Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation
Autori
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.
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
Parenteral nanoemulsions / Brain targeting / Poorly water-soluble drugs / General factorial design / Physical stability / PharmacokineticsIzvor:
International Journal of Pharmaceutics, 2015, 493, 1-2, 40-54Izdavač:
- Elsevier
Finansiranje / projekti:
- Razvoj mikro- i nanosistema kao nosača za lekove sa antiinflamatornim delovanjem i metoda za njihovu karakterizaciju (RS-34031)
- Bihejvioralni efekti ponavljane primene novosintetisanih supstanci selektivnih za pojedine podtipove benzodiazepinskog mesta vezivanja GABA A receptora: poređenje sa standardnim psihofarmakološkim lekovima (RS-175076)
- Mikro, nano-sistemi i senzori za primenu u elektroprivredi, procesnoj industriji i zaštiti životne sredine (RS-32008)
Napomena:
- This is peer-reviewed version of the artcle: S.M. Đorđević, N.D. Cekić, M.M. Savić, T.M. Isailović, D. V Ranđelović, B.D. Marković, S.R. Savić, T.T. Stamenić, R. Daniels, S.D. Savić, Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation, Int. J. Pharm. 493 (2015) 40–54. https://doi.org/10.1016/j.ijpharm.2015.07.007
- Published version: http://cer.ihtm.bg.ac.rs/handle/123456789/1697
DOI: 10.1016/j.ijpharm.2015.07.007
ISSN: 0378-5173
PubMed: 26209070
WoS: 000360492000005
Scopus: 2-s2.0-84938080952
Institucija/grupa
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/123456789/3201 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 . .