Browsing by Author "Liu, Kun-Ho"

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A flexible drug delivery chip for the magnetically-control led release of anti-epileptic drugs
(2009-11-03)
Huang, Wei-Chen
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Hu, Shang-Hsiu
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Liu, Kun-Ho
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Chen, San-Yuan
;
Liu, Dean-Mo
A flexible drug delivery device was designed and fabricated using electrophoretic deposition of drug-carrying magnetic core-shell Fe(3)O(4) at SiO(2) nanoparticles onto an electrically conductive flexible PET substrate. The PET substrate was first patterned to a desired layout and subjected to deposition. In doing so, a uniform and nanoporous membrane could be produced. After lamination of the patterned membranes, a final chip-like device of thickness less than 0.5 mm is formed that is used for controlled delivery of an anti-epileptic drug, i.e., ethosuximide (ESM). The release of useful drugs can be controlled by directly modulating the magnetic field, and the chip is capable of demonstrating a variety of release profiles (i.e., slow release, sustained release, step-wise release and burst release profiles). These profiles can follow a wide spectrum of patterns ranging from zero to pulsatile release kinetics depending on the mode of magnetic operation. When the magnetic field was removed, the release behavior was instantly ceased, and vice versa. A preliminary in-vivo study using Long-Evans rat model has demonstrated a significant reduction in spike-wave discharge after the ESM was burst released from the chip under the same magnetic induction as in-vitro, indicating the potential application of the drug delivery chip. The flexible and membrane-like drug delivery chip utilizes drug-carrying magnetic nanoparticles as the building blocks that ensure a rapid and precise response to magnetic stimulus. Moreover, the flexible chip may offer advantages over conventional drug delivery devices by improvement of dosing precision, ease of operation, wider versatility of elution pattern, and better compliance. (C) 2009 Elsevier B.V. All rights reserved.
Bioactive TiO2 ultrathin film with worm-like mesoporosity for controlled drug delivery
(2012-04-01)
Chao, Chih-Shin
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Liu, Kun-Ho
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Tung, Wei-Lin
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Chen, San-Yuan
;
Liu, Dean-Mo
Ultrathin mesoporous TiO2 coatings with a wormhole-like architecture were synthesized using evaporation-induced self-assembly method. The morphological and chemical structures of TiO2 films were characterized using small-angle and large-angle X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Fourier transformed infrared spectrometry (FTIR). The films demonstrated a thickness of similar to 120 nm and open-porous nanostructure. By taking advantage of the tortuosity of the worm-like mesoporous architecture associated with the chemistry of the TiO2 film, a sustained drug release using ibuprofen and vancomycin as model molecules from the film was determined. Besides, adhesion behavior of osteoblast cells, together with an in vitro apaptitic formation substantiated the cytocompatibility and bioactivity of the mesoporous TiO2 films. Such combined bioactive and drug-releasing functions of the TiO2 films with worm-like mesoporosity ensure an improved therapeutic performance for potential applications included orthopedics, dentistry, and drug delivery. (C) 2011 Elsevier Inc. All rights reserved.
Drug release behavior of chitosan-montmorillonite nanocomposite hydrogels following electro stimulation
(2008-07-01)
Liu, Kun-Ho
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Liu, Ting-Yu
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Chen, San-Yuan
;
Liu, Dean-Mo
;
材料科學與工程學系
Nanocomposites hydrogel (nanohydrogel) composed of chitosan (CS) and montmorillonite (MMT) were prepared and systematically studied for drug release behavior following electrostimulation. The deterioration of the responsiveness and reversibility of CS upon repeated on-off electrostimulation switching operations are major limitations for clinical applications, as it suffers from too much structural instability for the precise control of the release of drug upon cyclic electrostimulation. To overcome these limitations, an inorganic phase, MMT, was incorporated in the CS matrix to enhance the anti-fatigue property and corresponding long-term stable release kinetics. X-ray diffraction analysis and time-dependent optical absorbance showed that the MMT incorporated into the nanohydrogel exhibited an exfoliated nanostructure. The exfoliated silica nanosheets are able to act as cross-linkers to form a network structure between the CS and MMT, and this difference in the cross-linking density strongly affects the release of vitamin B-12 under electrostimulation. With a lower MMT concentration (1 wt.%), the release kinetics of vitamin B-12 from the nanohydrogel shows a pseudo-zero-order release, and the release mechanism was changed from a diffusion-controlled mode to a swelling-controlled mode under electrostimulation. Further increasing the MMT content reduced both the diffusion exponent n and the responsiveness of the nanohydrogel to electrostimulation. In addition, a consecutively repeated "on" and "off" operation shows that the electroresponsiveness of the nanohydrogel with higher MMT concentrations was reduced, but its anti-fatigue behavior was considerably improved. In this work, the nanohydrogel with 2 wt.% MMT achieved a mechanically reliable and practically desirable pulsatile release profile and excellent anti-fatigue behavior, compared with that of the pure CS. (C) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Effect of clay content on electrostimulus deformation. and volume recovery behavior of a clay-chitosan hybrid composite
(2007-11-01)
Liu, Kun-Ho
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Liu, Ting-Yu
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Chen, San-Yuan
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Liu, Dean-Mo
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材料科學與工程學系
Electrostimulus-responsive hybrid composites composed of chitosan (CS) and clay were successfully developed and systematically characterized. The addition of negatively charged clay as an ionic cross-linker strongly affect the cross-linking density as well as the mechanical property, swelling-deswelling behavior and fatigue property of the hybrids. With lower clay content, the crystallinity of the CS was slightly reduced, resulting in a decrease in the mechanical properties and an increase in the swelling ratio of the hybrid. However, the swelling kinetics were accelerated due to a reduction in CS crystallinity. On the other hand, with increasing clay concentration, the increased cross-linked bonding mechanically reinforced the hybrid beyond the aforementioned adverse effect, to show improved tensile strength and a decrease in the swelling ratio. The voltage-induced deformation of hybrids became more pronounced with increasing applied voltage, but became less pronounced with increasing clay content under an applied electric field. After repeatedly switching the electric field on and off, the higher clay concentration (C-clay > 0.5 wt.%) of the hybrid composites maintained the same capability of deswelling and swelling after more than 10 cycles, compared with both the pure CS film and the hybrid composites with lower clay content (e.g., 0.5 wt.%). Compared with pure CS, a significant improvement in the anti-fatigue property against cyclic electric stimulations of the hybrid was found, which encourages the use of such a new class of hybrid composite in medical and pharmaceutical applications. (C) 2007 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Electrical-Sensitive Nanoparticle Composed of Chitosan and Tetraethyl Orthosilicate for Controlled Drug Release
(2009-02-01)
Liu, Kun-Ho
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Liu, Ting-Yu
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Liu, Dean-Mo
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Chen, San-Yuan
;
材料科學與工程學系
In the present study, the nanoparticles with size of 50-130 nm composed of chitosan (CS) and tetraethyl orthosilicate (TEOS), which showed electrically-control led release profile, were prepared. Myoglobin was encapsulated into the nanoparticles with an encapsulation efficiency as high as 91.5% and a maximum loading capacity of 70.2% that can be achieved. Here, TEOS was hydrolyzed and condensed to form interpenetration network with CS. Increase of TEOS content results in a shift of the release profile from swelling-controlled towards diffusion-controlled mechanism. The "slow-to-burst" and "near-zero" release of the myoglobin can be effectively controlled by applying DC electric field between "on" and "off."
Hollow sphere from amphiphilic chitosan derivatives and method of preparing amiphiphilic chitosan derivative complex for medical use
(2010-04-22)
Chen, San-Yuan
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Liu, Kun-Ho
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Liu, Dean-Mo
A hollow sphere from amphiphilic chitosan derivatives and a method of preparing an amphiphilic chitosan derivative complex for medical use are disclosed, and the hollow sphere from amphiphilic chitosan derivatives comprises: chitosan derivatives represented by the following formula (I), which self-assemble and form a hollow sphere in a solvent;wherein, each R1 is independently hydrogen, C1˜C4 alkyl, C1˜C6 carboxyl, sulfate group, or phosphate group, each R2 is independently hydrogen, C1˜C12 alkyl, C1˜C6 carboxyl, or C2˜C12 acyl group, and m is an integer of 100-2000.
Instantaneous Drug Delivery of Magnetic/Thermally Sensitive Nanospheres by a High-Frequency Magnetic Field
(2008-12-02)
Liu, Ting-Yu
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Hu, Shang-Hsiu
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Liu, Kun-Ho
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Shaiu, Ren-Shiuan
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Liu, Dean-Mo
Novel dual-functional nanospheres composed of magnetic iron oxide nanoparticles embedded in a thermo-sensitive Pluronic F127 (17127) matrix were successfully synthesized by an in situ coprecipitation process. The nanospheres were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy. Experimental observations indicated that the F127 was subjected to a rapid structural change when the magnetic phase caused rapid heating after a short exposure to a high-frequency magnetic field. During the field duration, considerable volume shrinkage of the nanospheres (2.3-fold diameter reduction) was detected. This has been translated to an instantaneous release of a drug, Doxorubicin (DOX), when the DOX was encapsulated within the nanospheres. Such a rapidly responsive release of the DOX from the nanospheres was due to an intimate contact between the nanomagnet and F127, where an effective thermal and mechanical transfer between core and shell phases efficiently took place in the presence of the magnetic field.
Preparation and characterization of smart magnetic hydrogels and its use for drug release
(2006-09-01)
Liu, Ting-Yu
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Hu, Shang-Hsiu
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Liu, Kun-Ho
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Liu, Dean-Mo
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Chen, San-Yuan
The magnetic hydrogels were successfully fabricated by chemically cross-linking of gelatin hydrogels and Fe(3)O(4) nanoparticles (ca. 40-60 nm) through genipin (GP) as cross-linking agent. The cross-sectional SEM observation demonstrates that the Fe(3)O(4) nanoparticles were fairly uniformly distributed in the gelatin matrix. Moreover, in vitro release data reveal that drug release profile of the resulting hydrogels is controllable by switching on or off mode of a given magnetic field. While applying magnetic fields to the magnetic hydrogels, the release rate of vitamin B(12) of the hydrogels was considerably decreased as compared with those when the field was turned off, suggesting a close configuration of the hydrogels as a result of the aggregation of Fe(3)O(4) nanoparticles. Based on this on-&-off mechanism, the smart magnetic hydrogels based on the gelatin-ferrite hybrid composites can be potentially developed for application in novel drug delivery systems. (C) 2006 Elsevier B. V. All rights reserved.
Self-assembled hollow nanocapsule from amphiphatic carboxymethyl-hexanoyl chitosan as drug carrier
(2008-09-09)
Liu, Kun-Ho
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Chen, San-Yuan
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Liu, Dean-Mo
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Liu, Tse-Ying
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材料科學與工程學系
A new type of amphiphilic chitosan, which was synthesized through the use of both hydrophilic carboxymethyl and hydrophobic hexanoyl substitutions, was employed to self-assemble into a hollow nanocapsule in an aqueous environment. Critical aggregation concentration (cac) and zeta potential were experimentally identified for the amphiphilic chitosan (CHC). Both experimental data suggested that the self-assembly behavior of the CHC is fundamentally determined as an interplay between the hydrophobic interaction and the variation of the zeta potential upon hexanoyl substitution, which further influenced the nanostructural evolution of the nanocapsules. Higher hexanoyl substitution promoted larger nanocapsules, ca. 200 nm in diameter, while a reduced zeta potential was correspondingly detected, and vice versa, forming smaller nanocapsules, ca. 20 nm in diameter. The self-assemble mechanism, together with the corresponding nanostructural stability, of this unique CHC nanocapsule was also proposed in terms of intermolecular interaction and thermodynamic reason. By taking the advantage of the self-assemble (or self-aggregation) capability, the CHC was employed for drug encapsulation, i.e., doxorubicin, an anticancer molecule; we found in this preliminary evaluation that it reached an efficiency of 46.8%, and a corresponding drug release from the nanocapsules for a time period exceeded 7 days can be achieved in vitro.
Self-Assembly Behavior and Doxorubicin-Loading Capacity of Acylated Carboxymethyl Chitosans
(2009-09-03)
Liu, Kun-Ho
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Chen, Bo-Rong
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Chen, San-Yuan
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Liu, Dean-Mo
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材料科學與工程學系
A new type of acylated carboxymethyl amphiphilic chitosan (ACC) with the use of acyl chain of varying lengths, from C(2) to C(12), and various degrees of acyl substitution was successfully synthesized and has been characterized in terms of its self-assembly behavior, structural stability, and drug encapsulation. The resulting nanostructure of the ACC nanoaggregates can be well manipulated through a control of hydrophobicity. Structural evolution of the self-assembled nanoaggregates is extensively characterized via (1)H NMR, FTIR, DSC, and TEM. A critical value of the hydrophobic effect, (X(DH) x X(Cn)), i.e., a product of "degree of acyl substitution" and "carbon number of acyl chain", can be employed as an indicator for structural variation of the natioaggregates: when (X(DH) x X(Cn)) exceeded 1.5, the architecture of the nanoaggregates underwent a structural transformation from solid nanoparticle to hollow nanocapsules. The nanoaggregates exhibited an excellent colloidal and structural stability in aqueous medium. An improved affinity toward drug encapsulation, i.e., doxorubicin, can be technically designed according to the amphiphilic nature of the resulting nanoaggregates for drug delivery.
Structural Evolution and Copper-Ion Release Behavior of Cu-pHEMA Hybrids Synthesized In Situ
(2009-11-01)
Liu, Yen-Yu
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Tung, Tsan-Hua
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Liu, Kun-Ho
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Chen, San-Yuan
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Liu, Dean-Mo
A novel Cu-pHEMA hybrid was successfully prepared by in situ photopolymerization of 2-hydroxyethyl methacrylate (HEMA) monomer in the presence of COP copper ions, following an in situ chemical reduction. Experimental observations indicate that intermolecular interactions such as the coupling force and hydrogen bonding between the Cu and the hydroxyl groups further stabilize the hybrid structure to a considerable extent. Localization of the metallic copper particles within the pHEMA network structure as a result of those intermolecular interactions gives rise to the formation of discretely distributed nanocrystallites with particle sizes ranging from 5 to 25 nm in diameter, A crystallographic change of the Cu nanophase from an amorphous-like to a crystalline structure is observed as the H(2)O:HEMA molar ratio increases, upon synthesis, accompanied with an increase in the particle size, A relatively slow and sustained release of the Cu (in the form of cupric ions) from the hybrids was measured for a time period of about 10 days, which also illustrates a Cu(II)-induced proliferation of the endothelial cells over a relatively small range of release rate of the Cu from the hybrids. Such a new type of Cu-loaded hybrid hydrogel is expected to be compatible and may be considered as a candidate biomaterial for biomedical/therapeutic uses.
Study on controlled drug permeation of magnetic-sensitive ferrogels: Effect of Fe3O4 and PVA
(2008-03-20)
Liu, Ting-Yu
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Hu, Shang-Hsiu
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Liu, Kun-Ho
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Liu, Dean-Mo
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Chen, San-Yuan
A PVA-based magnetic-sensitive hydrogel (ferrogel) was fabricated by physical cross-linking through a freezing-thawing method. The influence of the constituting components, i.e., Fe3O4 and PVA, on the magnetic-sensitive behavior of the ferrogels was systematically investigated in terms of permeability coefficient (P), partition coefficient (H), space restriction and magnetization. The results show that, the P value in these ferrogels decreases and displays a magnetic sensitivity when it is subjected to magnetic field (MF), which is correlated with the change of H value. In addition, it was found that although the factor of space restriction or magnetization exerts opposite effect on resulting magnetic-sensitive behavior, the superior magnetic-sensitive behavior was observed for the ferrogels with an optimal composition of 17-34% Fe3O4 and 10-12.5% PVA, and can be well correlated with theoretical calculation from the critical parameters of available free volume per nanoparticle (V-free) and magnetization. A map of magnetic-sensitive behavior was constructed, where a region with relatively stable and highly stimuli-responsive behavior in terms of the concentration of FC3O4 was observed, however, below or above the "saturation" region (17-34% Fe3O4), a reduction in the magnetic-sensitive behavior was detected. The resulting ferrogels can be engineered with a precise control of the opening and closure of pore configuration, which allows a burst release or no-release action of therapeutically active agent to be controlled externally and magnetically. This suggests that this type of ferrogel can be considered as a class of novel magnetically-tunable drug delivery system. (c) 2007 Elsevier B.V. All rights reserved.
Synergistic hierarchical silicone-modified polysaccharide hybrid as a soft scaffold to control cell adhesion and proliferation
(2014-08-01)
Huang, Wei-Chen
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Liu, Kun-Ho
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Liu, Ta-Chung
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Liu, Dean-Mo
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Chen, San-Yuan
In this study, a new type of polydimethylsiloxane-modified chitosan (PMSC) amphiphilic hydrogel was developed as a soft substrate to explore cellular responses for dermal reconstruction. The hydrogel wettability, mechanical stiffness and topography were controllable through manipulation of the degree of esterification (DE) between hydrophobic polydimethylsiloxane (PDMS) and hydrophilic N,O-(carboxymethyl)-chitosan (NOCC). Based on microphase separation, the incorporation of PDMS into NOCC increased the stiffness of the hybrid through the formation of self-assembled aggregates, which also provided anchor sites for cell adhesion. As the DE exceeded 0.39, the size of the PDMS-rich aggregates changed from nanoscale to microscale. Subsequently, the hierarchical architecture resulted in an increase in the tensile modulus of the hybrid gel up to fourfold, which simultaneously provided mechano-topographic guidance and allowed the cells to completely spread to form spindle shapes instead of forming a spherical morphology, as on NOCC (DE = 0). The results revealed that the incorporation of hydrophobic PDMS not only impeded acidic damage resulting from NOCC but also acted as an adhesion modification agent to facilitate long-term cell adhesion and proliferation on the soft substrate. As proved by the promotion on long-term type-I collagen production, the PMSC hybrid with self-assembled mechano-topography offers great promise as an advanced scaffold material for use in healing applications. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Synthesis and characterization of mesoporous Gd(2)O(3) nanotube and its use as a drug-carrying vehicle
(2010-09-01)
Chang, Yen-Po
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Liu, Kun-Ho
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Chao, Chih-Shin
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Chen, San-Yuan
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Liu, Dean-Mo
Gd(2)O(3) nanotubes were constructed for the first time by assembling highly crystalline Gd(2)O(3) nanoparticles through the use of combined soft template and sol-gel methods. Amphiphilic block copolymer was used as structure-directing agent and gadolinium isopropoxide as inorganic precursor in non-aqueous solution. The amphiphilic copolymer molecules are known to undergo self-organization above a critical micelle concentration, forming micellular architecture that further provides a structurally ordered active site for the nucleation and growth of Gd monomers. The resulting self-assembly of the Gd(2)O(3) nanocrystals led to the formation of Gd(2)O(3) tubular nanostructure after pyrolytic removal of the template. Transmission electron microscopy analysis indicated a mesoporous channel array along the [1 1 0] direction of the nanotubes where the wall of nanotube is well organized by the assembly of a highly crystalline framework of Gd(2)O(3) nanocrystals. This Gd(2)O(3) nanotube exhibited weak superparamagnetic property and was found to be able to carry and elute a model molecule, i.e. ibuprofen (IBU), in a controllable manner via an external magnetic field. The mechanism of IBU release from the nanotubes with and without the use of magnetic stimulus was proposed. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Synthesis and characterization of mesoporous Gd2O3 nanotube and its use as a drug-carrying vehicle
(2010-09-01)
Chang, Yen-Po
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Liu, Kun-Ho
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Chao, Chih-Shin
;
Chen, San-Yuan
;
Liu, Dean-Mo
Gd2O3 nanotubes were constructed for the first time by assembling highly crystalline Gd2O3 nanoparticles through the use of combined soft template and sol-gel methods. Amphiphilic block copolymer was used as structure-directing agent and gadolinium isopropoxide as inorganic precursor in non-aqueous solution. The amphiphilic copolymer molecules are known to undergo self-organization above a critical micelle concentration, forming micellular architecture that further provides a structurally ordered active site for the nucleation and growth of Gd monomers. The resulting self-assembly of the Gd2O3 nanocrystals led to the formation of Gd2O3 tubular nanostructure after pyrolytic removal of the template. Transmission electron microscopy analysis indicated a mesoporous channel array along the [1 1 0] direction of the nanotubes where the wall of nanotube is well organized by the assembly of a highly crystalline framework of Gd2O3 nanocrystals. This Gd2O3 nanotube exhibited weak superparamagnetic property and was found to be able to carry and elute a model molecule, i.e. ibuprofen (IBU), in a controllable manner via an external magnetic field. The mechanism of IBU release from the nanotubes with and without the use of magnetic stimulus was proposed. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Temperature-Sensitive Nanocapsules for Controlled Drug Release Caused by Magnetically Triggered Structural Disruption
(2009-02-24)
Liu, Ting-Yu
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Liu, Kun-Ho
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Liu, Dean-Mo
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Chen, San-Yuan
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Chen, I-Wei
Self-assembled nanocapsules containing a hydrophilic core and a crosslinked yet thermosensitive shell are successfully prepared using poly(ethylene-oxide) poly(propylene-oxide)-poly(ethylene-oxide) block copolymers, 4-nitrophenyl chloroformate, gelatin, and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. The core is further rendered magnetic by incorporating iron oxide nanoparticles via internal precipitation to enable externally controlled actuation under magnetic induction. The spherical nanocapsules exhibit a hydrophilic-to-hydrophobic transition at a characteristic but tunable temperature reaching 40 degrees C, triggering a size contraction and shrinkage of the core. The core content experiences very little leakage at 25 degrees C, has a half life about 5 h at 45 degrees C, but bursts out within a few minutes under magnetic heating due to iron oxide coarsening and core/shell disruption. Such burst-like response may be utilized for controlled drug release as illustrated here using a model drug Vitamin B12.