The Experts below are selected from a list of 2922 Experts worldwide ranked by ideXlab platform
Patricia L. Chang - One of the best experts on this subject based on the ideXlab platform.
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Biological properties of photocrosslinked Alginate Microcapsules
Journal of biomedical materials research. Part B Applied biomaterials, 2005Co-Authors: Feng Shen, R.m. Cornelius, John L. Brash, Pasquale Cirone, Ronald F. Childs, Patricia L. ChangAbstract:An alternative form of gene therapy using recombinant cell lines delivering therapeutic products encapsulated in Alginate hydrogel has proven effective in treating many murine models. The lack of long-term capsule stability has led to a new strategy to reinforce the Microcapsules with a photopolymerized interpenetrating covalent network of N-vinylpyrrolidone (NVP) and sodium acrylate. Here the properties for potential application in gene therapy are reported. In assessing potential toxicity of the unpolymerized residues, HPLC showed that even after 1 week of washing, no toxic monomers could be detected. Their ability to sustain cell growth was monitored with growth of the encapsulated cells in vitro and in vivo. Although the initial photopolymerization caused significant cell damage, the cells were able to recover normal growth rates thereafter. After implanting into mice, the NVP-modified capsules showed a high level of biocompatibility as measured by hematological and biochemical functional tests. There was also no difference in the amount and type of plasma proteins adsorbing to the NVP-modified and the classical Alginate capsules, thus indicating their similar biological compatibility. Both in vitro and in vivo tests confirmed that the NVP-modified capsules were more resistant to osmotic stress than the Alginate Microcapsules. Furthermore, when applied to the treatment of a murine model of human cancer by delivering encapsulated cells secreting angiostatin, the NVP-modified Microcapsules suppressed tumor growth as successfully as the regular Alginate Microcapsules. In conclusion, the covalently modified Microcapsules have shown a high level of biocompatibility, safety, increase in stability, and clinical efficacy for use as immunoisolation devices in gene therapy.
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A novel method to enhance the stability of Alginate-poly-L-lysine-Alginate Microcapsules
Journal of biomaterials science. Polymer edition, 2005Co-Authors: Maggie Sanju Wang, Ronald F. Childs, Patricia L. ChangAbstract:Implantation of microencapsulated recombinant cells is an alternative approach to gene therapy. These genetically-engineered cells enclosed in Microcapsules to deliver therapeutic recombinant products have been effective in treating several murine models of human diseases. However, the most commonly used Microcapsules fabricated from Alginate ionically cross-linked with calcium suffer from loss of long-term mechanical stability. We now report on a method to improve their stability by introducing additional polymers to provide covalent linkages via photopolymerization. Vinyl monomers and a photoinitiator were allowed to diffuse into the initially formed calcium–Alginate Microcapsules. In situ photopolymerization in the presence of sodium acrylate and N-vinylpyrrolidone substantially enhanced their mechanical strength. After four months of storage in saline, > 70% of these capsules remained intact in the osmotic pressure test, while the un-modified Alginate Microcapsules totally disintegrated. Tests of thei...
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Quantitative chemical mapping of sodium acrylate- and N-vinylpyrrolidone-enhanced Alginate Microcapsules.
Journal of biomaterials science. Polymer edition, 2005Co-Authors: Tohru Araki, Patricia L. Chang, Feng Shen, Maggie Sanju Wang, Adam P. Hitchcock, Ronald F. ChildsAbstract:Alginate Microcapsules enclosing recombinant cells secreting therapeutic products have been used successfully to treat several murine models of human diseases. The mechanical and chemical properties of these Alginate capsules can be improved by the addition and in situ photopolymerization of sodium acrylate and N-vinylpyrrolidone in the Alginate capsule. The purpose of this modification was to form additional covalent cross-links. In this work we have used scanning transmission X-ray microscopy (STXM) to probe the nature and location of the chemical modifications in the modified capsules by comparison with unmodified capsules. Analysis of X-ray image sequences and selected area spectra has been used to map the calcium gradient in capsules, to identify the presence of polyacrylate throughout the capsules and the localization of poly-N-vinylpyrrolidone in the outer regions of the Alginate capsules. The differences in the spatial distributions of these species have led to better understanding of the chemical...
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Deterioration of polyamino acid-coated Alginate Microcapsules in vivo.
Journal of biomaterials science. Polymer edition, 2002Co-Authors: J. M. Van Raamsdonk, R.m. Cornelius, John L. Brash, Patricia L. ChangAbstract:The implantation of immuno-isolated recombinant cell lines secreting a therapeutic protein in Alginate Microcapsules presents an alternative approach to gene therapy. Its clinical efficacy has recently been demonstrated in treating several genetic diseases in murine models. However, its application to humans will depend on the long-term structural stability of the Microcapsules. Based on previous implantations in canines, it appears that survival of Alginate–poly-L-lysine–Alginate Microcapsules in such large animals is short-lived. This article reports on the biological factors that may have contributed to the degradation of these Microcapsules after implantation in dogs. Alginate Microcapsules coated with poly-L-lysine or poly-L-arginine were implanted in subcutaneous or intraperitoneal sites. The retrieved Microcapsules showed a loss of mechanical stability, as measured by resistance to osmotic stress. The polyamino acid coats were rendered fragile and easily lost, particularly when poly-L-lysine was us...
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Development of small Alginate Microcapsules for recombinant gene product delivery to the rodent brain
Journal of biomaterials science. Polymer edition, 2002Co-Authors: Colin J.d. Ross, Patricia L. ChangAbstract:A novel form of gene therapy using encapsulated recombinant cells in Alginate Microcapsules has proven effective in treating several animal models of human diseases. For treating neurological deficits in rodents with this technology, the size of the Microcapsules has to be reduced for implantation in the central nervous system (CNS) to bypass the blood–brain barrier. This article reports the development of small Alginate Microcapsules suitable for implantation into the mouse CNS. By varying the encapsulation protocol, recombinant cells could be encapsulated in Microcapsules ranging in diameter from 5 to 2000 μm. The optimal size for implantation was determined to be 100–200 μm, based on the smallest, homogeneously sized, cell-filled Microcapsules that could pass the 500 μm inner diameter of a CNS-implantation needle. Compared with medium-sized (500–700 μm) Microcapsules, these small Microcapsules packed more tightly together with less inter-capsule space, resulting in an increased number of cells and a hi...
Kun Ho Yoon - One of the best experts on this subject based on the ideXlab platform.
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Suppression of Fibrotic Reactions of Chitosan-Alginate Microcapsules Containing Porcine Islets by Dexamethasone Surface Coating.
Endocrinology and metabolism (Seoul Korea), 2021Co-Authors: Min Jung Kim, Gilson Khang, Heon-seok Park, Ji-won Kim, Eun Young Lee, Marie Rhee, Young-hye You, Chung Gyu Park, Kun Ho YoonAbstract:BACKGROUND The microencapsulation is an ideal solution to overcome immune rejection without immunosuppressive treatment. Poor biocompatibility and small molecular antigens secreted from encapsulated islets induce fibrosis infiltration. Therefore, the aims of this study were to improve the biocompatibility of Microcapsules by dexamethasone coating and to verify its effect after xenogeneic transplantation in a streptozotocin-induced diabetes mice. METHODS Dexamethasone 21-phosphate (Dexa) was dissolved in 1% chitosan and was cross-linked with the Alginate microcapsule surface. Insulin secretion and viability assays were performed 14 days after microencapsulation. Dexa-containing chitosan-coated Alginate (Dexa-chitosan) or Alginate microencapsulated porcine islets were transplanted into diabetic mice. The fibrosis infiltration score was calculated from the harvested Microcapsules. The harvested Microcapsules were stained with trichrome and for insulin and macrophages. RESULTS No significant differences in glucose-stimulated insulin secretion and islet viability were noted among naked, Alginate, and Dexa-chitosan microencapsulated islets. After transplantation of microencapsulated porcine islets, nonfasting blood glucose were normalized in both the Dexa-chitosan and Alginate groups until 231 days. The average glucose after transplantation were lower in the Dexa-chitosan group than the Alginate group. Pericapsular fibrosis and inflammatory cell infiltration of Microcapsules were significantly reduced in Dexa-chitosan compared with Alginate Microcapsules. Dithizone and insulin were positive in Dexa-chitosan capsules. Although fibrosis and macrophage infiltration was noted on the surface, some Alginate Microcapsules were stained with insulin. CONCLUSION Dexa coating on Microcapsules significantly suppressed the fibrotic reaction on the capsule surface after transplantation of xenogenic islets containing Microcapsules without any harmful effects on the function and survival of the islets.
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Reduction of inflammatory reaction in the use of purified Alginate Microcapsules
Journal of biomaterials science. Polymer edition, 2012Co-Authors: A Ram Kim, Ji Hye Hwang, Kun Ho Yoon, Dongwon Lee, Hye Min Kim, Ha Neul Kim, Jeong Eun Song, Young Il Yang, Gilson KhangAbstract:Alginate, a polysaccharide extracted from brown seaweed, remains the most widely used biomaterial for immobilizing cells to be transplanted, because of the good viability of the encapsulated cells and the relatively ease of processing for cell encapsulation. However, the main drawback is the immune reaction in vivo. To overcome this problem, we have demonstrated a modified Korbutt method for Alginate purification. After Alginate Microcapsules were manufactured, NIH/3T3 fibroblast cells were seeded in purified and non-purified Alginate Microcapsules, and the cell proliferation was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. Reverse transcriptase-polymerase chain reaction was performed to assess the mRNA expression of RAW 264.7 macrophage cells for inflammation cytokines such as TNF-α. Purified and non-purified Alginate Microcapsules were implanted into Wister rats, and subsequently extracted after 1–2 weeks. Tissues surrounding the implants were harvested and underwent h...
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EFFECT OF PURIFIED Alginate Microcapsules ON THE REGENERATION OF CHONDROCYTES
Biomedical Engineering: Applications Basis and Communications, 2012Co-Authors: Ji Hye Hwang, On You Kim, A Ram Kim, Ji Yeon Bae, Su Mi Jeong, Jung Bo Shim, Kun Ho Yoon, Dongwon Lee, Gilson KhangAbstract:Adult articular cartilage tissue has poor capability of self-repair. Therefore, a variety of tissue engineering approaches are motivated by the clinical need for articular repair. Alginate has been used as a biomaterial for cartilage regeneration. The Alginate is a natural polymer that is extracted from seaweeds and purification. However, the main drawback is the immune rejection in vivo. To overcome this problem, we have developed the biocompability of Alginate using modified Korbutt method. After Alginate was purified, purified Alginate Microcapsules were used in cartilage regeneration. Chondrocytes were seeded in purified and nonpurified Alginate Microcapsules, and then cell viability, proliferation and phenotype were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted to confirm mRNA expression on collagen type I and collagen type II for chondrocytes phenotype. Hematoxylin and eosin (H&E) and Safranin-O histological staining showed tissue growth at the interface during the first 10 days. In this study, chondrocytes in purified Alginate Microcapsules had higher cell viability, proliferation and more phenotype expression than those in nonpurified Alginate Microcapsules. The results suggest that the purified Alginate microcapsule is useful for cartilage regeneration.
Liji Jin - One of the best experts on this subject based on the ideXlab platform.
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Chitosan–Alginate Microcapsules for Oral Delivery of Egg Yolk Immunoglobulin (IgY): Effects of Chitosan Concentration
Applied biochemistry and biotechnology, 2009Co-Authors: Liji Jin, Yuhong Zhen, Linhui WangAbstract:In our previous study, chitosan-Alginate Microcapsules were developed to protect egg yolk immunoglobulin (IgY) from gastric inactivation. The present study was undertaken to determine the effect of chitosan concentration (0-0.8%; w/v) on various properties of the Microcapsules in order to produce the optimum chitosan-Alginate Microcapsules for use in the oral delivery of IgY. The properties investigated included microcapsule morphology, loading capacity for IgY (expressed as the IgY loading percentage, w/w, of Microcapsules), encapsulation efficiency (EE%), in vitro gastroresistance, and IgY release. IgY loading percentage and EE% were both highest at 0.2% (w/v) chitosan, and, above this level, further increases were not observed. The stability of IgY in simulated gastric fluid (pH 1.2) was significantly improved by encapsulation in Alginate Microcapsules (IgY retained 43.5% of its activity) and was further improved by including chitosan at any of the chitosan concentrations assessed (IgY retained an average of 69.4% activity) although there was no difference in protection of gastric inactivation among concentrations of chitosan varying from 0.05% to 0.8% (w/v). Higher chitosan concentrations (i.e., >/=0.2%; w/v) prolonged the release of IgY from the Microcapsules during simulated intestinal fluid incubation (pH 6.8). However, above the 0.2% (w/v) level, no significant differences were observed. We conclude that the optimum chitosan concentration for microencapsulation is 0.2% (w/v).
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Chitosan-Alginate Microcapsules for oral delivery of egg yolk immunoglobulin (IgY): in vivo evaluation in a pig model of enteric colibacillosis.
Veterinary immunology and immunopathology, 2008Co-Authors: Liji Jin, Jude E Uzonna, Jun-jun Liu, Yuhong ZhenAbstract:In our previous study, the applicability of chitosan-Alginate Microcapsules for oral delivery of egg yolk immunoglobulin (IgY) was established in a simulated gastrointestinal tract environment. The objective of the present study was to evaluate the protective efficacy of microencapsulated IgY against K88+ ETEC (enterotoxigenic Escherichia coli)-induced diarrhea in 40-day-old pigs. Groups of pigs orally challenged with 10(11) cfu/mL of K88+ ETEC were fed with non-encapsulated IgY, microencapsulated IgY and aureomycin-treated feed respectively. The clinical response of each group was monitored and evaluated in terms of lethargy, inappetence, occurrence of diarrhea, fecal consistency score, weight loss and recovery rate. The results showed that treatment of infected pigs with microencapsulated IgY significantly (P
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Chitosan–Alginate Microcapsules for oral delivery of egg yolk immunoglobulin (IgY): In vivo evaluation in a pig model of enteric colibacillosis
Veterinary Immunology and Immunopathology, 2008Co-Authors: Liji Jin, Jude E Uzonna, Jun-jun Liu, Yuhong ZhenAbstract:In our previous study, the applicability of chitosan-Alginate Microcapsules for oral delivery of egg yolk immunoglobulin (IgY) was established in a simulated gastrointestinal tract environment. The objective of the present study was to evaluate the protective efficacy of microencapsulated IgY against K88+ ETEC (enterotoxigenic Escherichia coli)-induced diarrhea in 40-day-old pigs. Groups of pigs orally challenged with 10(11) cfu/mL of K88+ ETEC were fed with non-encapsulated IgY, microencapsulated IgY and aureomycin-treated feed respectively. The clinical response of each group was monitored and evaluated in terms of lethargy, inappetence, occurrence of diarrhea, fecal consistency score, weight loss and recovery rate. The results showed that treatment of infected pigs with microencapsulated IgY significantly (P
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chitosan Alginate Microcapsules for oral delivery of egg yolk immunoglobulin igy
Journal of Agricultural and Food Chemistry, 2007Co-Authors: Liji Jin, T A Mcallister, Kim Stanford, Yuhong Zhen, Yongxin SunAbstract:Chitosan-Alginate Microcapsules were evaluated as a method of oral delivery of IgY antibodies. Physical characteristics, encapsulation efficiency (EE%), the loading capacity for IgY (IgY loading percentage, %, w/w of Microcapsules), gastro-resistance, and release characteristics of these Microcapsules in vitro under varying pH were investigated. Optimum physical factors were established for preparation of homogeneous, spherical, and smooth Microcapsules. IgY loading% was not significantly altered by pH of the encapsulation medium. Encapsulation efficiency was highest (73.93%) at a pH of 3.5, above which EE% decreased significantly (p < 0.05). IgY was released from Microcapsules upon exposure to simulated intestinal fluid (SIF, pH 6.8), and decreasing pH increased significantly IgY release (p < 0.05). The stability of IgY in simulated gastric fluid (SGF, pH 1.2) was greatly improved by encapsulation in chitosan-Alginate Microcapsules, and the residual activity was not affected by pH of the encapsulation medium. Moreover, microencapsulated IgY was significantly resistant to pepsin hydrolysis. This approach may enable intact IgY to reach target microorganisms within the lower digestive tract.
Pei Lun Chang - One of the best experts on this subject based on the ideXlab platform.
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Osmotic pressure test: A simple, quantitative method to assess the mechanical stability of Alginate Microcapsules
Journal of Biomedical Materials Research, 2001Co-Authors: J. M. Van Raamsdonk, Pei Lun ChangAbstract:Implantation of microencapsulated, nonautologous cells and tissues is an effective method to deliver therapeutic proteins in vivo. Its success depends on the maintenance of the immunoisolating barrier provided by the microcapsule. Thus, one goal in the development of this technology is to create mechanically stable Microcapsules. We have developed an osmotic pressure test to quantify the strength of Microcapsules by exposing Alginate Microcapsules to a graded series of hypotonic solutions and quantifying the percentage of broken Microcapsules. The test was validated by confirming the relative strengths of different types of Alginate capsules, previously known from implantation in dogs to have differing mechanical stability in vivo. Thus, solid Alginate Microcapsules crosslinked with Ba(2+) were shown to be stronger than those crosslinked with Ca(2+), which in turn were shown to be stronger than the corresponding hollow Alginate Microcapsules. The incorporation of cells was demonstrated to reduce the mechanical stability of the Microcapsules significantly. Hence, this test provides a simple and quantitative method for rapidly determining the strength of a large number of Microcapsules. Thus, it is suitable for monitoring the mechanical stability of various types of Microcapsules, predicting the performance of Microcapsules in vivo, and for quality control of Microcapsules during scale-up productions.
Ruyun Lou - One of the best experts on this subject based on the ideXlab platform.
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fabrication of stable galactosylated Alginate Microcapsules via covalent coupling onto hydroxyl groups for hepatocytes applications
Carbohydrate Polymers, 2017Co-Authors: Ruyun Lou, Yizhe Song, Ying Ren, Huizhen Zheng, Xin Guo, Yunfei LinAbstract:Galactose moieties are covalently coupled with sodium Alginate to enhance liver-specific functions in Microcapsules owing to the specific interaction between the galactose moieties and the asialoglycoprotein receptors (ASGPRs) of hepatocytes. In this study, galactosylated Alginate (L-NH2-OH-Alginate) based Microcapsules with desirable stability and a suitable 3D microenvironment are designed and fabricated for primary hepatocyte applications. The designed L-NH2-OH-Alginate is fabricated via the application of ethylenediamine grafted lactobionic acid (L-NH2) onto the hydroxyl groups of sodium Alginate so that the negatively charged carboxyl groups intact in L-NH2-OH-Alginate can effectively bond with Ca2+ to form a stable three-dimensional gel network; a subsequent reaction with polycations forms a stable membrane of Microcapsules. As a result, L-NH2-OH-Alginate based Microcapsules exhibit an excellent mechanical stability. Moreover, with a higher degree of substitution in L-NH2-OH-Alginate (DS 0.41), the hepatocytes entrapped in L-NH2-OH-Alginate Microcapsules exhibit better viability and well-maintained liver-specific functions.
