Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances
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2017
Authors
Đorđević, SanelaSantrač, Anja
Cekić, Nebojša
Marković, Bojan
Divović, Branka
Ilić, Tanja
Savić, Miroslav
Savić, Snežana
Article (Published version)
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This work aimed to deepen the lately acquired knowledge about parenteral nanoemulsions as carriers for brain delivery of risperidone, a poorly water-soluble antipsychotic drug, through establishing the prospective relationship between their physicochemical, pharmacokinetic, biodistribution, and behavioral performances. For this purpose, two optimized risperidone-loaded nanoemulsions, stabilized by lecithin or lecithin/polysorbate 80 mixture, and costabilized by sodium oleate, were produced by high-pressure homogenization. The characterization revealed the favorable droplet size, narrow size distribution, high surface charge, with proven stability to autoclaving and long-term stability for at least one year at 25 +/- 2 degrees C. Pharmacokinetic and tissue distribution results demonstrated improved plasma, liver, and brain pharmacokinetic parameters, resulting in 1.2-1.5-fold increased relative bioavailability, 1.1-1.8-fold decreased liver distribution, and about 1.3-fold improved brain... uptake of risperidone active moiety following intraperitoneal administration of nanoemulsions relative to solution in rats. In behavioral study, investigated nanoemulsions showed pronounced reduction in basal and, more pertinently, amphetamine-induced locomotor activity in rats, with an early onset of antipsychotic action, and this effect lasted at least 90 min after drug injection. Together, these findings corroborate the applicability of parenteral nanoemulsions as carriers for enhanced brain delivery of risperidone, further suggesting their promise in acute psychosis treatment or other emergency situations.
Keywords:
Parenteral nanoemulsion / Poorly water-soluble drug / Long-term stability / Pharmacokinetics / Tissue distribution / Antipsychotic efficiencySource:
International Journal of Pharmaceutics, 2017, 533, 2, 421-430Publisher:
- Elsevier Science BV, Amsterdam
Funding / projects:
- Development of micro- and nanosystems as carriers for drugs with anti-inflammatory effect and methods for their characterization (RS-MESTD-Technological Development (TD or TR)-34031)
DOI: 10.1016/j.ijpharm.2017.05.051
ISSN: 0378-5173
PubMed: 28552767
WoS: 000414188500013
Scopus: 2-s2.0-85020132880
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Institution/Community
PharmacyTY - JOUR AU - Đorđević, Sanela AU - Santrač, Anja AU - Cekić, Nebojša AU - Marković, Bojan AU - Divović, Branka AU - Ilić, Tanja AU - Savić, Miroslav AU - Savić, Snežana PY - 2017 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2883 AB - This work aimed to deepen the lately acquired knowledge about parenteral nanoemulsions as carriers for brain delivery of risperidone, a poorly water-soluble antipsychotic drug, through establishing the prospective relationship between their physicochemical, pharmacokinetic, biodistribution, and behavioral performances. For this purpose, two optimized risperidone-loaded nanoemulsions, stabilized by lecithin or lecithin/polysorbate 80 mixture, and costabilized by sodium oleate, were produced by high-pressure homogenization. The characterization revealed the favorable droplet size, narrow size distribution, high surface charge, with proven stability to autoclaving and long-term stability for at least one year at 25 +/- 2 degrees C. Pharmacokinetic and tissue distribution results demonstrated improved plasma, liver, and brain pharmacokinetic parameters, resulting in 1.2-1.5-fold increased relative bioavailability, 1.1-1.8-fold decreased liver distribution, and about 1.3-fold improved brain uptake of risperidone active moiety following intraperitoneal administration of nanoemulsions relative to solution in rats. In behavioral study, investigated nanoemulsions showed pronounced reduction in basal and, more pertinently, amphetamine-induced locomotor activity in rats, with an early onset of antipsychotic action, and this effect lasted at least 90 min after drug injection. Together, these findings corroborate the applicability of parenteral nanoemulsions as carriers for enhanced brain delivery of risperidone, further suggesting their promise in acute psychosis treatment or other emergency situations. PB - Elsevier Science BV, Amsterdam T2 - International Journal of Pharmaceutics T1 - Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances VL - 533 IS - 2 SP - 421 EP - 430 DO - 10.1016/j.ijpharm.2017.05.051 ER -
@article{ author = "Đorđević, Sanela and Santrač, Anja and Cekić, Nebojša and Marković, Bojan and Divović, Branka and Ilić, Tanja and Savić, Miroslav and Savić, Snežana", year = "2017", abstract = "This work aimed to deepen the lately acquired knowledge about parenteral nanoemulsions as carriers for brain delivery of risperidone, a poorly water-soluble antipsychotic drug, through establishing the prospective relationship between their physicochemical, pharmacokinetic, biodistribution, and behavioral performances. For this purpose, two optimized risperidone-loaded nanoemulsions, stabilized by lecithin or lecithin/polysorbate 80 mixture, and costabilized by sodium oleate, were produced by high-pressure homogenization. The characterization revealed the favorable droplet size, narrow size distribution, high surface charge, with proven stability to autoclaving and long-term stability for at least one year at 25 +/- 2 degrees C. Pharmacokinetic and tissue distribution results demonstrated improved plasma, liver, and brain pharmacokinetic parameters, resulting in 1.2-1.5-fold increased relative bioavailability, 1.1-1.8-fold decreased liver distribution, and about 1.3-fold improved brain uptake of risperidone active moiety following intraperitoneal administration of nanoemulsions relative to solution in rats. In behavioral study, investigated nanoemulsions showed pronounced reduction in basal and, more pertinently, amphetamine-induced locomotor activity in rats, with an early onset of antipsychotic action, and this effect lasted at least 90 min after drug injection. Together, these findings corroborate the applicability of parenteral nanoemulsions as carriers for enhanced brain delivery of risperidone, further suggesting their promise in acute psychosis treatment or other emergency situations.", publisher = "Elsevier Science BV, Amsterdam", journal = "International Journal of Pharmaceutics", title = "Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances", volume = "533", number = "2", pages = "421-430", doi = "10.1016/j.ijpharm.2017.05.051" }
Đorđević, S., Santrač, A., Cekić, N., Marković, B., Divović, B., Ilić, T., Savić, M.,& Savić, S.. (2017). Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances. in International Journal of Pharmaceutics Elsevier Science BV, Amsterdam., 533(2), 421-430. https://doi.org/10.1016/j.ijpharm.2017.05.051
Đorđević S, Santrač A, Cekić N, Marković B, Divović B, Ilić T, Savić M, Savić S. Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances. in International Journal of Pharmaceutics. 2017;533(2):421-430. doi:10.1016/j.ijpharm.2017.05.051 .
Đorđević, Sanela, Santrač, Anja, Cekić, Nebojša, Marković, Bojan, Divović, Branka, Ilić, Tanja, Savić, Miroslav, Savić, Snežana, "Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances" in International Journal of Pharmaceutics, 533, no. 2 (2017):421-430, https://doi.org/10.1016/j.ijpharm.2017.05.051 . .