FM JANUARY 2019 - digital edition

drug delivery
NEUROGLIA AS TARGETS
Non-neuronal cells can be targeted for effective drug delivery to the brain even
though reaching out to them remains a challenge
One of the major challenges in the
treatment of neuropathological
conditions is getting the drug
molecule to cross the blood-brain
barrier. The second challenge is getting
the drug to work only on the tissue/
cells that are affected. With the advent
of targeted drug delivery systems,
much attention has been given on the
subject of specifically targeting neurons.
Though targeting neurons is essential, it
is now becoming clear that therapeutic
targeting of the non-neuronal glial cells
(neuroglia) in the brain might also have
important clinical benefits. Neuroglia
encompass the non-neuronal cells in
the brain, and have been shown to
play major pathophysiological roles
in almost all neurological disorders. In
an article published in February 2017,
Madhusudanan et al. review the current
literature in “Neuroglia as targets
for drug delivery systems: A review”.
Nanomedicine. 2017 Feb;13(2):667-
679.
Why neuroglia?
Glial cells were thought to hold the
nervous system together, forming the
matrix that protects and facilitates
the functioning of neurons. The
word ‘glia’ means ‘glue’ in Greek and
thereby came the name ‘neuroglia’.
It was much later that different cell
types were identified within the neural
parenchyma. Considering their close
proximity to neurons, neuroglia are now
understood to be closely intertwined
with the functioning of neurons,
and consequently
involved in the
majority of neurological disorders.
Neuroglia include astrocytes,
oligodendrocytes, microglia, NG2-glia,
and ependymal cells in the central
nervous system, as well as Schwann
cells and satellite glial cells in the
peripheral nervous system.
Astrocytes are some of the most
studied neuroglial cells, and they
outnumber neurons 10 to 1. They are
NEUROGLIA HAVE
BEEN IMPLICATED IN
AMYOTROPHIC LATERAL
SCLEROSIS, ALZHEIMER’S
DISEASE, PARKINSON’S
DISEASE, STROKE AND
CEREBROVASCULAR
DISEASE
important for neurotransmitter reuptake
and recycling, and play a critical role
in mediating neuronal homeostasis.
Astrocytes also communicate with
the blood-brain barrier, releasing
various vasoactive mediators to
regulate cerebrovascular flow. They
have been implicated in amyotrophic
lateral sclerosis, Alzheimer’s disease,
Parkinson’s disease, stroke
and cerebrovascular
disease, as well as in epilepsy,
neuropathic pain and migraine.
Microglia are resident macrophages
that form the first line of defense
in the brain. They play critical
immunomodulatory roles in the CNS,
and are responsible for clearing
damaged cells and for active
communication between neurons and
surrounding glia. Activated microglia
are implicated in Alzheimer’s disease,
Parkinson’s disease, schizophrenia as
well as in neuroinflammation.
Oligodendrocytes are specialized
cells important for neuronal myelination
and production of trophic factors
important for neuronal function.
They are implicated in multiple
sclerosis, amyotrophic lateral sclerosis,
Alzheimer’s disease and Parkinson’s
disease. NG-2 cells, precursor cells for
oligodendrocytes, also share a close
relationship with neurons. They carry
Na+, K+ and Ca+ channels, in addition
to GABA and glutamate receptors.
However, they have not yet been fully
characterized and only a few studies
have been carried out for targeting
them.
In the peripheral nervous
system, the Schwann
Liposome
polymeric
nanoparticles
68 / FUTURE MEDICINE / JANUARY 2019