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

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.

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

“…Lentivirus and adeno-associated viruses are another strategy for probing antidepressant and antipsychotic mechanisms in the brain via targeted activation or inactivation of gene expression of specific drug receptors, transporters [227][228][229] or nanocarriers (e.g., clozapine targeting 5-HT1A and D2 receptors due to its low selectivity) [241]. Considering individual characteristics of patients is also critically important for the success of psychopharmacotherapy.…”

Special Issue on “Function of Polymers in Encapsulation Process”

“…The outer layer of the carrier was grafted by polyethylene glycol (PEG). According to the author, this approach may facilitate the availability and safety of the drug, enhance the selectivity of its performance, and subsequently increase the efficiency of schizophrenia therapy [ 7 ].…”