Hybrid Nanoparticles for Haloperidol Encapsulation: Quid Est Optimum?

Area of Science:

• * Pharmaceutical Nanotechnology
• * Materials Science
• * Drug Delivery Systems

Background:

• * Effective drug delivery is crucial for therapeutic outcomes.
• * Hydrophobic drugs like haloperidol present formulation challenges.
• * Existing carriers such as mesoporous silica (MSN) and metal-organic frameworks (MOFs) have limitations in loading efficiency and stability.

Purpose of the Study:

• * To develop and characterize a novel hybrid nanoparticle system for haloperidol delivery.
• * To compare the drug-loading efficiency and stability of the new system against MSN and MOF platforms.
• * To investigate the in vivo performance of haloperidol-loaded nanoparticles.

Main Methods:

• * Preparation of hybrid nanoparticles from Eudragit L100-55 copolymer and Brij98 polymeric surfactant.
• * Drug loading efficiency and stability assessments.
• * Isothermal titration calorimetry (ITC) to study drug-carrier binding interactions.
• * Differential scanning calorimetry (DSC) to analyze the physical state of the encapsulated drug.
• * In vivo animal testing (catalepsy and open field tests) to evaluate drug release profiles.

Main Results:

• * The Eudragit L100-55/Brij98 hybrid nanoparticles demonstrated significantly higher haloperidol loading efficiency compared to ZIF8 (MOF) and MSN.
• * ZIF8 failed to encapsulate haloperidol, and MSN showed only limited encapsulation.
• * ITC studies revealed stronger binding of haloperidol to Eudragit L100-55/Brij98 compared to ZIF8 and MSN.
• * Optimized nanoparticles achieved up to 40% haloperidol loading with high stability over several months.
• * DSC confirmed haloperidol remained in an amorphous state within the nanoparticles.
• * In vivo tests showed prolonged haloperidol release, leading to a delayed onset of action compared to the free drug.

Conclusions:

• * Hybrid Eudragit L100-55/Brij98 nanoparticles represent a promising platform for the effective delivery of hydrophobic drugs like haloperidol.
• * This system overcomes the limitations of MSN and MOF carriers for haloperidol encapsulation.
• * The enhanced stability and controlled release profile of the nanoparticles offer potential for improved antipsychotic therapy.