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Chih-Chang Chu

Publications and source records attributed to Chih-Chang Chu.

14 recordsLinked to original sources

Effect of solvent mixture on the properties of temperature- and pH-sensitive polysaccharide-based hydrogels.

Novel partially biodegradable, temperature- and pH-sensitive polysaccharide-based hydrogels (NDF) were synthesized from modified dextran (dextran-maleic acid, Dex-MA) and N-isopropylacrylamide precursors over a wide range of mixed solvent ratios of dimethyl formamide (DMF) to water. N-Isopropylacrylamide monomers were chosen to impart thermo-responsive capability to Dex-MA, while Dex-MA was chosen to impart pH-responsive capability to N-isopropylacrylamide. The pH-sensitive precursor (Dex-MA) was synthesized by reacting dextran with maleic anhydride in the presence of triethylamine catalyst. To fabricate multi-stimuli hybrid hydrogel networks, both Dex-MA and N-isopropylarylamide precursors were photo-cross-linked via UV at a fixed Dex-MA to N-isopropylarylamide feed ratio over a wide range of DMF to water mixed solvent ratios. The newly synthesized PNIPAAm/Dex-MA hybrid hydrogels (NDF) were characterized by Fourier transform infrared spectroscopy for chemical structure determination, differential scanning calorimetry for thermal analysis and scanning electron microscopy for morphological study. The properties of the hybrid hydrogels, such as thermo-induced deswelling, pH-sensitivity, ionic strength sensitivity and thermo-reversibility, were also examined. The swelling data obtained clearly showed that newly synthesized multi-stimuli NDF hydrogels exhibited multi-responsive capability to external stimuli like temperature and pH. The morphological data obtained showed that this new class of PNIPAAm/Dex-MA hybrid hydrogels had a wide range of unique three-dimensional porous network structures that depended on the composition ratio of the mixed DMF/water solvent during cross-linking reaction. This unique but versatile 3D porous network structures of NDF hydrogels were correlated to the data from thermo-induced swelling behavior, thermo-reversibility, pH-dependent swelling and ionic strength sensitivity.

Acrylic Resins↗

Fabrication and characterization of a smart drug delivery system: microsphere in hydrogel.

In this contribution, a novel smart drug delivery system (DDS) consisting of hydroxyl-functionalized glycerol poly(epsilon-caprolactone) (PGCL)-based microspheres and poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was developed for prolonged and sustained controlled drug release. Various amounts PGCL-based microspheres were incorporated physically into temperature sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel to form the novel DDSs. Resulting DDSs were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and compression modulus measurements to investigate the morphological, thermal, and mechanical properties. The temperature dependence of swelling ratio and response kinetics upon heating or cooling were also investigated to understand the smart properties, i.e., temperature sensitive properties of these DDSs. Finally, ovalbumin (OVA), used as the model drug, was loaded into PGCL-based microspheres to examine and compare the effects of controlled release at different temperature (22 and 37 degrees C) of these novel smart DDSs.

Acrylic Resins↗

Synthesis, characterization and controlled drug release of thermosensitive IPN-PNIPAAm hydrogels.

A method was developed to prepare thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with an interpenetrating polymer network (IPN) structure for the purpose of improving its mechanical properties, response rate to temperature and sustained release of drugs. Although the differential scanning calorimetry data exhibited similarly lower critical solution temperature (LCST) between IPN- and non-IPN-PNIPAAm hydrogels, an increase in the glass transition temperature (Tg) of the IPNs relative to the normal PNIPAAm hydrogel was observed. In addition, the mechanical properties of the IPNs were greatly improved when compared with the normal PNIPAAm hydrogel. The interior morphology of the IPN-PNIPAAm hydrogels was revealed by scanning electron microscopy (SEM); the IPN hydrogels showed a fibrillar-like porous network structure that normal PNIPAAm did not have. Furthermore, by measuring the temperature dependence of the swelling ratio and deswelling kinetics, these IPN hydrogels also exhibited improved intelligent characteristics (e.g., controllable faster response rate) that depended on the composition ratio of the two network components. From the applications viewpoint, the effects of a shrinking-reswelling cycle around the LCST on the properties of the IPN hydrogels were examined to determine if these properties would be stable for potential applications. Bovine serum albumin was chosen as the model protein for examining its release from the IPNs at different temperatures. The release data suggested that an improved controlled release could be achieved by the IPN-PNIPAAm hydrogels without losing their intelligent properties.

Absorption↗

Synthesis and characterization of partially biodegradable, temperature and pH sensitive Dex-MA/PNIPAAm hydrogels.

The objective of the study is to impart temperature and pH-sensitive capabilities to polysaccharide-based hydrogels, so that they can change their swelling property upon external stimulation like temperature or/and pH. Dextran was chosen as the model polysaccharide compound for such a demonstration. A novel class of dextran-maleic anhydride (Dex-MA)/poly(N-isopropylacrylamide) hybrid hydrogels was designed and synthesized by UV photocrosslinking. The dextran-based precursor (Dex-MA) was prepared by substituting the hydroxyl groups in Dex by MA. This Dex-MA precursor was then photocrosslinked with a known temperature sensitive precursor (N-isopropylacrylamide, NIPAAm) to form hybrid hydrogels having a wide range of composition ratio of Dex-MA to NIPAAm precursors. Due to the biodegradable nature of dextran, these Dex-MA/PNIPAAm hybrid hydrogels are partially biodegradable. These smart hybrid hydrogels were characterized by Fourier transform infrared spectroscopy for structural determination, differential scanning calorimertry for thermal property, maximum swelling ratio, swelling kinetics, temperature response kinetics, and effect of pH. The data obtained clearly show that these new smart hybrid hydrogels were responsive to the external changes of temperature as well as pH. The magnitude of smart and hydrogel properties of these hybrid hydrogels were found to depend on the feed composition ratio of the two precursors. By changing the composition ratio of these two precursors, the phase transition temperature (lower critical solution temperature) of the hybrid hydrogels could also be adjusted to be or near the body temperature for the potential applications in bioengineering and biotechnology fields.

Absorption↗

Synthesis and characterization of partially biodegradable and thermosensitive hydrogel.

A partially biodegradable and thermosensitive hybrid hydrogel network (DAN series) based on dextran-allylisocyanate (Dex-AI) and poly(N-isopropylacrylamide) (PNIPAAm) was synthesized via UV photocrosslinking. These hybrid hydrogels were characterized in terms of their chemical structure, thermal, mechanical, morphological and temperature-induced swelling properties. The effect of the composition ratio of Dex-AI to PNIPAAm on such properties were examined. The differential scanning calorimetry data show that this Dex-AI/PNIPAAm hybrid network has an increased lower critical solution temperature (LCST) and glass transition temperature (Tg) with an increase in the Dex-AI content. The interior morphology of these hybrid hydrogels revealed a decreased porous microstructure with an increase in the Dex-AI content in the hybrid network. Furthermore, if the Dex-AI composition became too high, a distinctive network structure with two different microporous structures appeared. The mechanical properties of these hybrid hydrogels also increased with an increase in the Dex-AI content. The temperature dependence of the swelling ratio, the deswelling kinetics as well as the reswelling kinetics was also characterized by gravimetric method. When comparing with a normal PNIPAAm hydrogel, these Dex-AI/PNIPAAm hybrid networks, due to the presence of Dex-AI moiety, also show improved temperature-induced intelligent properties, such as the faster and controllable response dynamics, which may find promising applications in a wide variety of fields, such as biomedical and bioengineering fields.

Absorbable Implants↗

Thermosensitive PNIPAAm cryogel with superfast and stable oscillatory properties.

Through copolymerization/crosslinking in dimethyl sulfoxide (DMSO) at temperature below the melting point of DMSO, we demonstrated a novel poly(N-isopropylacrylamide) (PNIPAAm) hydrogel with regularly oriented micromatrix; the superfast/stable oscillatory hydration-dehydration character of this hydrogel would find wide applications in biomedical field.

Journal Article↗

Thermoresponsive hydrogel with rapid response dynamics.

Intelligent hydrogels, particularly poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogels, have attracted extensive interest because the soft wet hydrogels can change their shapes in response to the small changes of environmental factors like temperature. In order to fully make use of this unique property of PNIPAAm-based hydrogels, the response rates of the PNIPAAm hydrogels have to be improved since the dynamics property is critical to certain applications of this material. In this paper, the thermo-sensitive PNIPAAm hydrogels were successfully synthesized by carrying out the polymerization of N-isopropylacrylamide monomer in vacuum (-100 kPa) at room temperature (22 degrees C). The resultant hydrogel has tremendously improved shrinking rate as well as the large volume changes upon temperature stimulation when comparing with the normal PNIPAAm hydrogel. The SEM micrographs revealed that the improved properties were attributed to the macroporous network structure generated during the synthesis under vacuum.

Journal Article↗

Synthesis, characterization and drug release from three-arm poly(epsilon-caprolactone) maleic acid/poly(ethylene glycol) diacrylate hydrogels.

A biodegradable polymer network hydrogel with both hydrophobic and hydrophilic components was synthesized and characterized. The hydrophobic and hydrophilic components were a three-arm poly(epsilon-caprolactone) maleic acid (PGCL-Ma, as the hydrophobic constituent) and poly(ethylene glycol) diacrylate macromer (PEGDA, as a hydrophilic constituent), respectively. These two polymers were chemically photo-crosslinked to generate a three-dimensional network structure, which were characterized by FT-IR, DSC and SEM. The swelling property of the networks was studied in phosphate-buffered saline (PBS, pH 7.4). The results of this study showed that a wide-range swelling property was obtained by changing the composition ratio of PGCL-Ma to PEGDA. The in vitro release of bovine serum albumin (BSA) from these hydrogels as a function of the PEGDA to PGCL-Ma composition ratio and incubation time was examined and we found that the incorporation of PEGDA into PGCL-Ma increased the initial burst release of BSA. As the PEGDA component increased, the rate of formation of a loose three-dimensional (3D) network structure increased; consequently, the sustained rate and extent of BSA release increased. We suggest that the release of BSA was controlled by both diffusion of BSA through swelling of the hydrophilic phase during an early stage and degradation of the hydrophobic phase during a late stage; and that the relative magnitude of diffusion versus degradation controlled release depended on composition ratio and immersion time.

Animals↗

Biodegradable dextran-polylactide hydrogel networks: their swelling, morphology and the controlled release of indomethacin.

Biodegradable polymer hydrogel networks based on hydrophilic dextran derivative of allyl isocyanate (dex-AI) and hydrophobic poly (D,L) lactide diacrylate macromer (PDLLAM) were synthesized, and their swelling and morphological properties were studied. During a 2-day incubation, the higher the PDLLAM composition in the hydrogel, the slower the swelling as well as the lower the extent of swelling were. A 3D porous network structure was observed by scanning electron microscope. The rate of formation of this 3D porous network structure depended on the hydrophilicity of the components, their composition ratio, and the degradation time. The highly hydrophilic dex-AI component facilitated the formation of this 3D porous network structure at an earlier immersion period, while the degradability of the PDLLAM component would make this 3D porous network structure more open at a later immersion period. Indomethacin, a low molecular weight and moderately hydrophobic drug, was incorporated into the hydrogels for the release study in pH 7.4 phosphate buffer solution at 37 degrees C. The release kinetics suggested, as the PDLLAM composition increased, the indomethacin diffusion coefficient (D) and release half life time (t(1/2)) decreased, while the release index n increased. The controlled release mechanism was determined by the combination of three factors: the rate and degree of formation of swelling-induced 3D porous structure in the hydrogel, the hydrolytic degradation of PDLLAM components, and the hydrophobic interaction between PDLLAM and IDM.

Biocompatible Materials↗

Biodegradation of hydrophilic-hydrophobic hydrogels and its effect on albumin release.

The objective of this study was to examine the effects of composition ratio of a new class of bicomponent biodegradable hydrogels and the molecular weights of the constituents on the hydrolytic degradability of the hydrogels and their release of bovine serum albumin (BSA). Biodegradable hydrogels were prepared from dextran derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) over a wide range of dex-AI to PDLLAM composition ratio. The results obtained indicated that the hydrolytic degradation of these biodegradable hydrogels could be controlled by adjusting the composition ratio of dex-AI to PDLLAM or by changing their molecular weights. Along with the hydrogel degradation, water content of the hydrogels changed, and 3D porous network structure was observed. Generally, as the PDLLAM composition in the hydrogels increased, the rate of weight loss increased due to the hydrolytic degradation of the PDLLAM. The increase in molecular weights of either dex-AI or PDLLAM would decrease the degradation rate of the dex-AI/PDLLAM hydrogels. BSA release data correlated well with the hydrogel degradation profiles, suggesting that the extent and rate of BSA release would be mainly controled by hydrogel degradation. As the PDLLAM composition in the hydrogel increased, the extent and rate of BSA release also increased. An increase in the molecular weights of the hydrogel constituents, however, led to a decrease in BSA release.

Journal Article↗

Thermal and mechanical properties of biodegradable hydrophilic-hydrophobic hydrogels based on dextran and poly (lactic acid).

The thermal and mechanical properties of a new family of biodegradable hydrogels made of photocrosslinked dextran derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) were studied. The changes of thermal and mechanical properties of the dex-AI/PDLLAM hydrogels as functions of dex-AI to PDLLAM composition ratio and immersion time in phosphate buffer solution at 37 degrees C were also investigated. Thermal property data showed that the chemical modification, crosslinking, swelling and hydrolytic degradation affected the glass transition and melting temperatures. Based on thermal data, no phase separation was observed in the bicomponent dex-AI/PDLLAM hydrogels. Mechanical property data showed that, by changing the composition ratio, dex-AI/PDLLAM hydrogels having a wide range of dry and swollen compression moduli could be obtained. The moduli of the dex-AI/DPLLAM hydrogels in dry state decreased with an increase in the PDLLAM composition due to the reduction in glass transition temperature of the hydrogels. The loss of mechanical strength in buffer solutions was attributed to the swelling-induced formation of 3D porous network structure in the early stage of immersion and the hydrolytic degradation of the PDLLAM in the late stage via the chain scission of ester linkages located in the PDLLAM backbone. Because swelling and degradation were composition dependent, the magnitude of the loss of mechanical strength was also composition-dependent.

Journal Article↗

In-vivo biocompatibility evaluation of stents coated with a new biodegradable elastomeric and functional polymer.

BACKGROUND: In-stent restenosis may be prevented by impregnating an antiproliferative agent in a polymer from a stent platform. This approach requires both an antiproliferative agent effective in small doses and a biocompatible polymer. METHODS: A series of new biodegradable elastomeric poly(ester-amide)(co-PEA) polymers having functional carboxyl groups for drug conjugation were synthesized from non-toxic building blocks. The in-vivo biocompatibility was tested in porcine coronary arteries, by comparing the polymer-coated stents with bare metal stents in 10 pigs. RESULTS: All animals survived until sacrifice 28 days later and follow-up angiography prior to sacrifice revealed identical diameter stenosis (21 +/- 23%) in both groups. Histology confirmed similar injury scores (0.34 +/- 0.34 compared with 0.34 +/- 0.32), inflammatory reaction (1.18 +/- 0.38 compared with 1.11 +/- 0.32) and area stenosis (26 +/- 17% compared with 28 +/- 22%). CONCLUSIONS: This study suggests that the newly developed copoly(ester-amide) elastomers may be suitable for stent-based local drug delivery.

Absorbable Implants↗

In vitro release behavior of insulin from biodegradable hybrid hydrogel networks of polysaccharide and synthetic biodegradable polyester.

The controlled release of insulin from a series of biodegradable hybrid hydrogel network containing dextran derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) over a wide range of composition ratio was investigated. Laser confocal scanning microscope was used to understand the insulin dispersion and release mechanism in the hydrogels. We found that the dispersion of insulin in the hydrogel network appeared to become less homogeneous as the PDLLAM composition in the hydrogel increased. The increase in hydrogel degradability imparted by PDLLAM incorporation shifted the hydrogel to a more open structure at a later release time, which facilitated the release rate and extent of insulin. From the result of release kinetics study (i.e., diffusion coefficient), insulin release occurred through diffusion and degradation controlled mechanisms. In addition, a comparison of the release characteristics of indomethacin, insulin and bovine serum albumin from the hydrogel network showed that the following parameters determined the release kinetics: drug molecular weight and size, hydrogel swellability and degradability, drug solubility in water and the hydrophobic interaction between drugs and the hydrogel network.

Biocompatible Materials↗