Biomedical Engineering Reference
In-Depth Information
Chagas's diseases and toxoplasmosis, two diseases with intracytoplasmic targets
within non phagocytic cells in tissues where inflammation is almost absent remain
as unsurpassed challenges for nanomedical approaches.
Keywords Chlamydiasis • Intracellular drug delivery • Intracellular bacteria
• Intracellular protozoa
1
Nanomedicines in Drug Delivery Against Intracellular
Bacteria and Protozoa
The branch of Nanotechnology that employs nano-objects (namely metal and oxides
nanoparticles, polymeric and lipid nanoparticles, dendrimers, micelles, liposomes and
other vesicles under 200-300 nm, that will be referred in general as “nanoparticles”)
( ISO 2008 ), such as therapeutic drug carriers diagnosis agents, nanodevices and nano-
scaffolds for tissue engineering in the medical field, is known as Nanomedicine
(European Science Foundation 2005 ). A drug loaded into a nano-object is regarded as
a “nanomedicine”. In this way, drug's pharmacokinetics and pharmacodynamics
become independent from it's chemical structure, to depend on the structure of the
nano-object. On the other hand, eucariotic cells recognize and capturate nano-objects.
If properly designed, nano-objects can cross anatomical and phenomenological barriers
such as the gastrointestinal mucus, the skin and the blood brain barrier (Alonso 2004 ).
Therefore, carried drugs can be targeted delivered to cells in spite of their poor bioavail-
ability, lability in circulation, poor cell penetration and/or non selective distribution in
their free form (Tan et al. 2010 ). From the advent of peguilated liposomes, such attrac-
tive goals are responsible for the exponential increase in the number of articles dealing
with preclinical applications of nanomedicine that initiated circa 25 years ago (Rannard
and Owen 2009 ). Preclinical research has also fostered the entering of nanomedicines
in new clinical trials (Emerich and Thanos 2006 ; Sakamoto et al. 2010 ).
In order to succeed, a delivery strategy mediated by nanomedicines neccesitates
of a suitable anatomo-pathological environment or a target site having an adequate
tissue/cell activity. A clear example are the oncologic therapies, where the EPR
(enhanced permeation and retention) effect enables the circulating nanoparticles to
extravasate and accumulate in the neighborhood of target cells (passive targeting),
diminishing the toxicity of treatments to solid tumors (Stern et al. 2010 ). Passive
targeting mediated by EPR effect, plus a structural design that allows its cellular
uptake by caveolin mediated endocytosis, is responsible for the improved therapeu-
tic efficacy of products such as Abraxane (paclitaxel in albumin nanoparticles)
(Petrelli et al. 2010 ). In vaccinology on the other hand, the phagocytic activity of
antigen presenting cells is used to favour the uptake, processing and presentation of
antigens loaded in nanoparticles. In pre-clinics, different types of nanoparticles are
used as human and veterinary vaccine adjuvants (Peek et al. 2008 ).
Nanomedical pharmacotherapy is classically administered by intravenous (i.v.)
route. To avoid opsonization and aggregation while in circulation, the surface of
intravenously injected nanoparticles is pegylated (a coverage made of a ~50 Å thick
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