Abstract
Clozapine, the second generation antipsychotic drug, is one of the prominent compounds used for treatment of schizophrenia. Unfortunately, use of this drug is still limited due to serious side effects connected to its unspecific and non-selective action. Nevertheless, clozapine still remains the first-choice drug for the situation of drug-resistance schizophrenia. Development of the new strategy of clozapine delivery into well-defined parts of the brain has been a great challenge for modern science. In the present paper we focus on the presentation of a new nanocarrier for clozapine and its use for targeted transport, enabling its interaction with the dopamine D2 and serotonin 5-HT1A heteromers (D2-5-HT1A) in the brain tissue. Clozapine polymeric nanocapsules (CLO-NCs) were prepared using anionic surfactant AOT (sodium docusate) as an emulsifier, and bio-compatible polyelectrolytes such as: poly-l-glutamic acid (PGA) and poly-l-lysine (PLL). Outer layer of the carrier was grafted by polyethylene glycol (PEG). Several variants of nanocarriers containing the antipsychotic varying in physicochemical parameters were tested. This kind of approach may enable the availability and safety of the drug, improve the selectivity of its action, and finally increase effectiveness of schizophrenia therapy. Moreover, the purpose of the manuscript is to cover a wide scope of the issues, which should be considered while designing a novel means for drug delivery. It is important to determine the interactions of a new nanocarrier with many cell components on various cellular levels in order to be sure that the new nanocarrier will be safe and won’t cause undesired effects for a patient.
Highlights
The use of nanotechnology in molecular pharmacology has been attracting more and more attention
It is important to determine the interactions of a new nanocarrier with many cell components on various cellular levels in order to be sure that the new nanocarrier will be safe and won’t cause undesired effects for a patient
The most promising results were obtained for six-layer capsules with a pegylated outer layer (CLO-NCs VI-poly-L-glutamic acid (PGA)-g(39)-polyethylene glycol (PEG)), where the cell viability was almost 100%, after 24 and 48 h incubation with NCs
Summary
The use of nanotechnology in molecular pharmacology has been attracting more and more attention. Finding effective nanocarriers dedicated to the controlled delivery of active compounds requires systematic studies leading to the optimization of their interaction with target cells. This interaction depends on the type and physicochemical properties of the carrier and, above all, on the modification of its external layer. The interaction between the NCs and the cell membrane is the main factor influencing this process and depends on the shape, size, flexibility, surface charge, modification and functionalization of a capsule [26,27,28,29]. Pegylation spatially stabilized the NCs and prevented their aggregation [23,24]
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