Hsieh-Chih Tsai

National Taiwan University of Science and Technology, T’ai-pei, Taipei, Taiwan

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Publications (22)101.33 Total impact

  • Applied Surface Science 09/2014; 313:828-833. · 2.54 Impact Factor
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    ABSTRACT: The purpose of this study was to develop and evaluate thermally responsive copolymers, which contain temperature- and pH-sensitive segments that are either alternating in or grafted onto the main chain, and to exploit their temperature-sensitive properties for ophthalmic drug delivery. Accordingly, two types of thermoresponsive copolymers—a linear poly(acrylic acid-co-N-isopropylacrylamide) random copolymer (PAAc-co-PNIPAAm) and a poly(acrylic acid-g-N-isopropylacrylamide) graft copolymer (PAAc-g-PNIPAAm)—were investigated for their thermosensitive in situ gel formation and potential applications for ophthalmic drug delivery. All the PAAc-g-PNIPAAm graft copolymers, and the linear PAAc-co-PNIPAAm copolymer with low acrylic acid contents, have an LCST of 34 °C; this is close to the surface temperature of the eye and can therefore be utilized for ophthalmic drug delivery. In addition, the PAAc-g-PNIPAAm graft copolymers showed a higher water content than the linear random copolymer; this is due to the high water adsorption ability of PAAc. The drug release dynamics of [3H]-epinephrine as a model showed that the linear random copolymer has a faster drug release, while the graft copolymers showed a more sustained release profile. The Ritger–Peppas model was used to account for the release of the epinephrine diffusion exponent ‘n’ which was in between 0.5 and 0.6. The release of the drug is considered mainly dependent on diffusion but other factors cannot be excluded. We suspected that the dynamics of drug release are determined by the water adsorption ability because high water content results in the formation of a larger capillary network in the polymer matrix, which promotes drug diffusion into the copolymer. The results suggest that PAAc-g-PNIPAAm graft copolymers are potential thermosensitive in situ gel-forming materials for ophthalmic drug delivery.
    J. Mater. Chem. B. 03/2014; 2(14).
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    ABSTRACT: Hydrogels have been developed as artificial extracellular matrixes (ECMs) to mimic native tissue microenvironments for various applications. Unfortunately, poly(N-isopropylacrylamide) (PNIPAAM)-based hydrogels are not suitable for cell culturing and cell sheet preparation. Carbon nanotubes (CNTs), with their mechanical strength and electrical conductivity, have been considered as additives to increase the applicability of hydrogels to cell encapsulation and advance cardiac electrophysiological functions. A simple method for fabrication of PNIPAAM hydrogels interpenetrated with multiwalled CNTs (MWCNTs) as substrates for cell sheet preparation is reported. The results demonstrate that PNIPAAM hydrogels with interpenetrating MWCNTs still exhibit thermosensitive behavior. It is also found that epithelial Madin-Darby canine kidney (MDCK) cells can only attach and proliferate on MWCNT-interpenetrated PNIPAAM hydrogels. Furthermore, the PNIPAAM hydrogels with MWCNTs possess higher elastic moduli and hydrophobicities than those without MWCNTs, suggesting these two characteristics are necessary for the cells to attach to the hydrogel surfaces. Moreover, cell sheets can only be harvested from PNIPAAM hydrogels with MWCNTs because of their high ratio of cell attachment. Thus, this simple method provides sufficient mechanical strength to PNIPAAM hydrogels so that anchorage-dependent cells can be cultivated and provides a superior system for preparing cell sheets.
    Biomaterials 07/2013; · 8.31 Impact Factor
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    ABSTRACT: The kinetics of the curing of sulfone epoxy (SEP) monomers using aromatic and aliphatic amine curing agents was studied via differential scanning calorimetry (DSC). SEP curing is a two-stage process involving SEP/electron donation and electron donation to either aliphatic or aromatic curing agents. The SEP/electron donation curing process occurred readily since semi-electron-withdrawing curing agents are induced by nucleophilic substitution in the first stage. In the second stage, SEP is cured by the semi-electron-withdrawing curing agents. The kinetic parameters of the curing process were determined using a conversional method derived from Ozawa’s and Kissinger’s methods, which are typically used for kinetic analysis of data for thermal treatments. The higher melting points and steric bulk of the aromatic curing agents resulted in higher curing activation energies than for the aliphatic curing agents. The aliphatic curing agents also increased the activation energy of the curing process due to their electron-withdrawing and cross-linking properties as well as the viscosity of the epoxy/amine curing system. Cured SEP/aromatic curing agent materials possessed higher glass transition temperatures than cured SEP/aliphatic curing agent materials.
    Polymer Bulletin 04/2013; 70(4). · 1.49 Impact Factor
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    ABSTRACT: In this study, three types of hybrid nanotubes (NTs), ie, oxidized multiwalled carbon NTs (COOH MWCNTs), heparin (Hep)-conjugated MWCNTs (Hep MWCNTs), and diblock copolymer polyglycolic acid (PGA)-co-heparin conjugated to MWCNTs (PGA MWCNTs), were synthesized with improved biocompatibility and drug-loading capacity. Hydrophilic Hep substituents on MWCNTs improved biocompatibility and acted as nucleus-sensitive segments on the CNT carrier, whereas the addition of PGA enhanced drug-loading capacity. In the PGA MWCNT system, the amphiphilic copolymer (PGA-Hep) formed micelles on the side walls of CNTs, as confirmed by electron microscopy. The PGA system encapsulated the hydrophobic drug with high efficiency compared to the COOH MWCNT and Hep MWCNT systems. This is because the drug was loaded onto the PGA MWCNTs through hydrophobic forces and onto the CNTs by π-π stacking interactions. Additionally, most of the current drug-carrier designs that target cancer cells release the drug in the lysosome or cytoplasm. However, nuclear-targeted drug release is expected to kill cancer cells more directly and efficiently. In our study, PGA MWCNT carriers effectively delivered the active anticancer drug doxorubicin into targeted nuclei. This study may provide an effective strategy for the development of carbon-based drug carriers for nuclear-targeted drug delivery.
    International Journal of Nanomedicine 01/2013; 8:4427-40. · 4.20 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate the use of the biodegradable poly(l-lactide) (PLLA) as a gastro-jejunal tube anchored in the duodenum for duodenal exclusion. PLLA film was fabricated using a hot melting process to a thickness of around 40–50 μm and was then immersed in human gastric juice to estimate the in vitro biodegradability behavior. PLLA film was more biodegradable in human gastric juice than in HCl and PBS. Measurements of weight loss indicated that 60% of original the PLLA was lost after 42 days of incubation. Surface functional group characterization, thermal stability, and surface morphology of the degraded PLLA film in human gastric juice showed that the decomposed sections of the PLLA film were primarily from the amorphous region. The degradation of the PLLA film in human gastric juice began with the erosion of continuous nanocavities in the range of 100–200 nm on the PLLA surface over the course of 21 days. The PLLA film collapsed and spiral PLLA fiber was obtained after 42 days of decomposing in human gastric juice.
    Applied Surface Science 12/2012; 262:89–94. · 2.54 Impact Factor
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    ABSTRACT: An optimized, biodegradable, dual temperature- and pH-responsive micelle system conjugated with functional group Cy5.5 was prepared in order to enhance tumor accumulation. The Dynamic light scattering (DLS) measurements showed that these diblock copolymers form micelle in PBS buffer with a size of around 50 nm by heating of an aqueous polymer solution from below to above the cloud point (CP). Anticancer drug, doxorubicin was incorporated into the inner core of micelle by hot shock protocol. The size and stability of the micelle were controlled by the copolymer composition and is fine tuned to extracellular pH of tumor. The mechanism then caused pH change and at body temperature which induce doxorubicin release from micelles and have strong effects on the viability of HeLa, ZR-75-1, MCF-7 and H661 cancer cells. Our in vivo results revealed a clear distribution of Doxorubicin-loaded mixed micelle (Dox-micelle) and efficiency targeting tumor site with particles increasing size in the tumor interstitial space, and the particles could not diffuse throughout the tumor matrix. In vivo tumor growth inhibition showed that Dox-micelle exhibited excellent antitumor activity and a high rate of anticancer drug in cancer cells by this strategy.
    Biomaterials 03/2012; 33(18):4576-88. · 8.31 Impact Factor
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    ABSTRACT: A two-photon excitation difluoroboron dye activated in the near infrared region for biological image analysis was synthesized in this study. Cell affinity, membrane interaction, and the endocytosis pathway of PAMAM dendrons were investigated using only covalent two-photon dyes (TPD) at the periphery of the PAMAM dendrons. Generation 3 TPD-labeled PAMAM dendrons (BG3) exhibited multivalency binding on the HeLa cell membranes from the cell affinity study in the fixation of HeLa cells. Photo-stimulation on the membrane of the living HeLa cell was observed by confocal optical imaging in situ, using the two-photon model, when incubated with BG3. Analyses of cell membrane integrity via lactate dehydrogenase (LDH) assay confirmed membrane damage at two photon excitation model. However, no variation in the cell was observed using the one-photon excitation model. These results indicated a high degree of dendrons uptake by cells through binding to the cell membrane following the endocytotic pathway. Furthermore, the wide excitation fluorescence spectrum of difluoroboron dye provides dual imaging with which to study the endocytosis of TPD-labeled PAMAM dendrons using a single near infrared laser.
    Journal of Biomedical Materials Research Part A 03/2012; 100(3):746-56. · 2.83 Impact Factor
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    ABSTRACT: The sterically polymer-based liposomal complexes (SPLexes) were formed by cationic polymeric liposomes and pH-sensitive diblock copolymer were studied for their capabilities in improving the stability with high efficiency of siRNA delivery. The SPLexes were formed a dual-shelled structure and uniform size distribution. The PEGylated outer shell could mitigate the phagocytosis and reduce the cytotoxicity. Moreover, the folated SPLexes improved 42.9× accumulation in vitro and 1.7× tumor uptake in vivo in contrast with nonfolated SPLexes. The protonated copolymer at low pH would improve the siRNA released into cytoplasm following SPLexes fusion with the endo/lysosome membrane and inhibited the protein expression to 75.6 ± 4.5% efficiently. Results of this study significantly contribute to efforts to develop lipoplexes based siRNA delivery systems.
    Biomacromolecules 02/2012; 13(3):664-75. · 5.79 Impact Factor
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    ABSTRACT: To understand the effect of photosensitizer (PS) release from graft copolymer based micelles in photodynamic therapy (PDT), the two pH-sensitive and non-pH-sensitive graft copolymers, (poly(N-vinyly caprolactam)-g-poly(D,L-lactide) and poly(N-vinyly caprolactam-co-N-vinyl imidazole)-g-poly(D,L-lactide)), were synthesized and utilized for the encapsulation of protoporphyrin IX (PPIX) for in vitro and in vivo PDT studies. Photochemical internalization (PCI) was utilized to study the localization of pH- and non-pH-sensitive micelles uptake in the lysosome. After non-toxic light treatment, PPIX was found in the nucleus with pH-sensitive micelles, while PPIX was still localized in the lysosomal organism with the non-pH-sensitive micelles, as observed by confocal microscopy. Because the formation of singlet oxygen was observed for the block and graft micelles, dramatic differences in the cell viability could be ascribed to the damage occurring at the region where the PPIX was located. An in vivo study revealed that PPIX-loaded graft and diblock micelles presented prolonged blood circulation and enhanced tumor targeting ability. The PPIX released from g-CIM micelles on tumor site was further proved by ex vivo confocal image. In addition, non-pH-sensitive micelle-treated mice showed a better repression of tumor growth than PPIX-treated mice, which was likely due to the larger amount of PS localized in the tumor region still exhibiting therapeutic effects. Finally, effective PDT-induced inhibition of tumor growth was found in pH-sensitive micelle-treated mice. This work provides insight into PS-loaded graft and diblock micelles for the PDT of tumors.
    Biomaterials 12/2011; 33(6):1827-37. · 8.31 Impact Factor
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    ABSTRACT: This paper develops a non-spherical polymeric micelle using an amphiphilic block copolymer and a porphyrin crystalline structure. The nanoscale polymer micelles were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM), revealing particle sizes of approximately 150 nm with a particular shape in the hexagonal lattice. The shape shows the selective uptake efficacy for the HeLa and macrophage cells, and inhibits phagocytosis against the macrophage.
    Macromolecular Rapid Communications 07/2011; 32(18):1442-6. · 4.61 Impact Factor
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    ABSTRACT: Target geometry for mitigating phagocytosis has garnered considerable attention recently in the drug delivery field. This study examined nanoparticles (NPs) with same volume but different shapes, namely, spherical NPs (SNPs) and hexagonal nanoprisms (HNPs), and analyzed their behaviors in vitro and in vivo. These NPs were constructed with a multifunctional block copolymer component, mPEG-b-P(HEMA-co-histidine-PLA). Geometry of SNPs and HNPs was controlled by adjusting copolymer properties and particle size was controlled by adjusting formulation parameters. Nanoparticle morphology had no effect in mitigating phagocytosis when NP size was 70 nm; however, morphology had a significant effect when NP size was 120 nm. The radioactivity-time curves for (99m)Tc-labeled NPs, fitted by the two-compartment pharmacokinetic model, show that the prolonged plasma distribution half-life of HNPs is indicative in the bloodstream. The in vitro and in vivo studies reveal that dual stealth characteristics, pegylation and hexagonal prism structure, of nanocarriers can be adopted in clinical application for safe and efficient delivery of cancer therapy.
    Journal of Controlled Release 04/2011; 154(1):84-92. · 7.63 Impact Factor
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    ABSTRACT: This article reports a flexible hollow nanoparticles, self-assembling from poly(N-vinylimidazole-co-N-vinylpyrrolidone)-g-poly(d,l-lactide) graft copolymers and methoxyl/functionalized-PEG-PLA diblock copolymers, as an anticancer drug doxorubicin (Dox) carrier for cancer targeting, imaging, and cancer therapy. This multifunctional hollow nanoparticle exhibited a specific on-off switch drug release behavior, owning to the pH-sensitive structure of imidazole, to release Dox in acidic surroundings (intracellular endosomes) and to capsulate Dox in neutral surroundings (blood circulation or extracellular matrix). Imaging by SPECT/CT shows that nanoparticle conjugated with folic acids ensures a high intratumoral accumulation due to the folate-binding protein (FBP)-binding effect. In vivo tumor growth inhibition shows that nanoparticles exhibited excellent antitumor activity and a high rate of apoptosis in cancer cells. After 80-day treatment course of nanoparticles, it did not appreciably cause heart, liver and kidney damage by inactive Dox or polymeric materials. The results indicate that the flexible carriers with an on-off switched drug release may be allowed to accurately deliver to targeted tumors for cancer therapy.
    Biomaterials 03/2011; 32(8):2213-21. · 8.31 Impact Factor
  • Hsieh-Chih Tsai, Toyoko Imae
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    ABSTRACT: Dendrimers consisting of inner core and peripheral shell are well-designed branching architectures with abundant terminal groups. Therefore, the high level of control over dendritic architectures makes dendrimers ideal carriers in biomedical application. In addition, the toxicity of dendrimers mainly comes from the high cationic charge density in the periphery, where charges interact with biological cell membrane and then result in membrane disruption. Two strategies have been utilized to minimize the toxicity of dendrimers: first, selecting neutral or anionic biocompatible dendrimers, and second, masking of peripheral charge by chemical modification. Then the focus of this chapter shifts to biomedical application of biocompatible dendrimers, including drug delivery systems of dendrimers, targeting delivery by dendrimers, and applications of dendrimers for therapy and as imaging agents for inspection.
    Progress in molecular biology and translational science 01/2011; 104:101-40. · 3.11 Impact Factor
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    ABSTRACT: The side-chain polyhedral oligomeric silsesquioxane (POSS)-type epoxy (IPEP) hybrid material was synthesized, and the particle sizes of the POSS segment were less than 5 nm and which particles dispersed uniformly. The 3D AFM microphotograph of the IPEP/DGEBA (diglycidyl ether of bisphenol A) hybrid material exhibited the unique “island” shape, and their XRD pattern displayed amorphous halo structure. The POSS segments of the IPEP could improve the thermal degradation activation energies. Additionally, introduction of the IPEP into the DGEBA could improve the char yield and provide the antioxidation property in the air atmosphere. The char yields of the IPEP/DGEBA hybrid materials could improve from 14.48 to 19.21% and from 0.18 to 1.17% in the nitrogen and air atmospheres, respectively. The IPEP segments could also improve the hardness when the IPEP contents of the IPEP/DGEBA hybrid materials were less than 50 wt %. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
    Journal of Applied Polymer Science 07/2010; 118(6):3723 - 3732. · 1.40 Impact Factor
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    ABSTRACT: Multifunctional mixed micelles that constructed from poly(HEMA-co-histidine)-g-PLA and diblock copolymer PEG-PLA with functional moiety was developed in this study. The mixed micelles had well defined core shell structure which was evaluated by TEM. The functional inner core of poly(HEMA-co-histidine)-g-PLA exhibited pH stimulate to enable intracellular drug delivery and outer shell of PEG-b-PLA with functional moiety Cy5.5 for biodistribution diagnosis and folate for cancer specific targeting were synthesized at the end of the polymer chain. The graft and diblock copolymer self assembled to nanospheres against water with an average diameter below 120 nm without doxorubicin, and an average diameter of around 200 nm when loaded with drug. From drug released study, a change in pH destroy the inner core to lead a significant doxorubicin(Dox) release from mixed micelles. Cellular uptake of folate-micelles was found to be higher than that of non-folate-micelles due to the folate-binding effect on the cell membrane, thereby providing a similar cytotoxic effect to drug only against the HeLa cell line. In vivo study revealed that specific targeting of folate-micelles exhibited cancer targeting and efficiency expression on tumor growth, indicating that multifunctional micelles prepared from poly(HEA-co-histidine)-g-PLA and folate-PEG-PLA have great potential in cancer chemotherapy and diagnosis.
    Biomaterials 03/2010; 31(8):2293-301. · 8.31 Impact Factor
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    ABSTRACT: The sulfonyl epoxy monomer (SEP) was synthesized and further to blend with the diglycidyl ether of bisphenol A (DGEBA). The glass transition temperature (Tg) of the SEP/DGEBA blended materials increased from 103.7 to 163.8°C. The cross-linking density and polymer chain self-association intra-molecular action affected more than that the polymer–polymer intermolecular action (hydrogen bonding) in the SEP blended with the DGEBA materials. The excess stabilization energy in the overall stabilization was only 0.00145% (14.5 ppm), which indicated that the polymer-polymer intermolecular action was weak. The thermal degradation of the SEP segments could form various sulfate derivatives at lower temperature and analyzed by the TGA/GC/Mass. The sulfate derivatives could generate the thermal stable chars, which provided the “shielding effect” and antioxidation property. Additionally, these chars could also improve the protective effect and inhibit the thermal-oxidation decomposition under the air atmosphere. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
    Journal of Applied Polymer Science 01/2010; · 1.40 Impact Factor
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    ABSTRACT: The thiodiphenyl epoxy (THEP) was prepared by the 4,4′-thiodiphenol (THDOL) and the epichlorohydrin (ECH) without using any NaOH or KOH catalysts. The THEP possessed weak hydrogen bonding in the cured THEP/DGEBA system. The intermolecular motion parameters k and q were 0.26 and −168.5, respectively, which determined by the Gordon-Taylor and Kwei equations. The soft sulfide linkage (S) of the THEP degraded at lower temperature than cured DGEBA material, and further to form various thermal stable sulfate derivative chars. The char yields increased from 11.43 to 25.94 wt % and from 0.65 to 1.04 wt % in the nitrogen and air, respectively. Introduction of the THEP into the DGEBA could provide the antioxidation thermal property and improve the thermal stability of the DGEBA epoxy in the air. In the air atmosphere, the activation energies of the second thermal degradation were increased from 66.67 to 103.42 kJ/mol. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
    Journal of Applied Polymer Science 01/2010; · 1.40 Impact Factor
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    ABSTRACT: This study synthesized and characterized a novel series of polyurethanes containing nonlinear optic (NLO) chromophores, which possess different dimensional or various isolation-groups. These chromophores are based on 4-(dicyanomethylene)-2-methyl-6-(p-(dimethylamino)styryl)-4H-pyran (DCM-typed dye). The NLO polyurethane containing a one-dimensional isolation-group of chromophores efficiently enhances thermal stability, but poling efficiency is not always improved as the size of isolation-group increases. The enormous isolation group restrained the mobility of chromophore in the polymer matrix and shows a worsening SH intensity. The maximum second harmonic coefficient (d33 = 68.7 pm/V) is displayed as benzene is attaching to chromophore moieties as isolation-group in this study. Polyurethane containing two-dimensional chromophore shows superior thermal stability due to the large volume required to rotate the chromophore in the polymer matrix. Two-dimensional system exhibits lower SH intensity due to the rigid polymer main chain and twisted conjugated plane. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4937–4949, 2009
    Journal of Polymer Science Part A Polymer Chemistry 08/2009; 47(19):4937 - 4949. · 3.54 Impact Factor
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    ABSTRACT: Mixed micelles formed by critical micelle concentration (Cmc) character's diblock copolymer, and temperature-sensitive character's diblock copolymer were studied for their capabilities in improving stability with and without drug. Experimental results showed that this type of mixed micellar systems possessed complementary effects in adjusting external temperature shift (storage vs. body temperature) and concentration change (dilution after intravenous injection). Therefore, they provided excellent stability as drug carriers. Further results obtained from physicochemical property and drug release kinetics studies demonstrated such systems could also be applied to physiological conditions, in compliance with varied pH environments. We concluded that the newly developed mixed micelles can serve as a potential injectable drug delivery system for anticancer drugs, such as doxorubicin and many others.
    Biomaterials 05/2009; 30(23-24):3961-70. · 8.31 Impact Factor

Publication Stats

145 Citations
101.33 Total Impact Points

Institutions

  • 2010–2014
    • National Taiwan University of Science and Technology
      • • Graduate Institute of Applied Science and Technology
      • • Graduate Institute of Biomedical Engineering
      T’ai-pei, Taipei, Taiwan
  • 2013
    • Taipei Medical University
      T’ai-pei, Taipei, Taiwan
  • 2005–2013
    • National Tsing Hua University
      • Department of Chemical Engineering
      Hsinchu, Taiwan, Taiwan
  • 2011
    • Chang Gung Memorial Hospital
      T’ai-pei, Taipei, Taiwan
  • 2009
    • Chung Yuan Christian University
      • Department of Chemical Engineering
      Taichung, Taiwan, Taiwan