Biomedical Engineering Reference
In-Depth Information
chitosan is likely to derive from the presence of chitin in microbial
organisms that the immune system functions to keep at check.
Chitin is part of the cell wall of certain fungi and recent literature
has demonstrated that several pattern recognition molecules of the
immune system promote the immune recognition of chitosan in blood
and on mucosal surfaces [46]. It is uncertain how these recognition
mechanisms may interfere with the function of chitosan particles.
As in the case of dextran-coated particles, chitosan particles were
successfully applied for the modulation of the function of phagocytic
cells [47]. Therefore, the success of these strategies is likely to involve
the efficient opsonization of the particles. However, in settings not
targeting phagocytic cells, the same processes are likely to present
obstacles to efficient drug delivery.
DNA has proven to be a remarkably versatile polymer for the
formation of nanomaterials with nearly any conceivable structure
[48, 49]. The well-characterized and stable structure of the DNA
double helix provides sufficient rigidity to support the structure
of objects with a size of several nanometers. These structural
properties suggest a potential function of DNA-built structures as
vehicles for drug delivery and controlled release [50]. However, in
spite of several suggestions for applications of such nanomaterials
in vivo , surprisingly little eff ort has been spent on considering
the physiologic response to the injection of DNA with a complex
engineered structure. In the body, DNA is rarely found in the naked
state in healthy individuals but is usually in complex with proteins, in
particular histones. Apparently the DNA-protein complexes may serve
important anti-inflammatory roles [51]. Leukocytes carry receptors,
notably those belonging to the family of Toll-like receptors that bind
DNA and trigger an inflammatory response [52]. The GC-rich DNA of
bacteria is a strong stimulant of the inflammatory response and may
act as an adjuvant in the immune response to microbial antigens.
In cystic fibrosis patients, DNA massively accumulates in the lung
fluid, and there is evidence that the DNA acts as proinflammatory
agent [53]. This suggests, of course, that the application of DNA-
built nanomaterials could induce a similar response. A further
concern over the immune response to injected DNA comes from the
observation that 40-60% of patients suff ering from systemic lupus
erythematosus (SLE) carry antibodies to double-stranded DNA [54].
SLE is a serious chronic autoimmune disorder, which is fatal in some
cases. The formed “anti-self” antibodies, including the antibodies to
 
Search WWH ::




Custom Search