Membrane-Based Nanotechnology and Drug Delivery - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 142

due to a lower value of nanoparticle inertia. This will thus require low stability
( pore lifetime) for the pore. This novel nanotechnology should be able to deal with

drug delivery targeting the cellular interior regions. Important applications of this
technology could include the treatment of various types of cell-based diseases, such
as cancer or Alzheimer's disease to name but a few. Besides, imaging of the cellular
interior regions can also be performed using this type of novel nanotechnology.
Consequently, this nanotechnology can find uses in both cell-based diagnosis and
in therapeutic applications which will enhance our understanding of various life
processes that originate inside cells.

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6.4.2 Membrane Transport of Nanoparticles Through
Non-Lipid-Lined Ion Pores

Chapters 4 and 5 showed that antimicrobial peptide alamethicin induces a 'barrel-
stave'-type ion pore/channel inside lipid membranes. This structure is a long cylinder
covering the whole bilayer thickness where the peptides align longitudinally on the
cylindrical surface. The cross-sectional area of the channel changes back-and-forth
depending on the number of participating peptides in the formation of a pore. Unlike
the pores induced by chemotherapy drugs, presented in Fig. 6.11 , the membrane
thickness near the alamethicin pore never seems to vanish completely. If nanoparticles
try to move through the alamethicin channles, they need to travel a length equivalent
to the bilayer thickness right through the cylindrical axis. This raises the possibility
for the nanoparticles to be interacting with peptides on the channels during their
relatively long journey through the hydrophobic lipid bilayer core. When traveling
through the type of pores that are induced by chemotherapy drugs, nanoparticles can
avoid the hydrophobic membrane core and can also avoid direct interactions with
pore-inducing agents. Any nanoparticles that are reluctant to interact with lipids
may be dragged through the lipid-lined toroidal pores (see Fig. 6.11 ) much easier
than those toroidal pores induced by magainin or many other peptides. Of course,
a detailed investigation can be made whether the nanoparticle transport through
ceramide channels (presented in Chaps. 4 and 5 ) appears to be an easier solution.
Despite the necessity of traveling a long distance, equivalent to the thickness of
the membrane, nanoparticles traveling through the ceramide channels meet lipids
only. This may reduce cytoxicity, but there exists a significant risk of experiencing a
much slower diffusion rate of nanoparticles into the cellular interior due to the long
length of the channel's hydrophobic core that must be traversed by the nanoparticles.
A detailed investigation aimed at finding better candidates (less toxic natural or
synthetic peptides, any biomolecules, etc.) that induce channels similar to those
induced by chemotherapy drugs may be worth undertaking in order to develop non-
toxic nanotechnology enabling the delivery of drugs into cellular interior regions.