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Alginate Microcapsules

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Patricia L. Chang – One of the best experts on this subject based on the ideXlab platform.

  • Biological properties of photocrosslinked Alginate Microcapsules
    Journal of biomedical materials research. Part B Applied biomaterials, 2005
    Co-Authors: Feng Shen, R.m. Cornelius, John L. Brash, Pasquale Cirone, Ronald F. Childs, Patricia L. Chang
    Abstract:

    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.

  • A novel method to enhance the stability of Alginate-poly-L-lysine-Alginate Microcapsules
    Journal of biomaterials science. Polymer edition, 2005
    Co-Authors: Maggie Sanju Wang, Ronald F. Childs, Patricia L. Chang
    Abstract:

    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…

  • Quantitative chemical mapping of sodium acrylate- and N-vinylpyrrolidone-enhanced Alginate Microcapsules.
    Journal of biomaterials science. Polymer edition, 2005
    Co-Authors: Tohru Araki, Patricia L. Chang, Feng Shen, Maggie Sanju Wang, Adam P. Hitchcock, Ronald F. Childs
    Abstract:

    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…

Kun Ho Yoon – One of the best experts on this subject based on the ideXlab platform.

Liji Jin – One of the best experts on this subject based on the ideXlab platform.

Pei Lun Chang – One of the best experts on this subject based on the ideXlab platform.

  • Osmotic pressure test: A simple, quantitative method to assess the mechanical stability of Alginate Microcapsules
    Journal of Biomedical Materials Research, 2001
    Co-Authors: J. M. Van Raamsdonk, Pei Lun Chang
    Abstract:

    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.