Encapsulation of clozapine into polycaprolactone nanoparticles as a promising strategy of the novel nanoformulation of the active compound

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 proinflammatory 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.

Physico-chemical Characterization and Biosafety Evaluation of Atorvastatin Nanocapsules Co-encapsulated with Ginger Oil or Grape Seed Oil

“…In this study, the pH results for NCAtG and NCAtU were 5.79 ± 0.4 and 5.60 ± 0.3, respectively. These values indicating formulations with an acid character are usual in other studies that used PCL as a coating polymer [36,37]. In addition, both ginger oil and grape seed oil have phenolic compounds in their compositions and hydroxyls that can be ionized in their chemical structures [38].…”

Brain targeting efficiency of intranasal clozapine-loaded mixed micelles following radio labeling with Technetium-99m

“…CLZ was effectively loaded into proniosomal gel and achieved transdermal drug delivery with high entrapment efficiency and good permeation manner (Tareen et al, 2020 ). The encapsulation of CLZ into polycaprolactone (Łukasiewicz et al, 2019 ) resulted in promising nanovehicles of antipsychotic drugs.…”

Development of a New Polymeric Nanocarrier Dedicated to Controlled Clozapine Delivery at the Dopamine D2-Serotonin 5-HT1A Heteromers

“…Moreover, the factors affecting drug encapsulation efficiency, particle size, surface charge, and surface hydrophilicity have been studied [17]. Additionally one can find some research that provides a brief summary and discussion of the progress and development in the delivery of other antipsychotics (e.g., aripiprazol, olanzapine, paliperidone) with nanoparticle formulations [18][19][20][21][22].…”