Biomedical Engineering Reference
In-Depth Information
the bioavailability of poorly water-soluble molecules [204]. The smaller-sized particles seem to
have more efficient interfacial interaction with the cell membrane as compared to larger-sized
particles due to the endocytosis of small-sized particles. Small-sized particles can improve
the efficacy of particle-based oral drug delivery systems [205]. The use of particle size reduc-
tion to increase the oral bioavailability of drugs has been recognized [206].
Nanoparticles can prolong the blood half-life of drugs and increase efficacy by i.v. injec-
tion [207]. If particles between 30 and 100 nm are intravenously applied, the liver elimi-
nates larger particles faster from the bloodstream compared to smaller particles. Thus, the
larger the particles, the shorter their plasma half-life period [208]. As a result, with increas-
ing particle size, the efficacy of chitosan nanoparticles administrated by IV injection
decreased significantly. The TWI of chitosan nanoparticles (40 nm) against S-180 and H22
was 49% and 54%, respectively [209].
Measurements of mucoadhesiveness using small intestinal brush border membrane
(
BBM
)
surfaces
: Surface plasma resonance (SPR; BIAcoreX, GE Healthcare, UK) analysis was used
to estimate the intestinal adhesion of LMWC and LMWC-Docetaxel (DTX). Ileal BBM ves-
icles from the small intestines of SD rats (180-200 g, fasted overnight) were prepared by the
previously reported method (Ca
2+
precipitation method) [210,211]. The size distributions of
BBM vesicles were observed using electronic light scattering (ELS8000, Otsuka Electronics,
Osaka, Japan). Ileal BBM vesicles were immobilized on an L1 sensor chip. For binding
measurements, LMWC and LMWC-DTX (Figure 3.24) (each 1 and 2 mM) were dissolved
in running buffer (10 mM HEPES and 150 mM NaCl, pH 7.4) and injected for 5 min at a
flow rate of 2 L/min [212,213].
The solubility of DTX in water was measured to be approximately 67 μg/mL, whereas
that of LMWC-DTX was approximately 1.4 mg/mL of DTX equivalent. As expected, the
solubility of DTX was increased by approximately 200-fold after conjugation with LMWC.
This improved water solubility enables elimination of Tween 80-based formulation, so that
saline can be used to dissolve LMWC-DTX. Moreover, the parent DTX is released from the
HOH
2
C
HOH
2
C
O
O
HO
O
HO
O
x
n-x
HN :
NH
2
O
O
HO
OH
O
Me
O
O
N
H
3
C
O
O
H
3
C
H
O
CH
3
Ph
O
AcO
HO
O
O
Ph
Figure 3.24
Scheme of the complex of LMWC-DTX.
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