مؤتمر
Solid lipid nanoparticle as a tool to deliver mTOR inhibitors
| العنوان: | Solid lipid nanoparticle as a tool to deliver mTOR inhibitors |
|---|---|
| المؤلفون: | GIOVAGNOLI, Stefano, MAGINI, Alessandro, POLCHI, ALICE, TANCINI, Brunella, EMILIANI, Carla, Mazuryk, Jarosław, Gapinski, Jacek, Patkowski, Adam |
| المساهمون: | Giovagnoli, Stefano, Magini, Alessandro, Polchi, Alice, Mazuryk, Jarosław, Gapinski, Jacek, Tancini, Brunella, Patkowski, Adam, Emiliani, Carla |
| بيانات النشر: | Pharma+Bio Asia 2016 MYS Kuala Lumpur |
| سنة النشر: | 2016 |
| المجموعة: | IRIS Università degli Studi di Perugia |
| مصطلحات موضوعية: | mTOR inhibitors, rapamycin, solid lipid nanoparticles, brain delivery |
| الوصف: | 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, Rp loaded solid lipid nanoparticles (Rp-SLN) stabilized with polysorbate 80 (PS80) were prepared 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 vitro release 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 possessed 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 Lbeta, sub-Lalfa and Lbeta’ arrangements. PS80 was stably anchored on particle surface. The SEM and AFM imaging and shape-modeling by the combined DLS-SANS analysis revealed that Rp-SLN with a hydrodynamic radius of ∼46 nm preserve a platelet-like or flat ellipsoidal structure with a thickness of 8–9 nm. These dimensions correlate with a single lipid bilayer, organized in a triclinic Lbeta polymorph, and covered with a 1–2-nm P80 shell. Consistently, FT-IR spectra acquired in the range 52–75◦C, confirmed that the Rp incorporation within the lipid matrix decreases the point of the gel-liquid crystal (Lbeta-Lalfa) phase transition. 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 increased with Rp-SLN. Overall, compritol Rp-SLN show ... |
| نوع الوثيقة: | conference object |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| العلاقة: | ispartofbook:Development of Pharmaceutical Nanosystems; Pharma+Bio Asia 2016; http://hdl.handle.net/11391/1387984Test |
| الإتاحة: | http://hdl.handle.net/11391/1387984Test |
| رقم الانضمام: | edsbas.38EC36D9 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |