Baclofen-loaded microspheres: preparation and efficacy testing in a new rabbit model

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Neuroscience

Background:

• Intrathecal baclofen is the standard treatment for severe spasticity.
• Current delivery methods involve expensive, uncomfortable implanted pumps with potential side effects.
• Previous research explored encapsulating baclofen in poly(lactide-co-glycolide) (PLGA) microspheres for intrathecal injection.

Purpose of the Study:

• To optimize the PLGA microsphere encapsulation process for industrial scale-up.
• To develop and validate a reliable animal model for assessing the duration of baclofen microsphere effects.
• To improve drug release profiles and reduce toxicity using alternative solvents and polymer characteristics.

Main Methods:

• Modified the encapsulation process using ethyl acetate instead of methylene chloride and high molecular weight PLGA polymers.
• Controlled manufacturing parameters including temperature and solvent extraction rate.
• Evaluated microsphere quality, in vitro drug release over 174 days, and in vivo efficacy using electrophysiological H-reflex measurements in rabbits.

Main Results:

• Achieved high-quality microsphere batches with low variability (CV < 5%) in encapsulation efficiency and drug loading.
• Developed a formulation with sustained baclofen release over 174 days in vitro, exhibiting a 16% burst effect on day one.
• Demonstrated sustained in vivo activity of baclofen microspheres for over 35 days at a low dose, with good tolerability.

Conclusions:

• The optimized PLGA microsphere formulation provides sustained intrathecal baclofen delivery.
• This novel approach shows significant potential for improving spasticity management by enhancing efficacy and patient comfort.
• The developed animal model reliably assesses the duration of drug effect for new formulations.