molecular-weight gelators in lipids or semi-polar solvents, strongly solubilize lipophilic LA bases and enhance barrier partitioning, making them suitable for dermal, transdermal, and mucosal applications in outpatient or chronic pain care. Bigels integrate aqueous and lipid domains within biphasic matrices, improving rheology, spreadability, and dual-solubilization capacity, although their use in LA delivery remains at the formulation stage, with no validated in vivo pharmacology. This narrative review synthesizes the design principles, release mechanisms, and translational evidence across these platforms, highlighting domain-specific advantages and barriers related to mechanical robustness, sterilization, reproducibility, and regulatory feasibility. We propose a platform-level framework in which depot selection is aligned with LA chemistry, anatomical context, and clinical objectives to guide the development of workflow-compatible next-generation LA depots.

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