Neurodegenerative disorder treatment is a challenge mainly due to the difficulty of drug transport across the blood-brain barrier [1]. Intranasal administration of nanoparticles as carrier system may increase drug concentration into the brain [2]. Geraniol (GER) has demonstrated antioxidant and neuroprotective activities in Parkinson’s disease animal models [3]. However, due to its volatility, GER is hardly incorporated into freezedrying nanoparticles. On the other hand, GER-ursodeoxycholic acid conjugate (GER-UDCA) is a non-volatile derivative with high potentiality to be incorporated into nanocarriers. Therefore, in this work GER-UDCA-loaded Solid Lipid Nanoparticles (SLNs) and PLGA nanoparticles (NPs) intended for nose-to-brain delivery were developed and characterized. SLNs were prepared by emulsion/solvent evaporation method and NPs by nanoprecipitation method. Briefly, formulations were optimized considering various processing variables and nanoparticle characterization was performed in terms of morphology, size, surface charge, drug loading (DL%), encapsulation efficiency (EE%) and in vitro drug release. Finally, the stability of free and encapsulated GERUDCA was evaluated in enzymatic medium from rat liver homogenates. GER-UDCA-SLN and GER-UDCA-NPs showed spherical shape, mean size of 120/180 nm with polydispersity index < 0.2, and zeta potential around −22/-26 mV, respectively. After freeze-drying, the DL% was 6% for SLN and 12% for NPs with EE% values of 89.3% and 60.1%, respectively. Preliminary data regarding in vitro release of GER-UDCA from the nanoparticles evidenced a higher dissolution rate than the free drug, probably due to the increase of surface contact. Results in liver rat homogenate suggested a contribution of the nanoparticles in the stability of the prodrug in physiologic environments. In conclusion, these GER-UDCA-loaded nanocarriers demonstrated a possible application in further in vivo studies of nose-to-brain drug delivery.
Polymeric and Solid Lipid Nanoparticles for nose-to-brain delivery of geraniolursodeoxycholic acid conjugate: development and characterization studies / Edilson Oliveira Junior, ; Truzzi, Eleonora; Maretti, Eleonora; Leo, Eliana Grazia; Dalpiaz, Alessandro; Rustichelli, Cecilia; Marco, Fogagnolo; Eliana, Lima. - (2018), pp. 83-83. (Intervento presentato al convegno INTERNATIONAL CONFERENCE ON NANOMEDICINE tenutosi a ROMA nel 18-20 GIUGNO).
Polymeric and Solid Lipid Nanoparticles for nose-to-brain delivery of geraniolursodeoxycholic acid conjugate: development and characterization studies
Truzzi Eleonora;Eleonora Maretti;Eliana Leo;Alessandro Dalpiaz;Cecilia Rustichelli;
2018
Abstract
Neurodegenerative disorder treatment is a challenge mainly due to the difficulty of drug transport across the blood-brain barrier [1]. Intranasal administration of nanoparticles as carrier system may increase drug concentration into the brain [2]. Geraniol (GER) has demonstrated antioxidant and neuroprotective activities in Parkinson’s disease animal models [3]. However, due to its volatility, GER is hardly incorporated into freezedrying nanoparticles. On the other hand, GER-ursodeoxycholic acid conjugate (GER-UDCA) is a non-volatile derivative with high potentiality to be incorporated into nanocarriers. Therefore, in this work GER-UDCA-loaded Solid Lipid Nanoparticles (SLNs) and PLGA nanoparticles (NPs) intended for nose-to-brain delivery were developed and characterized. SLNs were prepared by emulsion/solvent evaporation method and NPs by nanoprecipitation method. Briefly, formulations were optimized considering various processing variables and nanoparticle characterization was performed in terms of morphology, size, surface charge, drug loading (DL%), encapsulation efficiency (EE%) and in vitro drug release. Finally, the stability of free and encapsulated GERUDCA was evaluated in enzymatic medium from rat liver homogenates. GER-UDCA-SLN and GER-UDCA-NPs showed spherical shape, mean size of 120/180 nm with polydispersity index < 0.2, and zeta potential around −22/-26 mV, respectively. After freeze-drying, the DL% was 6% for SLN and 12% for NPs with EE% values of 89.3% and 60.1%, respectively. Preliminary data regarding in vitro release of GER-UDCA from the nanoparticles evidenced a higher dissolution rate than the free drug, probably due to the increase of surface contact. Results in liver rat homogenate suggested a contribution of the nanoparticles in the stability of the prodrug in physiologic environments. In conclusion, these GER-UDCA-loaded nanocarriers demonstrated a possible application in further in vivo studies of nose-to-brain drug delivery.
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