Biomedical Engineering Reference
In-Depth Information
showing higher fluorescence intensity in tumors than in other major organs (Figure 3.30d)
at 3 days after i.v. administration indicate that CPT-HGC nanoparticles are preferentially
accumulated in tumor tissue rather than in normal organs. The highest NIR fluorescence
intensity was observed in tumor tissue and the NIR fluorescence intensity was 23 times
higher than those of other organs (Figure 3.30e).
The enhanced therapeutic potencies of nanoparticles are mainly due to passive target-
ing to tumor sites, based on the EPR effect, which is attributed to high vascularization
and enhanced permeability of tumor blood vessels combined with limited lymphatic
clearance of macromolecules from the tumor environment [234,235]. Nanoparticles should
retain drugs while circulating, thereby preventing premature drug release before the
nanoparticles accumulate in the tumor. To increase therapeutic efficacy, nanoparticle
design must allow for drug release, and therefore subsequent increases in drug concen-
tration, in tumor tissues. In addition, drug delivery in nanoparticles substantially reduces
adverse side effects by virtue of the relatively low doses of drugs (compared to free drug
doses) required [236,237].
3.4.4.5 Chitosan Hydrogels for Antitumors
The formation of hydrogels from polymers using noncovalent cross-linking is a useful
method of preparing hydrogels for drug delivery. These gels are likely to be biocompatible
as gel formation does not require the use of organic solvents or chemical reactions, which
may be potentially deleterious to the drug load. Such physically cross-linked chitosan-
based gels are formed by exploiting either hydrogen bonding or hydrophobic attractions.
Hwang et al. [238] and Martin et al. [239] have focused on the use of pendant hydrophobic
groups to achieve noncovalent cross-linking. Palmitoylglycol chitosan (GCP, Figure 3.31)
hydrogel has been evaluated as an erodible controlled release system for the delivery of
hydrophilic macromolecules. Fluorescein isothiocyanate (FITC)-dextran, and/or amphiphilic
derivatives Gelucire 50/13 and vitamin E [d-α-tocopherol poly(ethyleneglycol)succinate]
were used as model macromolecules. Hydration and erosion were governed by the hydro-
phobicity of the gel and the presence of amphiphilic additives. The controlled release of
FITC-dextran was governed by the hydrophobicity of the gel. In a subsequent study, GCP
hydrogel was evaluated for buccal delivery of the hydrophobic drug denbufylline [240].
The buccal route has been advocated as a possible means for administration of drugs that
undergo extensive hepatic first-pass metabolism or that are susceptible to degradation in
the GI tract.
O
OH
OH
O
O
N
O
O
14
O
O
O
O
O
Glycol
chitosan
HO
HO
NH
NH 2
x
1-x
O
30
Figure 3.31
Scheme of the synthesis of palmitoyl glycol chitosan.
Search WWH ::




Custom Search