Drug delivery system for active brain targeting - Artificial Cells, Cell Engineering and Therapy - page 418

intranasal administration is associated with several advantages (non-invasiveness,
ease of application, rapid termination of effects in the event of adverse reaction
and avoidance of hepatic first-pass elimination) that encourage its study as a
viable strategy for delivering proteins such as neurotrophic factors into the CNS.
Pharmaceutical applications of chitosan in the form of beads, microspheres
and microcapsules were developed in the early 1990s. Large chitosan
microspheres and beads have typically been used for the prolonged release of
drugs and proteins such as BSA, DNA and brain-derived neurotrophic factor.
Small particle size chitosan microspheres which containing anticancer agents
such as 5-fluorouracil (5-FU) has been described for site-specific delivery. 5-
Fluorouracil-loaded chitosan microspheres were prepared by Zheng et al. (2004)
for intranasal administration. They used the liquid paraffin as the oil phase, and
span 80 as the emuifier; 5-fluorouracil-loaded chitosan microspheres were
achieved by the emulsion chemical crosslink technique. Microspheres have good
shape and narrow size distribution. The drug release profile in vitro could be
described by the Higuichi equation. The results show that chitosan is a good
material

for nasal preparation and has prospective development in the

pharmaceutical field.

17.4 Future trends
The delivery of therapeutic molecules into the BBB has proven to be a major
obstacle in treating brain disorders. In this chapter, many non-invasive CNS
delivery techniques increasing brain uptake have been described. Coupling
nanoparticle/liposome with the specific brain transport target results in
absorptive mediated transcytosis or receptor mediated transcytosis. Applications
of some carriers are shown in Table 17.1. Up to now, the strategies to realize the
active brain targeting by drug delivery system have been focused on the
therapeutic applications, such as thiamine-coated doxorubicin nanoparticles,
ferritin IA modified cisplatin liposomes and 5-FU chitosan microspheres for
brain cancer therapy. Moreover, amphotericin B liposomes modified by RMP-7
could be applied to meningitis therapy. There are also some reports about
antisense gene therapy and other therapeutic agents such as anodyne active
delivering to brain. In addition to therapeutic applications, there are other uses of
these systems. For example, immunoliposomes might be used as diagnostic tools
to localize tumor tissue or amyloid plaques in Alzheimer's disease. Such
applications rely on brain delivery of quantitative amounts of contrast agents
such as magnetoferritin or gadolinium. However, these techniques are compli-
cated because of their chemical modifications and limited by their lower drug
carrying capacity.
While improved brain delivery has been demonstrated, the mechanism of
transport such as NP-BBB circumvention is still theoretical. Further studies are
needed to establish the possible application of such systems in targeting of drugs