Injectable Microparticle-Nanoliposome Hydrogel for Extended Release of Small Hydrophilic Molecules

Authors

• Gil Aizik
• Wonmin Choi
• Claire A Ostertag-Hill
• Matthew Torre
• Daniel S Kohane

Language

English

Publication Date

10-21-2025

Journal

ACS Nano

DOI

10.1021/acsnano.5c09484

PMID

41071857

PMCID

PMC12990289

PubMedCentral® Posted Date

3-17-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Achieving sustained local release of small hydrophilic drugs is challenging and is particularly important when the drugs are toxic. To address these challenges, we developed a hybrid system comprising drug-containing microparticles embedded within a nanoliposomal hydrogel matrix. This system forms through salt-induced gelation using physiologically relevant sodium chloride concentrations (0.9%), allowing for microparticle encapsulation without harsh chemical processes. In vitro, the hybrid system exhibited a slower release of encapsulated cargo compared to microparticles or hydrogel alone. In vivo proof of principle was provided with tetrodotoxin (TTX), a small hydrophilic and ultrapotent local anesthetic, which can cause systemic toxicity if the release is not controlled. Encapsulating TTX within the microparticles of the hybrid system provided a very prolonged nerve block (∼100 h), without systemic toxicity. These findings demonstrate that the hybrid system of microparticles within a nanoliposome gel enabled sustained release, improved local drug retention, and provided a safer and prolonged delivery of potent small-molecule therapeutics.

Keywords

Hydrogels, Hydrophobic and Hydrophilic Interactions, Animals, Delayed-Action Preparations, Liposomes, Tetrodotoxin, Drug Liberation, Injections, Particle Size, Mice, Nanoparticles, salt-induced gelation, hybrid gel, controlled release, particle encapsulation, small hydrophilic drug, local drug delivery

Published Open-Access

yes

Recommended Citation

Aizik, Gil; Choi, Wonmin; Ostertag-Hill, Claire A; et al., "Injectable Microparticle-Nanoliposome Hydrogel for Extended Release of Small Hydrophilic Molecules" (2025). Duncan NRI Faculty and Staff Publications. 217.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/217