Abstract
Clozapine (CLO), an atypical antipsychotic used in the clinic for treatment of schizophrenia, has a well-known efficacy, but its general use in clinical practice is limited because of the risk of serious side effects. Therefore, in the present work, we focused on the encapsulation of CLO into polymeric polycaprolactone nanoparticles (PCL NPs) and studies of interactions of this nanoformulation with model cells. Two types of clozapine PCL NPs (CLO-PCL NPs), pegylated and non-pegylated, were obtained by nanoemulsion templating method. The complex interactions of these NPs with three model cell lines (HEK 293, human embryonic kidney cell line; RAW 264.7, murine macrophage cell line; hCMEC/D3, model of blood-brain barrier, BBB) were studied. Cell viability, cellular uptake of NPs, NO release, expression of pro-inflammatory agents and transcytosis experiments were performed. Pegylated CLO-PCL NPs showed better results in the tests performed in the present study, in comparison to non-pegylated ones: they are not toxic to model cells; pegylated outer surface protected from their fast uptake by macrophages; they were not immunogenic; transcytosis experiments pointed to their ability to cross a model BBB. The results obtained in the present study indicate that pegylated CLO-PCL NPs are promising carrier for antipsychotic drugs directed to cross BBB. The experiments were conducted using only in vitro models but they provide valuable data in the field of nanotechnology which can be used in novel molecular pharmacology.
Highlights
Over the past decades, nanomaterials attract most attention due to the possibility of their biomedical applications
The results obtained in the present study indicate that pegylated CLO-polycaprolactone nanoparticles (PCL NPs) are promising carrier for antipsychotic drugs directed to cross blood-brain barrier (BBB)
The present study focuses on biocompatible polymeric nanoparticles made of polycaprolactone (PCL)
Summary
Nanomaterials attract most attention due to the possibility of their biomedical applications. Nanoparticles (NPs) can constitute useful tool for selective transportation of lipophilic, poorly watersoluble or even water-insoluble active compounds Such strategy allows to maintain the desired properties of the drugs by protection from the unfavourable biological environment (Anton et al 2009; Maghraby et al 2006; Mainardes and Silva 2004). Many techniques were described for modification of different surfaces to enable them to work as so-called surface capsules (Zhukova and Skorb 2017) In this way nanocarriers can be developed to achieve an “intelligent targeting” and controlled release. Over the last few years, a significant necessity emerged to evaluate PCL NPs possible pharmaceutical applications in drug delivery systems, due to their ability to transport variety of hydrophobic drugs and relatively lower cost of production and more satisfying biocompatibility (Peng et al 2015)
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