Rapamycin Loaded Solid Lipid Nanoparticles as a New Tool to Deliver mTOR Inhibitors: Formulation and in Vitro Characterization.
Recently, the use of mammalian target of rapamycin (mTOR) inhibitors, in particular rapamycin (Rp), has been suggested to improve the treatment of neurodegenerative diseases. However, as Rp is a strong immunosuppressant, specific delivery to the brain has been postulated to avoid systemic exposure. In this work, we fabricated new Rp loaded solid lipid nanoparticles (Rp-SLN) stabilized with polysorbate 80 (PS80), comparing two different methods and lipids. The formulations were characterized by differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), wide angle X-ray scattering (WAXS), cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS) and particle tracking.In vitrorelease and short-term stability were assessed. Biological behavior of Rp-SLN was tested in SH-SY5Y neuroblastoma cells. The inhibition of mTOR complex 1 (mTORC1) was evaluated over time by a pulse-chase study compared to free Rp and Rp nanocrystals. Compritol Rp-SLN resulted more stable and possessing proper size and surface properties with respect to cetyl palmitate Rp-SLN. Rapamycin was entrapped in an amorphous form in the solid lipid matrix that showed partial crystallinity with stable Lβ, sub-Lα and Lβ' arrangements. PS80 was stably anchored on particle surface. No drug release was observed over 24 h and Rp-SLN had a higher cell uptake and a more sustained effect over a week. The mTORC1 inhibition was higher with Rp-SLN. Overall, compritol Rp-SLN show suitable characteristics and stability to be considered for further investigation as Rp brain delivery system.
Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06126 Perugia, Italy. alicepolchi@virgilio.it.
Alice
A
Polchi
Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06126 Perugia, Italy. alessandro.magini@unipg.it.
Alessandro
A
Magini
NanoBioMedical Centre, Faculty of Physics, Adam Mickiewicz University in Poznań, 61614 Poznań, Poland. jmaz@amu.edu.pl.|Molecular Biophysics Division, Faculty of Physics, Adam Mickiewicz University in Poznań, 61614 Poznań, Poland. jmaz@amu.edu.pl.
Jarosław
J
Mazuryk
Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06126 Perugia, Italy. brunella.tancini@unipg.it.
Brunella
B
Tancini
NanoBioMedical Centre, Faculty of Physics, Adam Mickiewicz University in Poznań, 61614 Poznań, Poland. gapinski@amu.edu.pl.|Molecular Biophysics Division, Faculty of Physics, Adam Mickiewicz University in Poznań, 61614 Poznań, Poland. gapinski@amu.edu.pl.
Jacek
J
Gapiński
NanoBioMedical Centre, Faculty of Physics, Adam Mickiewicz University in Poznań, 61614 Poznań, Poland. patkowsk@amu.edu.pl.|Molecular Biophysics Division, Faculty of Physics, Adam Mickiewicz University in Poznań, 61614 Poznań, Poland. patkowsk@amu.edu.pl.
Adam
A
Patkowski
Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy. stefano.giovagnoli@unipg.it.
Stefano
S
Giovagnoli
Department of Chemistry, Biology and Biotechnology, University of Perugia, Via del Giochetto, 06126 Perugia, Italy. carla.emiliani@unipg.it.
Carla
C
Emiliani
SH-SY5Y neuroblastoma cells; drug delivery; formulation; rapamycin; solid lipid nanoparticles