Hsing-Wen Sung

National Tsing Hua University, Hsin-chu-hsien, Taiwan, Taiwan

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Publications (148)920.22 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: As a cationic polysaccharide, chitosan (CS) has been identified for its potential use as a non-viral vector for exogenous gene transfection. However, owing to their electrostatic interactions, CS complexes may cause difficulties in gene release upon their arrival at the site of action, thus limiting their transfection efficiency. In this work, an attempt is made to facilitate the release of a gene by incorporating a negatively-charged poly(γ-glutamic acid) (γPGA) into CS complexes in order to diminish their attractive interactions. The mechanisms of exploiting γPGA to enhance the transfection efficiency of CS complexes are elucidated. The feasibility of using this CS/γPGA-based system for DNA or siRNA transfer is explored as well. Additionally, potential of the CS/γPGA formulation to deliver disulfide bond-conjugated dual PEGylated siRNAs for multiple gene silencing is also examined. Moreover, the genetic use of pKillerRed-mem, delivered using complexes of CS and γPGA, to express a membrane-targeted KillerRed as an intrinsically generated photosensitizer for photodynamic therapy is described.
    Journal of Controlled Release 04/2014; · 7.63 Impact Factor
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    ABSTRACT: As is widely suspected, lysolipid dissociation from liposomes contributes to the intravenous instability of ThermoDox® (Lysolipid liposomes), thereby impeding its antitumor efficacy. This work evaluates the feasibility of a thermoresponsive bubble-generating liposomal system without lysolipids for tumor-specific chemotherapy. The key component in this liposomal formulation is its encapsulated ammonium bicarbonate (ABC), which is used to actively load doxorubicin (DOX) into liposomes and trigger a drug release when heated locally. Incubating ABC liposomes with whole blood results in a significantly smaller decrease in the retention of encapsulated DOX than that by Lysolipid liposomes, indicating superior plasma stability. Biodistribution analysis results indicate that the ABC formulation circulates longer than its Lysolipid counterpart. Following the injection of ABC liposome suspension into mice with tumors heated locally, decomposition of the ABC encapsulated in liposomes facilitates the immediate thermal activation of CO2 bubble generation, subsequently increasing the intratumoral DOX accumulation. Consequently, the antitumor efficacy of the ABC liposomes is superior to that of their Lysolipid counterparts. Results of this study demonstrate that this thermoresponsive bubble-generating liposomal system is a highly promising carrier for tumor-specific chemotherapy, especially for local drug delivery mediated at hyperthermic temperatures.
    ACS Nano 04/2014; · 12.03 Impact Factor
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    ABSTRACT: Cell transplantation via direct intramuscular injection is a promising therapy for patients with ischemic diseases. However, following injections, retention of transplanted cells in engrafted areas remains problematic, and can be deleterious to cell-transplantation therapy. In this Progress Report, a thermoresponsive hydrogel system composed of aqueous methylcellulose (MC) blended with phosphate-buffered saline is constructed to grow cell sheet fragments and cell bodies for the treatment of ischemic diseases. The as-prepared MC hydrogel system undergoes a sol-gel reversible transition upon heating or cooling at ≈32 °C. Via this unique property, the grown cell sheet fragments (cell bodies) can be harvested without using proteolytic enzymes; consequently, their inherent extracellular matrices (ECMs) and integrative adhesive agents remain well preserved. In animal studies using rats and pigs with experimentally created myocardial infarction, the injected cell sheet fragments (cell bodies) become entrapped in the interstices of muscular tissues and adhere to engraftment sites, while a minimal number of cells exist in the group receiving dissociated cells. Moreover, transplantation of cell sheet fragments (cell bodies) significantly increases vascular density, thereby improving the function of an infarcted heart. These experimental results demonstrate that cell sheet fragments (cell bodies) function as a cell-delivery construct by providing a favorable ECM environment to retain transplanted cells locally and consequently, improving the efficacy of therapeutic cell transplantation.
    Advanced Healthcare Materials 01/2014;
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    ABSTRACT: Chemotherapy-induced neutropenia often increases the likelihood of life-threatening infections. In this study, a nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with diethylene triamine pentaacetic acid (γPGA-DTPA) was prepared for oral delivery of granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor. The therapeutic potential of this NP system for daily administration of G-CSF to treat neutropenia associated with chemotherapy was evaluated in a rat model. In vitro results indicate that the procedures of NP loading and release preserved the structural integrity and bioactivity of the G-CSF molecules adequately. Those results further demonstrated the enzymatic inhibition activity of γPGA-DTPA towards G-CSF against intestinal proteases. Additionally, the in vivo biodistribution study clearly identified accumulations of G-CSF in the heart, liver, bone marrow, and urinary bladder, an indication of systemic absorption of G-CSF; its relative bioavailability was approximately 13.6%. Moreover, significant glucose uptake was observed in bone marrow during G-CSF treatment, suggesting increased bone marrow metabolism and neutrophil production. Consequently, neutrophil count in the blood increased in a sustained manner; this fact may help a patient's immune system recover from the side effects of chemotherapy.
    Biomaterials 01/2014; · 8.31 Impact Factor
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    ABSTRACT: Oxidative stress and reduced pH are involved in many inflammatory diseases. This study describes a nanoparticle-based system that is responsive to both oxidative stress and reduced pH in an inflammatory environment to effectively release its encapsulated curcumin, an immune-modulatory agent with potent anti-inflammatory and antioxidant capabilities. Due to the presence of Förster resonance energy transfer between curcumin and the carrier, this system also allowed us to monitor the intracellular release behavior. The curcumin released upon triggering could efficiently reduce the excess oxidants produced by the lipopolysaccharide (LPS)-stimulated macrophages. The feasibility of using the curcumin-loaded nanoparticles for anti-inflammatory applications was further validated in a mouse model with ankle inflammation induced by LPS. The results of these studies demonstrate that the proposed nanoparticle system is promising for treating oxidative stress-related diseases.
    ACS Nano 01/2014; · 12.03 Impact Factor
  • Ko-Jie Chen, Hsiang-Fa Liang, Hsing-Wen Sung
    Journal of Controlled Release 11/2013; 172(1):e46-7. · 7.63 Impact Factor
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    ABSTRACT: The objective of this study was to synthesize a cationic microbubble (CMB) conjugated with an antibody against matrix metalloproteinase 2 (CMBMMP2) to increase microbubble accumulation and gene transfection in the infarcted myocardium and to restore ventricular function following an ischemic insult. We previously reported that our CMBs enhanced the efficiency of gene transfection following ultrasound-targeted microbubble destruction (UTMD) in rodent hearts. Therefore, we conjugated a thiolated MMP2 antibody to the PEG chains on the CMB surface, which was verified by fluorescent microscopy. Rats underwent ischemia/reperfusion injury 3 days prior to UTMD delivery of the control or Timp3 plasmid. The CMBMMP2 improved microbubble accumulation in the infarct region, with 57% more contrast intensity compared to the non-conjugated CMB. UTMD-mediated CMBMMP2 delivery of the Timp3 gene significantly increased TIMP3 protein levels in the infarct scar and border zone at 3 days post-UTMD compared to delivery by the non-conjugated CMB. Both MMP2 and MMP9 activity were reduced in the CMBMMP2Timp3 group, which resulted in smaller and thicker infarcts and improved cardiac function. UTMD therapy with this CMBMMP2 provides an efficient platform for the targeted delivery of factors intended to preserve ventricular structure and improve cardiac function after ischemic injury.
    Biomaterials 10/2013; · 8.31 Impact Factor
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    ABSTRACT: Photodynamic therapy (PDT) has received considerable attention as a therapeutic treatment for cancer and other diseases; however, it is frequently accompanied by prolonged phototoxic reaction of the skin due to slow clearance of synthetic photosensitizers (PSs) administered externally. This study was designed to investigate the genetic use of pKillerRed-mem, delivered using complexes of chitosan (CS) and poly(γ-glutamic acid) (γPGA), to intracellularly express a membrane-targeted KillerRed protein that can be used as a potential PS for PDT. Following transfection with CS/pKillerRed/γPGA complexes, a red fluorescence protein of KillerRed was clearly seen at the cellular membranes. When exposed to green-light irradiation, the KillerRed-positive cells produced an excessive amount of reactive oxygen species (ROS) in a time-dependent manner. Data from viability assays indicate that ROS have an important role in mediating KillerRed-induced cytotoxicity, apoptosis, and anti-proliferation, suggesting that KillerRed can be used as an intrinsically generated PS for PDT treatments. Notably, the phototoxic reaction of KillerRed toward cells gradually became negligible over time, presumably because of its intracellular degradability. These experimental results demonstrate that this genetically encoded KillerRed is biodegradable and has potential for PDT-induced destruction of diseased cells.
    Biomaterials 10/2013; · 8.31 Impact Factor
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    ABSTRACT: Cell transplantation for therapeutic neovascularization holds great promise for treating ischemic diseases. This work prepared three-dimensional aggregates of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs) with different levels of internal hypoxia by a methylcellulose hydrogel system. We found that few apoptosis occurred in these cell aggregates, despite developing a hypoxic microenvironment in their inner cores. Via effectively switching on the hypoxia-inducible factor-1α-dependent angiogenic mechanisms, culturing the internally hypoxic HUVEC/cbMSC aggregates on Matrigel resulted in formation of extensive and persistent tubular networks and significant upregulation of pro-angiogenic genes. As the level of internal hypoxia created in cell aggregates increased, the robustness of the tubular structures developed on Matrigel increased, and expression levels of the pro-angiogenic genes also elevated. Transplantation of hypoxic HUVEC/cbMSC aggregates into a mouse model of an ischemic limb significantly promoted formation of functional vessels, improved regional blood perfusion, and attenuated muscle atrophy and bone losses, thereby rescuing tissue degeneration. Notably, their therapeutic efficacy was clearly dependent upon the level of internal hypoxia established in cell aggregates. These analytical results demonstrate that by establishing a hypoxic environment in HUVEC/cbMSC aggregates, their potential for therapeutic neovascularization can be markedly enhanced.
    Biomaterials 09/2013; · 8.31 Impact Factor
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    ABSTRACT: Current insulin therapy via subcutaneous administration can lead to occasional hypoglycemia and peripheral hyperinsulinemia, due to its nonphysiological route. This study evaluates the feasibility of using bovine insulin and exendin-4 in a form of combination therapy, as orally delivered by nanoparticles composed of chitosan and poly(γ-glutamic acid) (CS/γPGA NPs), to control blood glucose levels in rats with type 2 diabetes mellitus (T2DM) undergoing the oral glucose tolerance test. Experimental results indicate that CS/γPGA NPs could enhance the intestinal paracellular permeation; consequently, the exogenous bovine insulin and exendin-4 could be delivered into the liver and pancreas, where they could elicit their glucoregulatory activities. In response to the stimulus of exogenously delivered bovine insulin and the endogenously secreted rat insulin stimulated by the ingested exendin-4, significant glucose utilizations were found in the cardiac and skeletal muscles, resulting in the glucose-lowering effect. Owing to its synergic stimulation effects, the hypoglycemic effect of oral ingestion of NPs containing bovine insulin and exendin-4 was significantly greater than that of the group solely treated with insulin NPs. Above results demonstrate that oral combination therapy with bovine insulin and exendin-4 improves the modulation of blood glucose levels in T2DM rats, making it highly promising for treating those T2DM patients not adequately controlled by the current insulin therapy.
    Biomaterials 07/2013; · 8.31 Impact Factor
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    ABSTRACT: Cell-based therapeutic neovascularization is a promising method for treating ischemic disorders. In this work, human umbilical vein endothelial cells (HUVECs) were thoroughly premixed with cord-blood mesenchymal stem cells (cbMSCs) and cultivated to form three-dimensional (3D) cell aggregates for cellular cardiomyoplasty. In the in vitro study, tubular networks were formed at day 1 after the co-culturing of dissociated HUVECs and cbMSCs on Matrigel; however, as time progressed, the grown tubular networks regressed severely. Conversely, when 3D cell aggregates were grown on Matrigel, mature and stable tubular networks were observed over time, under the influence of their intensive cell‒extracellular matrix (ECM) interactions and cell‒cell contacts. 3D cell aggregates were transplanted into the peri-infarct zones of rats with myocardial infarction (MI) via direct intramyocardial injection. Based on our pinhole single photon emission computed tomography (SPECT) myocardial-perfusion observations, echocardiographic heart-function examinations and histological analyses, the engrafted 3D cell aggregates considerably enhanced the vascular densities and the blood flow recovery in the ischemic myocardium over those of their dissociated counterparts, thereby reducing the size of perfusion defects and restoring cardiac function. These results demonstrate that the intramuscular delivery of 3D cell aggregates of HUVECs/cbMSCs can be a valuable cell-based regenerative therapeutic strategy against MI.
    Journal of Controlled Release 07/2013; · 7.63 Impact Factor
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    ABSTRACT: Many human diseases carry at least two independent gene mutations, further exacerbating clinical disorders. In this work, disulfide bond-conjugated dual PEGylated siRNAs were synthesized, capable of specifically targeting and silencing two genes simultaneously. To achieve efficient delivery, the conjugated siRNAs were formulated with the cationic chitosan together with an anionic polymer, poly(γ-glutamic acid) (γPGA), to form a ternary complex. Experimental results indicate that the incorporated γPGA could significantly enhance their intracellular delivery efficiency, allowing for reduction of the disulfide bond-conjugated PEGylated siRNAs delivered to the PEGylated siRNAs in the reductive cytoplasmic environment. The PEGylated siRNAs could more significantly increase their enzymatic tolerability, effectively silence multiple genes, and prolong the duration of their gene silencing capability than the unmodified siRNAs could. Silencing of different genes simultaneously significantly contributes to the efforts to treat multiple gene disorders, and prolonged duration of gene silencing can reduce the need for frequent administrations.
    Biomaterials 06/2013; · 8.31 Impact Factor
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    ABSTRACT: This work examined the feasibility of preparing a pH-responsive nanoparticle (NP) system composed of chitosan and poly(γ-glutamic acid) conjugated with ethylene glycol tetraacetic acid (γPGA‒EGTA) for oral insulin delivery in diabetic rats during an oral glucose tolerance test (OGTT). OGTT has been used largely as a model to mimic the period that comprises and follows a meal, which is often associated with postprandial hyperglycemia. Based on Förster resonance energy transfer (FRET), this work also demonstrated the ability of γPGA‒EGTA to protect insulin from an intestinal proteolytic attack in living rats, owing to its ability to deprive the environmental calcium. Additionally, EGTA-conjugated NPs were effective in disrupting the epithelial tight junctions, consequently facilitating the paracellular permeation of insulin throughout the entire small intestine. Moreover, results of positron emission tomography and computer tomography demonstrated the effective absorption of the permeated insulin into the systemic circulation as well as promotion of the glucose utilization in the myocardium, and skeletal muscles of the chest wall, forelimbs and hindlimbs, resulting in a significant glucose-lowering effect. Above results indicate that as-prepared EGTA-conjugated NPs are a promising oral insulin delivery system to control postprandial hyperglycemia and thus may potentially prevent the related diabetic complications.
    Journal of Controlled Release 05/2013; · 7.63 Impact Factor
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    ABSTRACT: Fucoidan has the ability to inhibit angiogenesis by human umbilical vein endothelial cells (HUVECs). However, a major clinical limitation is its poor oral availability because fucoidan is a hydrophilic macromolecule. In this study, an oversulfation reaction of fucoidan has been performed to enhance its anti-angiogenic activities. The synthesized, oversulfated fucoidan (OFD) was characterized by Fourier transformed infrared (FT-IR) spectroscopy. The oversulfate content of OFD was estimated to be 41.7% by using a BaCl2 gelatin method. Nanoparticles (NPs) composed of chitosan (CS) and OFD were prepared by a polycation-polyanion complex method. The mean particle sizes of prepared CS/OFD NPs were in the range of 172-265 nm with a negative or positive surface charge, depending on the relative concentrations of CS to OFD used. The self-assembled NPs with pH-sensitive characteristics and could be used as a pH-switched nanocarrier for oral delivery of the antiangiogenic macromolecule, OFD, in response to simulated gastrointestinal (GI) tract media. Evaluation of test NPs in enhancing the intestinal paracellular transport of OFD suggested that the NPs with a positive surface charge could transiently open the tight junctions between Caco-2 cells and thus increased the paracellular permeability. Tight junction opening and restoration were examined by monitoring the redistribution of ZO-1 tight junction proteins using confocal laser scanning microscopy (CLSM). The transported OFD significantly inhibit the tube formation of HUVECs via competitive binding of OFD and bFGF to bFGF receptors (bFGFR).
    Acta biomaterialia 04/2013; · 5.09 Impact Factor
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    ABSTRACT: Based on a porcine model with surgically created myocardial infarction (MI) as a pre-clinical scheme, this study investigates the clinical translation of cell sheet fragments of autologous mesenchymal stem cells (MSCs) for cellular cardiomyoplasty. MSC sheet fragments retaining endogenous extracellular matrices are fabricated using a thermo-responsive methylcellulose hydrogel system. Echocardiographic observations indicate that transplantation of MSC sheet fragments in infarcted hearts can markedly attenuate the adverse ventricular dilation and preserve the cardiac function post MI, which is in contrast to the controlled groups receiving saline or dissociated MSCs. Additionally, histological analyses suggest that administering MSC sheet fragments significantly prevents the scar expansion and left ventricle remodeling after MI. Immunohistochemistry results demonstrate that the engrafted MSCs can differentiate into endothelial cells and smooth muscle cells, implying that angiogenesis and the subsequent regional perfusion improvement is a promising mechanism for ameliorating post-infarcted cardiac function. However, according to the data recorded by an implantable loop recorder, the transplanted MSCs may provoke arrhythmia. Nevertheless, the proposed approach may potentially lead to the eventual translation of MSC-based therapy into practical and effective clinical treatments.
    Biomaterials 03/2013; · 8.31 Impact Factor
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    ABSTRACT: Tea catechins, the major polyphenolic compounds in green tea are potent antioxidant with numerous attributed health benefits. However, oral administration of the oxidation-sensitive compounds is limited by the harsh environment of the gastrointestinal tract (GIT) and become an important challenge. In this study, self-assembled nanoparticles composed of chitosan (CS) and an edible polypeptide, poly(γ-glutamic acid) (γ-PGA) were prepared for the delivery of tea catechins. The tea catechins-loaded nanoparticles were pH-responsive and demonstrated different tea catechins release profiles in simulated gastrointestinal tract (GI tract) media. Sustained free radical (DPPH and ABTS+) scavenging assays showed that the antioxidant activity of tea catechins was retained by the nanoparticles. The nanoparticles with a positive surface charge could transiently open the tight junctions between Caco-2 cells and thus increased the paracellular transport of tea catechins. These results demonstrate that CS/γ-PGA nanoparticles can be effective as a carrier for oral delivery of tea catechins with effective antioxidant activity.
    Food Hydrocolloids 01/2013; 30(1):33–41. · 3.49 Impact Factor
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    ABSTRACT: The therapeutic effectiveness of chemotherapy is optimal only when tumor cells are subjected to a maximum drug exposure. To increase the intratumoral drug concentration and thus the efficacy of chemotherapy, a thermoresponsive bubble-generating liposomal system is proposed for triggering localized extracellular drug delivery. The key component of this liposomal formulation is the encapsulated ammonium bicarbonate (ABC), which is used to create the transmembrane gradient needed for a highly efficient encapsulation of doxorubicin (DOX). At an elevated temperature (42 °C), decomposition of ABC generates CO2 bubbles, creating permeable defects in the lipid bilayer that rapidly release DOX and instantly increase the drug concentration locally. Because the generated CO2 bubbles are hyperechogenic, they also enhance ultrasound imaging. Consequently, this new liposomal system encapsulated with ABC may also provide an ability to monitor of a temperature-controlled drug delivery process.
    ACS Nano 12/2012; · 12.03 Impact Factor
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    ABSTRACT: The proximity of cells in three-dimensional (3D) organization maximizes the cell-cell communication and signaling that are critical for cell function. In this study, 3D cell aggregates composed of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs) were used for therapeutic neovascularization to rescue tissues from critical limb ischemia. Within the cell aggregates, homogeneously mixed HUVECs and cbMSCs had direct cell-cell contact with expressions of endogenous extracellular matrices and adhesion molecules. Although dissociated HUVECs/cbMSCs initially formed tubular structures on Matrigel, the grown tubular network substantially regressed over time. Conversely, 3D HUVEC/cbMSC aggregates seeded on Matrigel exhibited an extensive tubular network that continued to expand without regression. Immunostaining experiments show that, by differentiating into smooth muscle cell (SMC) lineages, the cbMSCs stabilize the HUVEC-derived tubular network. The real-time PCR analysis results suggest that, through myocardin, TGF-β signaling regulates the differentiation of cbMSCs into SMCs. Transplantation of 3D HUVEC/cbMSC aggregates recovered blood perfusion in a mouse model of hindlimb ischemia more effectively compared to their dissociated counterparts. The experimental results confirm that the transplanted 3D HUVEC/cbMSC aggregates enhanced functional vessel formation within the ischemic limb and protected it from degeneration. The 3D HUVEC/cbMSC aggregates can therefore facilitate the cell-based therapeutic strategies for modulating postnatal neovascularization.
    Biomaterials 12/2012; · 8.31 Impact Factor
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    ABSTRACT: We synthesized a cationic microbubble (CMB) with the aim of enhancing its DNA-carrying capacity to improve targeted gene transfection of the ischemic heart for cardiac regeneration. We previously reported that ultrasound-targeted microbubble destruction (UTMD) employing the commercial Definity microbubble (MB) successfully transfected genes into rodent hearts, but the transfection efficiency was modest. We synthesized a CMB and compared its DNA-carrying capacity and reporter gene transfection efficiency with the Definity MB. The CMB bound 70% more plasmid DNA than the Definity MB. UTMD-mediated gene delivery with the CMB enhanced both transfection efficiency and gene expression. In vivo studies assessed the ability of the CMB to deliver the therapeutic AKT gene to the ischemic rat myocardium and evaluated the effects on apoptosis, angiogenesis, and cardiac function. AKT transfection with the CMB reduced infarct size (p < 0.05), increased infarct thickness (p < 0.05), reduced apoptosis (p < 0.05), increased vascular density (p < 0.05), and improved cardiac perfusion and function (p < 0.05) compared to the Definity MB. Delivery of AKT with the CMB resulted in greater cardiac functional improvements compared to the Definity MB. UTMD therapy with this CMB provides an efficient platform for the targeted delivery of factors required to regenerate the ischemic heart and preserve cardiac function.
    Biomaterials 12/2012; · 8.31 Impact Factor
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    ABSTRACT: Calcium (Ca(2+)) has a crucial role in maintaining the intestinal protease activity and in forming the apical junctional complex (AJC) that preserves epithelial barrier function. Ethylene glycol tetraacetic acid (EGTA) is a Ca(2+)-specific chelating agent. To maintain the concentration of this chelator in areas where enzyme inhibition and paracellular permeation enhancement are needed, this study synthesized a poly(γ-glutamic acid)-EGTA conjugate (γPGA-EGTA) to form nanoparticles (NPs) with chitosan (CS) for oral insulin delivery. Results of our molecular dynamic (MD) simulations indicate that Ca(2+) ions could be specifically chelated to the nitrogen atoms, ether oxygen atoms, and carboxylate oxygen atoms in [Ca(EGTA)](2-) anions. By chelating Ca(2+), γPGA-EGTA conferred a significant insulin protection effect against proteases in intestinal tracts isolated from rats. Additionally, calcium depletion by γPGA-EGTA could stimulate the endocytosis of AJC components in Caco-2 cell monolayers, which led to a reversible opening of AJCs and thus increased their paracellular permeability. Single-photon emission computed tomography images performed in the biodistribution study clearly show the (123)I-insulin orally delivered by CS/γPGA-EGTA NPs in the heart, aorta, renal cortex, renal pelvis and liver, which ultimately produced a significant and prolonged hypoglycemic effect in diabetic rats. The above results confirm that this γPGA-EGTA conjugate is a promising candidate for oral insulin delivery.
    Journal of Controlled Release 11/2012; · 7.63 Impact Factor

Publication Stats

3k Citations
920.22 Total Impact Points

Institutions

  • 2000–2014
    • National Tsing Hua University
      • Department of Chemical Engineering
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2009–2012
    • National Cheng Kung University
      • Department of Chemical Engineering
      Tainan, Taiwan, Taiwan
  • 2008–2010
    • Vanung University
      臺中市, Taiwan, Taiwan
  • 2004–2009
    • Taichung Veterans General Hospital
      臺中市, Taiwan, Taiwan
  • 2002–2008
    • National Yang Ming University
      T’ai-pei, Taipei, Taiwan
  • 2007
    • Industrial Technology Research Institute
      Hsin-chu-hsien, Taiwan, Taiwan
  • 2005
    • KLE College of Pharmacy
      Belgaum, Karnātaka, India
  • 1999–2000
    • National Central University
      • Department of Chemical & Materials Engineering
      Taoyuan City, Taiwan, Taiwan