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Thermoresponsive nanogels for prolonged duration local anesthesia.

ABSTRACT: Nanogels based on poly(N-isopropylacrylamide) are attractive vehicles for prolonged duration local anesthesia because of their tunable size, number of functional groups, thermoresponsiveness and anionic charge. Nerve block durations of up to 9h were achieved using acrylic acid-loaded nanogels loaded with bupivacaine. Increasing the anionic charge density of the nanogels or (for more highly acid-functionalized nanogels) decreasing the nanogel size facilitated longer duration of anesthetic release. Small (<300 nm diameter) nanogels formed dense aggregates upon injection in vivo and induced only mild inflammatory responses, while large (>500 nm diameter) nanogels typically remained as liquid-like residues in vivo and induced more severe inflammatory reactions.

SUBMITTER: Hoare T

PROVIDER: S-EPMC3429626 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Thermoresponsive nanogels for prolonged duration local anesthesia.

Hoare Todd T Young Stuart S Lawlor Michael W MW Kohane Daniel S DS

Acta biomaterialia 20120623 10

Nanogels based on poly(N-isopropylacrylamide) are attractive vehicles for prolonged duration local anesthesia because of their tunable size, number of functional groups, thermoresponsiveness and anionic charge. Nerve block durations of up to 9h were achieved using acrylic acid-loaded nanogels loaded with bupivacaine. Increasing the anionic charge density of the nanogels or (for more highly acid-functionalized nanogels) decreasing the nanogel size facilitated longer duration of anesthetic release ...[more]

PMID: 22732383

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Project description:Soft nanoparticles are interesting materials due to their size, deformability, and ability to host guest molecules. Surface properties play an essential role in determining the fate of the particles in biological medium, and coating of the nanoparticles (and polymers) with carbohydrates has been found to be an efficient strategy for increasing their biocompatibility and fine-tuning other important properties such as aqueous solubility. In this work, soft nanogels of poly(N-vinylcaprolactam), PNVCL, were surface-functionalized with different glucose and maltose ligands, and the colloidal properties of the gels were analyzed. The PNVCL nanogels were first prepared via semibatch precipitation polymerization, where a comonomer, propargyl acrylate (PA), was added after preparticle formation. The aim was to synthesize "clickable" nanogels with alkyne groups on their surfaces. The nanogels were then functionalized with two separate azido-glucosides and azido-maltosides (containing different linkers) through a copper-catalyzed azide-alkyne cycloaddition (CuAAc) click reaction. The glucose and maltose bearing nanogels were thermoresponsive and shrank upon heating. Compared to the PNVCL-PA nanogel, the carbohydrate bearing ones were larger, more hydrophilic, had volume phase transitions at higher temperatures, and were more stable against salt-induced precipitation. In addition to investigating the colloidal properties of the nanogels, the carbohydrate recognition was addressed by studying the interactions with a model lectin, concanavalin A (Con A). The binding efficiency was not affected by the temperature, which indicates that the carbohydrate moieties are located on the gel surfaces, and are capable of interacting with other biomolecules independent of temperature. Thus, the synthesis produces nanogels, which have surface functions capable of biorelevant interactions and a thermoresponsive structure. These types of particles can be used for drug delivery.

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Thermoresponsive nanogels for prolonged duration local anesthesia.

Publications

Thermoresponsive nanogels for prolonged duration local anesthesia.

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