Hybrid Nanoparticles for Haloperidol Encapsulation: Quid Est Optimum?

Abstract

The choice of drug delivery carrier is of paramount importance for the fate of a drug in a human body. In this study, we have prepared the hybrid nanoparticles composed of FDA-approved Eudragit L100-55 copolymer and polymeric surfactant Brij98 to load haloperidol—an antipsychotic hydrophobic drug used to treat schizophrenia and many other disorders. This platform shows good drug-loading efficiency and stability in comparison to the widely applied platforms of mesoporous silica (MSN) and a metal–organic framework (MOF). ZIF8, a biocompatible MOF, failed to encapsulate haloperidol, whereas MSN only showed limited encapsulation ability. Isothermal titration calorimetry showed that haloperidol has low binding with the surface of ZIF8 and MSN in comparison to Eudragit L100-55/Brij98, thus elucidating the striking difference in haloperidol loading. With further optimization, the haloperidol loading efficiency could reach up to 40% in the hybrid Eudragit L100-55/Brij98 nanoparticles with high stability over several months. Differential scanning calorimetry studies indicate that the encapsulated haloperidol stays in an amorphous state inside the Eudragit L100-55/Brij98 nanoparticles. Using a catalepsy and open field animal tests, we proved the prolongation of haloperidol release in vivo, resulting in later onset of action compared to the free drug.

Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System

“…In another interesting report, it was illustrated that hybrid nanoparticles made up of Brij98 (surfactant) and Eudragit L100-55 were able to efficiently deliver the antipsychotic drug, haloperidol. The prepared nanoparticles showed good stability and drug loading efficiency ( Filippov et al, 2021 ).…”

Cataleptogenic Effect of Haloperidol Formulated in Water-Soluble Calixarene-Based Nanoparticles

“…In addition, the loading of haloperidol into nanoparticles based on anionic PEGylated Eudragit ® L100-55 and cationic Eudragit ® EPO polymers significantly increased the in vivo nose-to-brain delivery of haloperidol [ 22 ]. However, when haloperidol was loaded into hybrid nanoparticles based on the Eudragit L100-55 copolymer and the polymeric surfactant Brij98, its absorption was slowed down, which was expressed by a decrease in the pharmacological activity (cataleptogenic effect) compared to its free form [ 23 ]. Attempts to develop intranasal formulations are caused by problems with the oral delivery of haloperidol, when the drug enters systemic circulation after undergoing first-pass metabolism.…”