Chemistry Reference
In-Depth Information
11.1
Introduction
320
11.2
Peptide Targeting and Delivery
321
11.2.1
Choice of Therapeutic Peptide with Neurotrophic Properties
321
11.2.2
Current Problems in Peptide Delivery with Lipid
Nanocarriers—Nanosystems Obtained from Polar Lipids
Hydrated in Aqueous Medium
323
11.2.3
Human Cellular Model for Expression of Brain Receptors
331
11.3
Experimental Section
332
11.3.1
Preparation of Lipid Nanoparticle Dispersions
332
11.3.2
Characterization of Lipid Nanocarriers
333
11.3.3
Cell Culture Assays
334
11.4
Physicochemical and Biological Investigations of Nanoparticulate
Mixed Lipid Systems
335
11.4.1
Nanoparticles Prepared from MO/DOPE - PEG
2000
/OA/EPA
Self - Assembled Lipid Mixtures
335
11.4.2
SAXS of Sterically Stabilized Nanodispersed Lipid Systems
340
11.4.3
In Vitro Assays with Human Neuroblastoma SH - SY5Y
Cell Line
341
11.5
Conclusion
347
References
349
11.1
INTRODUCTION
The development and maintenance of neuronal populations in the central
nervous system (CNS) is controlled by the binding of neurotrophic factors to
their membrane receptors in the brain (Malcangio and Lessmann, 2003; Naga-
hara et al., 2009; Nosheny et al., 2005; Pattarawarapan and Burgess, 2003; Wu
and Pardridge, 1999). The failure of the involved ligand-receptor interactions
is often associated to a defi ciency of neurotrophin molecules and is responsible
for several neurodegenerative diseases and certain psychiatric disorders
(Desmet and Peeper, 2006; Fumagalli et al., 2006; Pillai and Mahadik, 2008;
Sun and Wu, 2006). The therapeutic use of neurotrophins is unfortunately
restrained by their biochemical instability and rapid degradation in the bio-
logical medium. Preclinical studies have indicated the low bioavailability of
neurotrophins for the therapeutic targets (Tuszynski et al., 2005). In addition,
uncontrolled administration of brain-derived neurotrophic factor (BDNF)
might interfere with the mechanisms regulating the survival, differentiation,
and maintenance of neuronal populations.
The vectorization of the neurotrophic peptides can augment their circula-
tion times and thus improve their bioavailability by hampering the rapid
peptide elimination after delivery. We focus on liquid crystalline lipid nanopar-
ticle formulations consisting of monoolein, a PEGylated (polyethylene glycol)
lipid, and an omega-3 polyunsaturated fatty acid (eicosapentaenoic acid, EPA)
permitting to achieve nanovectors that not only can encapsulate and protect
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