title: Encapsulation of clozapine in polymeric nanocapsules and its biological effects.
abstract: Clozapine is an effective atypical antipsychotic drug that unfortunately exhibits poor oral bioavailability. Moreover, the clinical use of the compound is limited because of its numerous unfavorable and unsafe side effects. Therefore, the aim of the present study was the development of a new nanocarrier for a more effective clozapine delivery. Here, clozapine was encapsulated into polymeric nanocapsules (NCs). Polyelectrolyte multilayer shells were constructed by the technique of sequential adsorption of polyelectrolytes (LbL) using biocompatible polyanion PGA (Poly-L-glutamic acid, sodium salt) and polycation PLL (poly-L-lysine) on clozapine-loaded nanoemulsion cores. Pegylated external layers were prepared using PGA-g-PEG (PGA grafted by PEG (polyethylene glycol)). Clozapine was successfully loaded into the PLL-PGA nanocarriers (CLO-NCs) with an average size of 100 nm. In vitro analysis of the interactions of the CLO-NCs with the cells of the mononuclear phagocytic system (MPS) was conducted. Cell biocompatibility, phagocytosis potential, and cellular uptake were studied. Additionally, the biodistribution and behavioral effects of the encapsulated clozapine were also studied. The results indicate that surface modified (by PEG grafting) polymeric PLL-PGA CLO-NCs are very promising nanovehicles for improving clozapine delivery.
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-348 Krakow, Poland. Electronic address: sylwia.lukasiewicz@uj.edu.pl.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Łukasiewicz
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry PAS, 30-239 Krakow, Poland. Electronic address: ncszczep@cyf-kr.edu.pl.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Szczepanowicz
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry PAS, 30-239 Krakow, Poland. Electronic address: ncpodgor@cyf-kr.edu.pl.
authors.forename: Karolina
authors.initials: K
authors.lastname: Podgórna
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-348 Krakow, Poland. Electronic address: ewa.blasiak@uj.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Błasiak
authors.affiliation: Department of Neuroscience, Karolinska Institutet, 171-77 Stockholm, Sweden. Electronic address: nathermmm@hotmail.com.
authors.forename: Nather
authors.initials: N
authors.lastname: Majeed
authors.affiliation: Department of Neuroscience, Karolinska Institutet, 171-77 Stockholm, Sweden. Electronic address: Sven.Ove.Ogren@ki.se.
authors.forename: Sven Ove Ögren
authors.initials: SOÖ
authors.lastname: Ogren
authors.affiliation: Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-348 Krakow, Poland. Electronic address: witold.nowak@uj.edu.pl.
authors.forename: Witold
authors.initials: W
authors.lastname: Nowak
authors.affiliation: Jerzy Haber Institute of Catalysis and Surface Chemistry PAS, 30-239 Krakow, Poland. Electronic address: ncwarszy@cyf-kr.edu.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Warszyński
authors.affiliation: Department of Physical Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-348 Krakow, Poland. Electronic address: marta.dziedzicka-wasylewska@uj.edu.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Dziedzicka-Wasylewska
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003024:Clozapine / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004339:Drug Compounding; D005434:Flow Cytometry; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009043:Motor Activity / Q000187:drug effects; D053769:Nanocapsules / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D014150:Antipsychotic Agents; D053769:Nanocapsules; D011107:Polylysine; D011099:Polyglutamic Acid; D003024:Clozapine
keywords: Clozapine; Encapsulation; Macrophage; Nanocapsule; Schizophrenia