Sustained release of naltrexone from glyceride implants

Area of Science:

• Pharmacology
• Biomaterials Science
• Drug Delivery Systems

Background:

• Naltrexone is a narcotic antagonist used to manage opioid and alcohol dependence.
• Developing long-acting injectable formulations for sustained drug release is crucial for therapeutic efficacy.
• Natural glycerides offer potential as biodegradable matrices for drug delivery implants.

Purpose of the Study:

• To develop and characterize injectable naltrexone implants using solid dispersions in natural glycerides.
• To evaluate the in vivo release kinetics and efficacy of these implants in blocking narcotic effects.
• To assess the biocompatibility and degradation profile of the naltrexone implants.

Main Methods:

• Formation of naltrexone solid dispersions in natural glycerides as pellets or microparticles.
• In vivo administration to mice and assessment of naltrexone release rates.
• Evaluation of blockade against morphine's anti-nociceptive effects.
• Histopathological examination for tissue compatibility in multiple animal species.

Main Results:

• Both implant forms (pellets and microparticles) achieved sustained naltrexone release in vivo.
• Naltrexone delivery effectively blocked morphine's anti-nociceptive action for at least one month.
• Release rates were tunable by adjusting naltrexone concentration and glyceride composition.
• Implants demonstrated good biocompatibility across mice, rats, rabbits, monkeys, and swine.

Conclusions:

• Injectable naltrexone implants based on natural glyceride solid dispersions are effective for long-term narcotic antagonist delivery.
• The formulation allows for controlled drug release and demonstrates a favorable safety profile.
• These implants represent a promising strategy for managing addiction and substance abuse disorders.