Sustained-release ketamine-loaded nanoparticles fabricated by sequential nanoprecipitation

Area of Science:

• Nanotechnology
• Pharmacology
• Materials Science

Background:

• Ketamine is an analgesic adjuvant with a morphine-sparing effect, beneficial for cancer-related pain.
• A key limitation of ketamine is its short in vivo elimination half-life, hindering sustained therapeutic effects.
• Developing effective drug delivery systems is crucial for optimizing ketamine's clinical utility.

Purpose of the Study:

• To develop biocompatible and biodegradable ketamine-loaded nanoparticles for sustained drug release.
• To enhance the therapeutic efficacy of ketamine by overcoming its short half-life.
• To investigate novel nanoparticle formulations for improved pain management.

Main Methods:

• Preparation of ketamine-loaded poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles using a sequential nanoprecipitation method.
• Formulation of both single polymer (PEG-PLGA) and double polymer (PEG-PLGA/shellac) nanoparticles.
• In vitro and in vivo evaluation of drug release profiles and pharmacokinetic behavior.

Main Results:

• High drug loading of 41.8% achieved in ketamine-loaded PEG-PLGA nanoparticles.
• Sustained in vitro drug release observed for up to 21 days.
• In vivo studies demonstrated sustained release for over 5 days after intravenous injection in mice.

Conclusions:

• Ketamine-loaded PEG-PLGA nanoparticles demonstrate significant potential for sustained drug delivery.
• The developed nanoprecipitation method enables high drug loading and prolonged release kinetics.
• These findings support the use of ketamine nanoparticles as an advanced therapeutic option for chronic pain management.