Chemistry Reference
In-Depth Information
The formulations of solid lipid nanoparticles have generally been used for the
administration of peptides by the oral route. The advantages of emulsifi ed
microemulsions (EMEs) (Yaghmur and Glatter, 2009) for peptide delivery
remain to be explored.
11.2.3
Human Cellular Model for Expression of Brain Receptors
Cell cultures are considered as a good model to study the activity of therapeu-
tic molecules prior to preclinical trials. A human cell line expressing the tyro-
sine kinase receptor TrkB was selected as a model for in vitro screening of the
ligand binding to brain receptors. The SH-SY5Y cell line has been previously
employed in studies of neuroprotectants, antidepressants, and anti-Parkinson's,
as well as for the expression of the amyloid precursor protein, which is the
main constituent of the plaques associated with Alzheimer's disorders (Donnici
et al., 2008; Presgraves et al., 2004; Ruiz-Leon and Pascual, 2003).
Despite the fact that they are not identical to mature neurons in the human
brain, the differentiated SH-SY5Y cells are quite suitable to study the interac-
tions of therapeutic formulations with neurotrophic pathways (see Fig. 11.15).
Their advantage over primary cell cultures is that they provide an almost
infi nite amount of human cells with the same biochemical characteristics and
do not require the use of antimitotics as with other cellular models. Owing to
their dependence on trophic BDNF after treatment, the SH-SY5Y cells, pre-
senting TrkB receptor populations, permit to study the mechanisms of neuro-
protection (Kaplan et al., 1993; Serres and Carney, 2006). Therefore, this
model system appears valuable for exploring the therapeutic potential of
neuroprotectants in neurodegenerative disorders. A protocol to quantify neu-
ritogenesis and perform automated image capture with these cells has been
set up by the method of fl uorescent immunocytochemistry (Simpson et al.,
2001). It may allow screening of small-molecule mimetics of neurotrophic
growth factors.
For SH-SY5Y cells, a protocol of differentiation, based on a sequential
treatment with retinoic acid and BDNF, has been proposed (Cernianu et al.,
2008; Encinas et al., 2000; Nishida et al., 2008). It yields a homogeneous popu-
lation of differentiated neuronal cells expressing the TrkB receptor with syn-
chronized cell cycles. The treated neuroblastoma cells are strictly dependent
on BDNF for survival. When the short- and long-term treatment with BDNF
is interrupted, the cells enter in a process of programmed cell death with
apoptosis patterns. This treatment allows the growth of neurites, forming
extensive networks. The stability of the cell culture is ensured for at least 3
weeks in the presence of BDNF (Encinas et al., 2000). Cernianu et al. (2008)
have reported latent cells after treatment with retinoic acid, which has caused
an arrest of the cell proliferation and maintenance of the viability even
after 10 days of remedy. In addition, the treatment with an omega-3 polyun-
saturated fatty acid (EPA) for 3 days was found to increase the cellular viabi-
lity and the expression of neurotrophin (TrkB) receptors on the SH-SY5Y
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