Biomedical Engineering Reference
In-Depth Information
biocompatibility, target-specific affinity, escape from the RES, stability in
blood, and ability to perform in the controlled drug release must be considered
during the development of the nanocarriers. Excellent candidates as nanocarri-
ers must have the following properties
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:
Size: <100 nm diameter
l
Nontoxic, biodegradable, and biocompatible
l
No particle aggregation in blood
l
No opsonization by proteins
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BBB-targeted chemistry: use of cell surface, ligands, and receptor-mediated
endocytosis
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No activation of neutrophils and noninflammatory
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No platelet aggregation
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Escapes the RES
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Prolonged circulation time
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Cost-effective scaled-up manufacturing/production
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Ease of complexation with drugs that may be in the form of small molecules,
peptides, proteins, or nucleic acids
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Controlled drug release or exhibit modulation of drug release profiles.
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The engineering of NMs for drug delivery becomes more complicated when
it comes to drug delivery to the brain because of its immunologically unique
characteristics which restricts the entry of most pharmaceutical compounds. As
a result, there is a severely limited research on the applicability of nanotechnol-
ogy in CNS drug delivery that may be attributed to the lack of strategies that
can allow localized and controlled delivery of drugs across the BBB to the site
of injury or disease.
Among the few NMs that have been studied for drug delivery to the brain are
the liposomes and their related lipid NPs. Lipid NMs are the alternative to tradi-
tional colloidal carriers, such as emulsions, liposomes, and polymeric particles
that have been employed for brain tumor targeting.
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The role of apolipoprotein
A-I in the NP uptake and passage across the BBB was observed for different
types of NPs.
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For targeting, specific receptors on the brain capillaries such as
the transferrin receptor
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and the receptor for insulin
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are highly expressed by
the endothelial cells forming the BBB with the assumption that the endogenous
ligands for these receptors as well as antibodies against them can be used for
drug targeting to the CNS.
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A collection of papers on the use of NPs or drug
delivery has been included in the review by Wohlfart.
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The most popular alternative route for direct drug administration to the brain
region that is painless and safe is i.v. administration. Some approaches such as
oral route, inhalation or intratracheal instillation, i.n. drug delivery, and convec-
tion-enhanced diffusion, and intrathecal/intraventricular drug delivery systems
are other conventional modes. The administration route of NMs becomes an
important criterion of consideration to overcome the physiological barriers of
the brain. Studies have used fluorescence-labeled bovine serum albumin loaded
