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Synthesis and characterization of biocompatible polyurethanes for controlled release of hydrophobic and hydrophilic drugs

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Frontiers of Chemical Science and Engineering 2014年第4期8卷 498-510页

作者： Juichen YANG Hong CHEN Yuan YUAN debanjan sarkar Jie ZHENG Department of Chemical and Biomolecular Engineering The University of Akron Akron OH 44325 USA Department of Biomedical Engineering University at Buffalol State University of New York Buffalo NY 14260 USA Department of Chemical and Biological Engineering University at Buffalo State University of New York Buffalo NY 14260 USA

Design of biocompatible and biodegradable polymer systems for sustained and controlled release of bioactive agents is critical for numerous biomedical applications. Here, we designed, synthesized, and char- acterized four polyurethane carrier systems for controlled release of model drugs. These polyurethanes are biocom- patible and biodegradable because they consist of biocompatible poly（ethylene glycol） or poly（caprolactone diol） as soft segment, linear aliphatic hexamethylene diisocyanate or symmetrical aliphatic cyclic dicyclohex- ylmethane-4,4＇-diisocyanate as hard segment, and biode- gradable urethane linkage. They were characterized with Fourier transform infrared spectroscopy, atomic force microscope, and differential scanning calorimetry, whereas their degradation behaviors were investigated in both phosphate buffered saline and enzymatic solutions. By tuning polyurethane segments, different release profiles of hydrophobic and hydrophilic drugs were obtained in the absence and presence of enzymes. Such difference in release profiles was attributed to a complex interplay among structure, hydrophobicity, and degradability of polyurethanes, the size and hydrophobicity of drugs, and drug-polymer interactions. Different drug-polyurethane combinations modulated the distribution and location of the drugs in polymer matrix, thus inducing different drug release mechanisms. Our results highlight an important role of segmental structure of the polyurethane as an engineering tool to control drug release.

关键词： polyurethanes controlled release drug delivery phase structure degradation

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Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of col agen-induced arthritis

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Bone Research 2014年第4期2卷 241-251页

作者： Xue Yuan Lee Ann Garrett-Sinha debanjan sarkar Shuying Yang Department of Oral Biology School of Dental MedicineUniversity at BuffaloThe State University of New YorkBuffaloNY 14214USA Department of Biochemistry School of Medicine and Biomedical SciencesUniversity at BuffaloThe State University of New YorkBuffaloNY 14203USA Laboratory for Biomaterials and Regenerative Therapeutics Department of Biomedical EngineeringUniversity at BuffaloThe State University of New YorkBuffaloNY 14260-2050USA Developmental Genomics Group New York State Center of Excellence in Bioinformatics and Life SciencesUniversity at BuffaloThe State University of New YorkBuffaloNY 14203USA

IFT20 is the smallest member of the intraflagellar transport protein（IFT） complex B. It is involved in cilia formation. Studies of IFT20 have been confined to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro. However, how IFT20 regulates T-cell development and activation in vivo is still unknown. We deleted the IFT20 gene in early and later stages of T-cell development by crossing IFT20flox/flox（IFT20f/f） mice with Lck-Cre and CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation and in the development of T cell-mediated collagen-induced arthritis（CIA）. We found that both Lck-Cre/IFT20f/f and CD4-Cre/IFT20f/f mice were indistinguishable from their wild-type littermates in body size, as well as in the morphology and weight of the spleen and thymus. However, the number of CD4- and CD8-positive cells was significantly lower in thymus and spleen in Lck-Cre/IFT20f/f mice. Meanwhile, the incidence and severity of CIA symptoms were significantly decreased, and inflammation in the paw was significantly inhibited in Lck-Cre/IFT20f/f mice compared to Lck-Cre/IFT201/1littermates. Deletion IFT20 in more mature T cells of CD4-Cre/IFT20f/f mice had only mild effects on the development of T cells and CIA. The expression of IL-1b, IL-6 and TGF-b1 were significantly downregulated in the paw of Lck-Cre/IFT20f/f mice, but just slight decreased in CD4-Cre/IFT20f/f mice. These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

关键词： T cells transgenic mice body size in vitro

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