Key Engineering Materials
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Paper Title Page
Abstract: The double-layered microspheres play an important role in controlling drug delivery for
pharmaceutical application, because of the low initial burst compared with single-layered spheres
and targetable delivery to specific organ. But it has drawback in loading drug and controlling size.
In this study, we developed double-layered spheres using relatively simple oil-in-water (O/W)
solvent evaporation method using bovine serum albumin (BSA) as water-soluble protein and
poly(D,L-lactide-co-glycolide) (PLGA). BSA/PLGA double-layered microspheres were fabricated
using O/W solvent evaporation method and investigated the specific character of double-layered
microspheres according to the kind of surfactants. In SEM observation, double layered microsphere
had spherical shape and smooth surface without pores. And the double layered microsphere using
O/W solvent evaporation method was transparency because of slow evaporation of solvent. In
fluorescent observation, we observed the fluorescent core in the double-walled spheres composed of
FITC-BSA and PLGA using fluorescent observation. In the case of polyvinylalcohol as emulsifier,
the yield was better than gelatin. As decreased concentration of PLGA, the size of double-layered
microspheres deceased.
513
Abstract: Therapeutic angiogenesis by localized delivery of angiogenic factors is a promising
approach to treat patients with cardiovascular disease and to engineer large tissues. Vascular
endothelial growth factor (VEGF) is the most common and biologically active form of the VEGF
family, which acts as a mitogen to endothelial cells and is capable of specific binding to heparin.
However, when VEGF is administered via bolus injection, it can be widely distributed, and its
concentration is likely to be within the effective window for only a short time period due to rapid
degradation. Delivery of angiogenic factors, using controlled drug delivery strategies, offers great
potential to promote angiogenesis at a specific site while reducing the unwanted side effects that
may occur with systemic delivery. We now report on the sustained release of VEGF from alginate
gels, modified with a heparin-binding peptide. Briefly, a small peptide with the sequence of
G5K(βA)FAKLAARLYRKA, which is known to specifically interact with heparin, was chemically
conjugated to alginate, and the peptide-modified alginate formed gels after mixing with heparin and
VEGF. The release rate of VEGF from the gels slowed in vitro for over 45 days, compared with
release from non-modified alginate gels. This result suggests potential applications of alginate gels
in promoting angiogenesis for therapeutic purposes, as well as for tissue engineering.
517
Abstract: Polyethylenimine-graft-poly(L-lactide-co-glycolide) (PEI-g-PLGA) block copolymers
were prepared by a ring-opening polymerization of L-lactide and glycolide using PEI as a macroinitiator
and stannous octoate as a catalyst in dimethylformamide at 100 °C. The molecular structure
of the block copolymers was evaluated with 1H-NMR, and the molecular weight of the block
copolymers was determined with gel permeation chromatography. The thermal properties were
investigated using differential scanning calorimetery and thermogravimetric analysis. The zetapotential
of the pDNA/copolymer complexes was evaluated with dynamic laser light scattering.
Cytotoxicity and gene transfection efficiency of PEI-g-PLGA were tested in vitro using human
embryonic kidney 293 cell culture. The pDNA/copolymer complexes (N/P = 10) showed a lower
zeta-potential than pDNA/PEI25kDa complex, suggesting the lower toxicity of the
pDNA/copolymer complexes. The copolymer composition was found to significantly affect the
gene transfection efficiency of the pDNA/copolymer complexes. The copolymers with lower
contents of PLGA showed higher gene transfection efficiency. These results indicate that these
block copolymers are promising candidates for gene delivery vehicles, featuring good
biocompatibility, potential biodegradability, and relatively high gene transfection efficiency.
521
Abstract: A novel protocol to control the molecular degradation of hyaluronic acid (HA) was
successfully developed. HA has a different conformational structure in water and in organic solvent,
and the carboxyl group of HA is known to be the recognition site of CD44 and hyaluronidase.
Based on these facts, HA was chemically modified in the mixed solvent of water and ethanol by
grafting adipic acid dihydrazide (ADH) to the carboxyl group of HA, which resulted in high degree
of ADH modification up to 85 mol% with controlled degradation of HA by hyaluronidase. The
degradation controlled HA-ADH will be assessed for various tissue engineering applications.
525
Abstract: We have developed a novel protocol to prepare a branch-type PEGylation for a long
acting formulation of aptamer therapeutics. A symmetric doubler phosphoramidite and the
following amine modified phosphoramidite synthon were introduced to the final sequence of antithrombin
aptamer, as a model for various aptamer therapeutics. The conventional linear PEGylation
reagents were conjugated to the terminal amine groups of oligonucleotide to prepare the branchtype
PEGylated anti-thrombin DNA aptamer. The PEGylated aptamer exhibited the improved
bioactivity to retard the occlusive thrombus formation in vitro.
529
Abstract: The purpose of the present study was to develop a polymer film loaded with drug to
effectively prevent pin tract infection. It was found that the polymer, poly ethylene-co-vinyl acetate
blended with tetrahydrofuran, showed better flexibility and deformability than the other polymers:
poly caprolactone18 and poly caprolactone44. Polymer films, poly ethylene-co-vinyl acetate, were
divided into five testing groups dependent on the loading concentration of rifampici (5, 10, 15, and
20 wt %). The surface morphology of polymer films was examined by a scanning electron
microscopy. It was found that the concentration of drug was a main factor to determine the
roughness of the film. Considering the roughness of polymer films, 5 wt % of rifampicin might be
the maximum concentration for further applications. Hence, the antibiotic drug-loaded polymer
films were manufactured by mixing poly(ethylene-co-vinylacetate) and tetrahydrofuran with
rifampicin(antibiotic drug). The film cast was designed as a shape of disk (inner Ø5mm and outer
Ø20mm) to be suitable for pins for external fixation in orhtopaedics. The drug-loaded polymer
solvent, the amount of 0.6cc, was molded into the disk-shaped film and dried into a airtight box at
15°C for 24 hrs. The drug release characteristics(1, 2, 3, 4 and 5 wt%) were examined as a function
of soaking time in phosphate buffered saline (PBS, 10 ml) using an enzyme-linked immunosorbent
assay. Rifampicin was linearly released for first 100 hrs(~4 days) for all antibiotic drug-loaded
polymer films. Afterward, the drug was released at a slower pace as a function of square root of
time until 1000 hrs (~40 days). This slow drug release can be explained by their hydrophobic
characteristics of poly ethylene-co-vinyl acetate and rifampicin. The antibiotic drug-loaded polymer
film can be intrinsically able to prevent the bacteria adhesion by wrapping the pin track area, and
perform active and effective infection-resistant by a sustained antibiotic-release.
533
Abstract: Effectiveness of epidermal growth factor receptor(EGFR)-targeted, long circulating and
temperature-sensitive liposomes(TSLs) is described using sterically stabilized gemcitabine-loaded
liposomes in vitro. Development of long-circulating formulation of TSLs with the EGFR antibody
attached was designed to expect an increase in binding and drug delivery efficiency to the target
cells such as non-small cell lung cancer cells(A549) and human pancreatic carcinoma cells(PANC-
1). New TSLs were prepared using DPPC:DMPC:DSPC(4:1:1 molar ratio) by the REV method.
Differential scanning calorimetry of TSLs showed the phase-transition around 402. Release of a
self-quenching fluorescent probe, calcein, from TSLs was studied for evaluation of temperaturesensitivity.
Anti-proliferation effect of gemcitabine-loaded TSLs and antibody-conjugated TSLs in
A549 and PANC-1 were higher than free drug. We conclude that sterically stabilized
immunoliposomes exhibited good stability, ability to recognize target cells, and higher potency.
Further studies, including in vivo animal study, are under investigation.
537
541
Abstract: The bioactivities of titanium oxide film on titanium surface received from different
chemical treatment methods were studied in SBF in vitro and mechanically and histologically
investigated in vivo. Three groups of titanium specimens were prepared: untreated titanium(S),
acid-alkali treated titanium (H), and acid-alkali and heat-treated titanium(X). The oxide film of X
surface resulted in more apatite formation and significantly higher strength of the interface between
the samples and bone than those of the other titanium groups. The surface of the acid-alkali treated
titanium and that further treated by heat treatment had higher bioactivity and stronger bone-bonding
ability.
545
Abstract: Elastic modulus and mechanical property of Ti-Nb-O alloys prepared by arc melting and
subsequent water quenching were investigated in order to correlate the result of microstructural
observations and phase stability. In quenched state, it was evidently observed that the volume fraction
of bcc-structured β phase increased with increasing content of oxygen, and the occurrence of
intermediate ω phase was suppressed in the present Ti-Nb based alloys. This microstructural result
was supported by changes in martensite transformation temperature, which decreased with increasing
content of oxygen within the chemical composition range investigated. Therefore, it is suggested that
oxygen plays a role as a β phase stabilizer rather than α stabilizer in metastable β Ti-Nb alloys. Yield
strength increased with increasing content of oxygen without a large consumption of ductility in
Ti-Nb based alloys with Nb content of 24% while elongation value decreased with increasing content
of oxygen in Ti-Nb based alloys with Nb content of 28%. The variation of mechanical property was
explained by the phase stability, phase formation and microstructure in correlation with oxygen and
Nb content.
549