Light activated pulsatile drug delivery for prolonged peripheral nerve block.

Area of Science:

• Biomedical Engineering
• Materials Science
• Anesthesiology

Background:

• Regional anesthesia, including peripheral nerve blocks and neuraxial anesthesia, is crucial for reducing systemic side effects and recovery times.
• A key limitation of current regional anesthesia techniques is the short duration of action for single-injection methods.
• There is a need for advanced drug delivery systems that can provide prolonged and controlled anesthetic effects.

Purpose of the Study:

• To develop a thermoresponsive nanogel capable of controlled, long-lasting anesthetic drug release.
• To investigate the use of near-infrared light for external activation and triggering of drug release.
• To evaluate the in vivo efficacy and safety of the nanogel system for prolonged regional anesthesia.

Main Methods:

• Development of a thermoresponsive nanogel composed of poly(oligoethylene glycol methacrylate) incorporating hollow gold nanoparticles.
• Encapsulation of the long-lasting anesthetic bupivacaine within the nanogel matrix.
• External activation of drug release using near-infrared light, leveraging the photothermal properties of gold nanoparticles for controlled temperature elevation.
• In vitro assessment of drug release kinetics, including repeated triggering and pulsatile release.
• In vivo evaluation of the anesthetic duration and tissue toxicity using a sciatic nerve block model in animals.

Main Results:

• The developed nanogel demonstrated controlled, pulsatile release of bupivacaine triggered by near-infrared light-induced photothermal effect.
• In vivo studies showed that the nanogel significantly prolonged the anesthetic effect of bupivacaine for over 6 hours, compared to 2 hours for free bupivacaine.
• The release system was repeatedly activated by subsequent irradiation cycles without causing detrimental toxicity in the infiltrated tissues.
• The nanogel system achieved spatio-temporal control over drug release due to its reversible thermosensitive nature.

Conclusions:

• The thermoresponsive nanogel system offers a promising platform for achieving prolonged regional anesthesia with externally controlled drug release.
• This technology has the potential to enhance patient outcomes by extending the duration of pain relief and reducing the need for repeated administrations.
• The ability to repeatedly trigger drug release without toxicity suggests significant clinical applicability for advanced pain management strategies.