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.
Highlights
mesoporous silica nanoparticles (MSNs), metal–organic framework (MOF), and polymeric nanoparticles proved to be effective and biocompatible platforms for drug encapsulation given rise to the question: quid est optimum?—which platform works the best for haloperidol encapsulation? In order to provide an answer to this specific question, and a more general methodology to answer this question for different kinds of polymeric nanoparticles, we present a physical characterisation as a rationalisation for the behaviour of this formulation in an animal system
The MOFs and MSNs were loaded with haloperidol using the following protocol: MOF/MSM methanol solutions in the range of 1–4 mg/mL were mixed with 1 mg/mL
This preparation protocol was optimised for haloperidol loading; other solvents such as acetone, DMSO, ethanol and different mixing times were tried
Summary
Hybrid nanoparticles such as mesoporous silica and metal–organic frameworks have attracted attention in the recent years due to possibility of high drug loading in comparison with classical drug delivery carriers such as polymeric micelles [1,2], liposomes [3,4], etc. Metal–organic frameworks (MOFs) made of metal clusters and organic moieties have a variety of benefits including precise 3D structure with significant porosity and the feasibility of synthetic routes to combine metallic and organic elements in one structure [5,6,7,8] Significant progress was achieved during the last decade to exploit MOFs as a drug delivery carrier making it a prospective platform in nanomedicine [9,10,11,12] Inorganic carriers such as mesoporous silica nanoparticles (MSNs) have a porous surface which have gained MSNs the attention of drug delivery community. The quest for the best drug carrier is the main motivation of this paper having haloperidol as a model drug to have rigorous comparison of different platforms for encapsulation
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