Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation
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2015
Authors
Dordevic, Sanela MCekic, Nebojsa

Savić, Miroslav M.

Isailovic, Tanja M
Randjelović, Danijela

Marković, Bojan D.

Savić, Saša R.
Stamenic, Tamara Timic

Daniels, Rolf

Savić, Snežana D.

Article (Published version)

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This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution LT 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogen...ization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.
Keywords:
Parenteral nanoemulsions / Brain targeting / Poorly water-soluble drugs / General factorial design / Physical stability / PharmacokineticsSource:
International Journal of Pharmaceutics, 2015, 493, 1-2, 40-54Publisher:
- Elsevier
Funding / projects:
- Development of micro- and nanosystems as carriers for drugs with anti-inflammatory effect and methods for their characterization (RS-34031)
- Behavioral ?ffects following repeated administration of newly synthesized ligands selective for distinct subtypes of GABAA receptor benzodiazepine binding site: comparison with standard psychopharmacologic drugs (RS-175076)
- Micro- Nanosystems and Sensors for Electric Power and Process Industry and Environmental Protection (RS-32008)
Note:
- Accepted version: http://cer.ihtm.bg.ac.rs/handle/123456789/3201
DOI: 10.1016/j.ijpharm.2015.07.007
ISSN: 0378-5173
PubMed: 26209070
WoS: 000360492000005
Scopus: 2-s2.0-84938080952
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Institution/Community
IHTMTY - JOUR AU - Dordevic, Sanela M AU - Cekic, Nebojsa AU - Savić, Miroslav M. AU - Isailovic, Tanja M AU - Randjelović, Danijela AU - Marković, Bojan D. AU - Savić, Saša R. AU - Stamenic, Tamara Timic AU - Daniels, Rolf AU - Savić, Snežana D. PY - 2015 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1697 AB - This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution LT 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting. PB - Elsevier T2 - International Journal of Pharmaceutics T1 - Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation VL - 493 IS - 1-2 SP - 40 EP - 54 DO - 10.1016/j.ijpharm.2015.07.007 ER -
@article{ author = "Dordevic, Sanela M and Cekic, Nebojsa and Savić, Miroslav M. and Isailovic, Tanja M and Randjelović, Danijela and Marković, Bojan D. and Savić, Saša R. and Stamenic, Tamara Timic and Daniels, Rolf and Savić, Snežana D.", year = "2015", abstract = "This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution LT 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.", publisher = "Elsevier", journal = "International Journal of Pharmaceutics", title = "Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation", volume = "493", number = "1-2", pages = "40-54", doi = "10.1016/j.ijpharm.2015.07.007" }
Dordevic, S. M., Cekic, N., Savić, M. M., Isailovic, T. M., Randjelović, D., Marković, B. D., Savić, S. R., Stamenic, T. T., Daniels, R.,& Savić, S. D.. (2015). Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation. in International Journal of Pharmaceutics Elsevier., 493(1-2), 40-54. https://doi.org/10.1016/j.ijpharm.2015.07.007
Dordevic SM, Cekic N, Savić MM, Isailovic TM, Randjelović D, Marković BD, Savić SR, Stamenic TT, Daniels R, Savić SD. Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation. in International Journal of Pharmaceutics. 2015;493(1-2):40-54. doi:10.1016/j.ijpharm.2015.07.007 .
Dordevic, Sanela M, Cekic, Nebojsa, Savić, Miroslav M., Isailovic, Tanja M, Randjelović, Danijela, Marković, Bojan D., Savić, Saša R., Stamenic, Tamara Timic, Daniels, Rolf, Savić, Snežana D., "Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation" in International Journal of Pharmaceutics, 493, no. 1-2 (2015):40-54, https://doi.org/10.1016/j.ijpharm.2015.07.007 . .