17 results on '"Arun, K."'
Search Results
2. Protein-free formation of bone-like apatite: New insights into the key role of carbonation
- Author
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Deymier, Alix C., Nair, Arun K., Depalle, Baptiste, Qin, Zhao, Arcot, Kashyap, Drouet, Christophe, Yoder, Claude H., Buehler, Markus J., Thomopoulos, Stavros, Genin, Guy M., and Pasteris, Jill D.
- Published
- 2017
- Full Text
- View/download PDF
3. The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers
- Author
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Bury, Matthew I., Fuller, Natalie J., Meisner, Jay W., Hofer, Matthias D., Webber, Matthew J., Chow, Lesley W., Prasad, Sheba, Thaker, Hatim, Yue, Xuan, Menon, Vani S., Diaz, Edward C., Stupp, Samuel I., Cheng, Earl Y., and Sharma, Arun K.
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- 2014
- Full Text
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4. Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors
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Ganesh, Shanthi, Iyer, Arun K., Morrissey, David V., and Amiji, Mansoor M.
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- 2013
- Full Text
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5. Tumor hypoxia directed multimodal nanotherapy for overcoming drug resistance in renal cell carcinoma and reprogramming macrophages
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Arun K. Iyer, Samaresh Sau, Rami Alzhrani, Arun K. Rishi, Ulka N. Vaishampayan, Lisa Polin, Hashem O. Alsaab, and Vino T. Cheriyan
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0301 basic medicine ,Sorafenib ,Programmed cell death ,Cell Survival ,Biophysics ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,Bioengineering ,Caspase 3 ,Proof of Concept Study ,Article ,Permeability ,Theranostic Nanomedicine ,Biomaterials ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Everolimus ,Carbonic Anhydrase IX ,Carcinoma, Renal Cell ,Drug Carriers ,Tumor hypoxia ,Chemistry ,Macrophages ,Cellular Reprogramming ,Combined Modality Therapy ,Cell Hypoxia ,Kidney Neoplasms ,Acetazolamide ,030104 developmental biology ,Cell killing ,Drug Resistance, Neoplasm ,Mechanics of Materials ,030220 oncology & carcinogenesis ,Ceramics and Composites ,Cancer research ,Nanoparticles ,Tumor Hypoxia ,Female ,medicine.drug - Abstract
Drug resistance is one of the significant clinical burden in renal cell carcinoma (RCC). The development of drug resistance is attributed to many factors, including impairment of apoptosis, elevation of carbonic anhydrase IX (CA IX, a marker of tumor hypoxia), and infiltration of tumorigenic immune cells. To alleviate the drug resistance, we have used Sorafenib (Sor) in combination with tumor hypoxia directed nanoparticle (NP) loaded with a new class of apoptosis inducer, CFM 4.16 (C4.16), namely CA IX-C4.16. The NP is designed to selectively deliver the payload to the hypoxic tumor (core), provoke superior cell death in parental (WT) and Everolimus-resistant (Evr-res) RCC and selectively downmodulate tumorigenic M2-macrophage. Copper-free ‘ click ’ chemistry was utilized for conjugating SMA-TPGS with Acetazolamide (ATZ, a CA IX-specific targeting ligand). The NP was further tagged with a clinically approved NIR dye (S0456) for evaluating hypoxic tumor core penetration and organ distribution. Imaging of tumor spheroid treated with NIR dye-labeled CA IX-SMA-TPGS revealed remarkable tumor core penetration that was modulated by CA IX-mediated targeting in hypoxic-A498 RCC cells. The significant cell killing effect with synergistic combination index (CI) of CA IX-C4.16 and Sor treatment suggests efficient reversal of Evr-resistance in A498 cells. The CA IX directed nanoplatform in combination with Sor has shown multiple benefits in overcoming drug resistance through (i) inhibition of p -AKT, (ii) upregulation of tumoricidal M1 macrophages resulting in induction of caspase 3/7 mediated apoptosis of Evr-res A498 cells in macrophage-RCC co-culturing condition, (iii) significant in vitro and in vivo Evr-res A498 tumor growth inhibition as compared to individual therapy, and (iv) untraceable liver and kidney toxicity in mice. Near-infrared (NIR) imaging of CA IX-SMA-TPGS-S0456 in Evr-res A498 RCC model exhibited significant accumulation of CA IX-oligomer in tumor core with >3-fold higher tumor uptake as compared to control. In conclusion, this proof-of-concept study demonstrates versatile tumor hypoxia directed nanoplatform that can work in synergy with existing drugs for reversing drug-resistance in RCC accompanied with re-education of tumor-associated macrophages, that could be applied universally for several hypoxic tumors.
- Published
- 2018
6. The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma
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Iyer, Arun K., Su, Yang, Feng, Jinjin, Lan, Xiaoli, Zhu, Xiaodong, Liu, Yue, Gao, Dongwei, Seo, Youngho, VanBrocklin, Henry F., Courtney Broaddus, V., Liu, Bin, and He, Jiang
- Published
- 2011
- Full Text
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7. A bioactive self-assembled membrane to promote angiogenesis
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Chow, Lesley W., Bitton, Ronit, Webber, Matthew J., Carvajal, Daniel, Shull, Kenneth R., Sharma, Arun K., and Stupp, Samuel I.
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- 2011
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8. Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films
- Author
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Sharma, Arun K., Hota, Partha V., Matoka, Derek J., Fuller, Natalie J., Jandali, Danny, Thaker, Hatim, Ameer, Guillermo A., and Cheng, Earl Y.
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- 2010
- Full Text
- View/download PDF
9. Co-assembling peptides as defined matrices for endothelial cells
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Jung, Jangwook P., Nagaraj, Arun K., Fox, Emily K., Rudra, Jai S., Devgun, Jason M., and Collier, Joel H.
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- 2009
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10. High-loading nanosized micelles of copoly(styrene–maleic acid)–zinc protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor
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Iyer, Arun K., Greish, Khaled, Fang, Jun, Murakami, Ryoichi, and Maeda, Hiroshi
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- 2007
- Full Text
- View/download PDF
11. Protein-free formation of bone-like apatite: New insights into the key role of carbonation
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Markus J. Buehler, Baptiste Depalle, Stavros Thomopoulos, Jill D. Pasteris, Claude H. Yoder, Christophe Drouet, Guy M. Genin, Zhao Qin, Arun K. Nair, Alix C. Deymier, Kashyap Arcot, Centre National de la Recherche Scientifique - CNRS (FRANCE), Columbia University (USA), Franklin and Marshall College (USA), Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE), Massachusetts Institute of Technology - MIT (USA), University of Arkansas (USA), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Washington University in St. Louis (USA), Imperial College London (UNITED KINGDOM), Lancaster University (UNITED KINGDOM), Centre Interuniversitaire de Recherche et d'Ingénierie des Matériaux - CIRIMAT (Toulouse, France), Columbia University [New York], University of Arkansas [Fayetteville], Imperial College London, Massachusetts Institute of Technology (MIT), University of Washington [Seattle], Centre interuniversitaire de recherche et d'ingenierie des matériaux (CIRIMAT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Franklin and Marshall College, and Institut National Polytechnique de Toulouse - INPT (FRANCE)
- Subjects
Biomineralization ,Materials science ,Carbonate ,Surface Properties ,Matériaux ,Inorganic chemistry ,Biophysics ,Carbonates ,Bioengineering ,02 engineering and technology ,010402 general chemistry ,Spectrum Analysis, Raman ,01 natural sciences ,Apatite ,Bone and Bones ,Article ,[SPI.MAT]Engineering Sciences [physics]/Materials ,Biomaterials ,Molecular dynamics ,chemistry.chemical_compound ,Lattice constant ,X-Ray Diffraction ,Apatites ,Elastic Modulus ,Spectroscopy, Fourier Transform Infrared ,Solubility ,Bone ,Proteins ,[CHIM.MATE]Chemical Sciences/Material chemistry ,021001 nanoscience & nanotechnology ,Surface energy ,0104 chemical sciences ,Chemical engineering ,chemistry ,Calcium phosphate ,Mechanics of Materials ,visual_art ,Ceramics and Composites ,visual_art.visual_art_medium ,Thermodynamics ,Crystallite ,Powders ,0210 nano-technology ,Crystallization ,Substitution - Abstract
International audience; The nanometer-sized plate-like morphology of bone mineral is necessary for proper bone mechanics and physiology. However, mechanisms regulating the morphology of these mineral nanocrystals remain unclear. The dominant hypothesis attributes the size and shape regulation to organic-mineral interactions. Here, we present data supporting the hypothesis that physicochemical effects of carbonate integration within the apatite lattice control the morphology, size, and mechanics of bioapatite mineral crystals. Carbonated apatites synthesized in the absence of organic molecules presented plate-like morphologies and nanoscale crystallite dimensions. Experimentally-determined crystallite size, lattice spacing, solubility and atomic order were modified by carbonate concentration. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations predicted changes in surface energy and elastic moduli with carbonate concentration. Combining these results with a scaling law predicted the experimentally observed scaling of size and energetics with carbonate concentration. The experiments and models describe a clear mechanism by which crystal dimensions are controlled by carbonate substitution. Furthermore, the results demonstrate that carbonate substitution is sufficient to drive the formation of bone-like crystallites. This new understanding points to pathways for biomimetic synthesis of novel, nanostructured biomaterials.
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- 2016
12. Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors
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Arun K. Iyer, David V. Morrissey, Mansoor M. Amiji, and Shanthi Ganesh
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Small interfering RNA ,Biophysics ,Cell Cycle Proteins ,Bioengineering ,Protein Serine-Threonine Kinases ,Article ,Biomaterials ,Mice ,RNA interference ,Cell Line, Tumor ,Neoplasms ,Proto-Oncogene Proteins ,Gene Knockdown Techniques ,Animals ,Humans ,Polyethyleneimine ,Gene silencing ,Gene Silencing ,Hyaluronic Acid ,Neoplasm Metastasis ,RNA, Small Interfering ,Gene knockdown ,biology ,CD44 ,Gene Transfer Techniques ,Transfection ,Xenograft Model Antitumor Assays ,Endocytosis ,Disease Models, Animal ,Hyaluronan Receptors ,Mechanics of Materials ,Cancer cell ,Ceramics and Composites ,Cancer research ,biology.protein ,Nanoparticles - Abstract
Anticancer therapeutics employing RNA interference mechanism holds promising potentials for sequence-specific silencing of target genes. However targeted delivery of siRNAs to tumor tissues and cells and more importantly, their intracellular release at sites of interest still remains a major challenge that needs to be addressed before this technique could become a clinically viable option. In the current study, we have engineered and screened a series of CD44 targeting hyaluronic acid (HA) based self-assembling nanosystems for targeted siRNA delivery. The HA polymer was functionalized with lipids of varying carbon chain lengths/nitrogen content, as well as polyamines for assessing siRNA encapsulation. From the screens, several HA-derivatives were identified that could stably encapsulate/complex siRNAs and form self-assembled nanosystems, as determined by gel retardation assays and dynamic light scattering. Many HA derivatives could transfect siRNAs into cancer cells overexpressing CD44 receptors. Interestingly, blocking the CD44 receptors on the cells using free excess soluble HA prior to incubation of cy3-labeled-siRNA loaded HA nano-assemblies resulted in >90% inhibition of the receptor mediated uptake, confirming target specificity. In addition, SSB/PLK1 siRNA encapsulated in HA-PEI/PEG nanosystems demonstrated dose dependent and target specific gene knockdown in both sensitive and resistant A549 lung cancer cells overexpressing CD44 receptors. More importantly, these siRNA encapsulated nanosystems demonstrated tumor selective uptake and target specific gene knock down in vivo in solid tumors as well as in metastatic tumors. The HA based nanosystems thus portend to be promising siRNA delivery vectors for systemic targeting of CD44 overexpressing cancers including tumor initiating (stem-) cells and metastatic lesions.
- Published
- 2013
13. A bioactive self-assembled membrane to promote angiogenesis
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Lesley W. Chow, Arun K. Sharma, Ronit Bitton, Samuel I. Stupp, Daniel Carvajal, Kenneth R. Shull, and Matthew J. Webber
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Vascular Endothelial Growth Factor A ,Cell Survival ,Angiogenesis ,Basic fibroblast growth factor ,Biophysics ,Neovascularization, Physiologic ,Biocompatible Materials ,Bioengineering ,Chick Embryo ,Biology ,Article ,Chorioallantoic Membrane ,Biomaterials ,chemistry.chemical_compound ,Hyaluronic acid ,Animals ,Humans ,Hyaluronic Acid ,Cells, Cultured ,Microscopy, Confocal ,Membrane structure ,Mesenchymal Stem Cells ,Cell biology ,Vascular endothelial growth factor ,Vascular endothelial growth factor A ,Chorioallantoic membrane ,Membrane ,chemistry ,Mechanics of Materials ,Microscopy, Electron, Scanning ,Ceramics and Composites ,Fibroblast Growth Factor 2 ,Chickens - Abstract
We report here on the formation of a bioactive hierarchically structured membrane by self-assembly. The membrane is formed with hyaluronic acid and peptide amphiphiles with binding affinity for heparin, and its hierarchical structure contains both an amorphous zone and a layer of fibrils oriented perpendicular to the membrane plane. The design of bioactivity is based on the potential ability to bind and slowly release heparin-binding growth factors. Human mesenchymal stem cells seeded on these membranes attached and remained viable. Basic fibroblast growth factor (FGF2) and vascular endothelial growth factor (VEGF) were incorporated within the membrane structure prior to self-assembly and released into media over a prolonged period of time (14 days). Using the chicken chorioallantoic membrane (CAM) assay, we also found that these membranes induced a significant and rapid enhancement of angiogenesis relative to controls.
- Published
- 2011
14. Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1,8-octanediol-co-citrate) based thin films
- Author
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Natalie J. Fuller, Earl Y. Cheng, Guillermo A. Ameer, Danny Jandali, Hatim Thaker, Arun K. Sharma, Derek J. Matoka, and Partha V. Hota
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Pathology ,medicine.medical_specialty ,Materials science ,Cell Survival ,Polymers ,Urinary Bladder ,Calponin ,Biophysics ,Fluorescent Antibody Technique ,Bone Marrow Cells ,Bioengineering ,Citric Acid ,Biomaterials ,Rats, Nude ,Methyl Green ,Trichrome ,Elastic Modulus ,medicine ,Animals ,Humans ,Regeneration ,Citrates ,Urinary bladder ,Staining and Labeling ,Tissue Scaffolds ,biology ,Regeneration (biology) ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Muscle, Smooth ,Rats ,Caldesmon ,medicine.anatomical_structure ,Elastomers ,Mechanics of Materials ,Ceramics and Composites ,biology.protein ,Eosine Yellowish-(YS) ,Female ,Collagen ,Bone marrow ,Azo Compounds ,Elastin ,Biomedical engineering - Abstract
Bladder regeneration studies have yielded inconclusive results possibly due to the use of unfavorable cells and primitive scaffold design. We hypothesized that human mesenchymal stem cells seeded onto poly(1,8-octanediol-co-citrate) elastomeric thin films would provide a suitable milieu for partial bladder regeneration. POCfs were created by reacting citric acid with 1,8-octanediol and seeded on opposing faces with human MSCs and urothelial cells; normal bladder smooth muscle cells and UCs, or unseeded POCfs. Partial cystectomized nude rats were augmented with the aforementioned POCfs, enveloped with omentum and sacrificed at 4 and 10 weeks. Isolated bladders were subjected to Trichrome and anti-human gamma-tubulin, calponin, caldesmon, smooth muscle gamma-actin, and elastin stainings. Mechanical testing of POCfs revealed a Young's modulus of 138 kPa with elongation 137% its initial length without permanent deformation demonstrating its high uniaxial elastic potential. Trichrome and immunofluorescent staining of MSC/UC POCf augmented bladders exhibited typical bladder architecture with muscle bundle formation and the expression and retention of bladder smooth muscle contractile proteins of human derivation. Quantitative morphometry of MSC/UC samples revealed muscle/collagen ratios approximately 1.75x greater than SMC/UC controls at 10 weeks. Data demonstrate MSC seeded POCfs support partial regeneration of bladder tissue in vivo.
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- 2010
15. Co-assembling peptides as defined matrices for endothelial cells
- Author
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Joel H. Collier, Jai S. Rudra, Jason M. Devgun, Arun K. Nagaraj, Emily K. Fox, and Jangwook P. Jung
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Materials science ,Biophysics ,Bioengineering ,Peptide ,Ligands ,Fibril ,Regenerative medicine ,Article ,Biomaterials ,Mice ,Microscopy, Electron, Transmission ,In vivo ,Cell Adhesion ,Animals ,Humans ,Cell adhesion ,Cells, Cultured ,chemistry.chemical_classification ,Viscosity ,Circular Dichroism ,Endothelial Cells ,Elasticity ,In vitro ,Mice, Inbred C57BL ,chemistry ,Mechanics of Materials ,Cell culture ,Self-healing hydrogels ,Ceramics and Composites ,Gelatin ,Female ,Peptides ,Biomedical engineering - Abstract
Self-assembling peptides and peptide derivatives bearing cell-binding ligands are increasingly being investigated as defined cell culture matrices and as scaffolds for regenerative medicine. In order to systematically refine such scaffolds to elicit specific desired cell behaviors, ligand display should ideally be achieved without inadvertently altering other physicochemical properties such as viscoelasticity. Moreover, for in vivo applications, self-assembled biomaterials must exhibit low immunogenicity. In the present study, multi-peptide co-assembling hydrogels based on the beta-sheet fibrillizing peptide Q11 (QQKFQFQFEQQ) were designed such that they presented RGDS or IKVAV ligands on their fibril surfaces. In co-assemblies of the ligand-bearing peptides with Q11, ligand incorporation levels capable of influencing the attachment, spreading, morphology, and growth of human umbilical vein endothelial cells (HUVECs) did not significantly alter the materials’ fibrillization, beta-turn secondary structure, or stiffness. RGDS-Q11 specifically increased HUVEC attachment, spreading, and growth when co-assembled into Q11 gels, whereas IKVAV-Q11 exerted a more subtle influence on attachment and morphology. Additionally, Q11 and RGDS-Q11 were minimally immunogenic in mice, making Q11-based biomaterials attractive candidates for further investigation as defined, modular extracellular matrices for applications in vitro and in vivo.
- Published
- 2009
16. The promotion of functional urinary bladder regeneration using anti-inflammatory nanofibers
- Author
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Vani S. Menon, Lesley W. Chow, Arun K. Sharma, Matthias D. Hofer, Hatim Thaker, Edward C. Diaz, Natalie J. Fuller, Xuan Yue, Sheba Prasad, Matthew I. Bury, Matthew J. Webber, Earl Y. Cheng, Samuel I. Stupp, and Jay W. Meisner
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Neutrophils ,medicine.medical_treatment ,Urinary Bladder ,Biophysics ,Anti-Inflammatory Agents ,Nanofibers ,Bioengineering ,Inflammation ,Article ,Biomaterials ,Rats, Nude ,Intestine, Small ,medicine ,Macrophage ,Animals ,Regeneration ,Intestinal Mucosa ,Decellularization ,Urinary bladder ,Innate immune system ,Tissue Scaffolds ,business.industry ,Regeneration (biology) ,Macrophages ,Immunity, Innate ,Rats ,Cytokine ,medicine.anatomical_structure ,Mechanics of Materials ,Immunology ,Ceramics and Composites ,Cancer research ,Female ,medicine.symptom ,Wound healing ,business - Abstract
Current attempts at tissue regeneration utilizing synthetic and decellularized biologic-based materials have typically been met in part by innate immune responses in the form of a robust inflammatory reaction at the site of implantation or grafting. This can ultimately lead to tissue fibrosis with direct negative impact on tissue growth, development, and function. In order to temper the innate inflammatory response, anti-inflammatory signals were incorporated through display on self-assembling peptide nanofibers to promote tissue healing and subsequent graft compliance throughout the regenerative process. Utilizing an established urinary bladder augmentation model, the highly pro-inflammatory biologic scaffold (decellularized small intestinal submucosa) was treated with anti-inflammatory peptide amphiphiles (AIF-PAs) or control peptide amphiphiles and used for augmentation. Significant regenerative advantages of the AIF-PAs were observed including potent angiogenic responses, limited tissue collagen accumulation, and the modulation of macrophage and neutrophil responses in regenerated bladder tissue. Upon further characterization, a reduction in the levels of M2 macrophages was observed, but not in M1 macrophages in control groups, while treatment groups exhibited decreased levels of M1 macrophages and stabilized levels of M2 macrophages. Pro-inflammatory cytokine production was decreased while anti-inflammatory cytokines were up-regulated in treatment groups. This resulted in far fewer incidences of tissue granuloma and bladder stone formation. Finally, functional urinary bladder testing revealed greater bladder compliance and similar capacities in groups treated with AIF-PAs. Data demonstrate that AIF-PAs can alleviate galvanic innate immune responses and provide a highly conducive regenerative milieu that may be applicable in a variety of clinical settings.
- Published
- 2014
17. High-loading nanosized micelles of copoly(styrene-maleic acid)-zinc protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor
- Author
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Ryoichi Murakami, Hiroshi Maeda, Jun Fang, Arun K. Iyer, and Khaled Greish
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Materials science ,Maleic acid ,Metalloporphyrins ,Biophysics ,Protoporphyrins ,Bioengineering ,Biocompatible Materials ,Micelle ,Biomaterials ,Diffusion ,chemistry.chemical_compound ,Drug Delivery Systems ,Drug Stability ,Amphiphile ,Materials Testing ,Copolymer ,Organic chemistry ,Particle Size ,Micelles ,Aqueous solution ,Zinc protoporphyrin ,Maleates ,Nanostructures ,Heme oxygenase ,chemistry ,Mechanics of Materials ,Heme Oxygenase (Decyclizing) ,Ceramics and Composites ,Polystyrenes ,Protoporphyrin ,Nuclear chemistry - Abstract
Amphiphilic styrene–maleic acid (SMA) copolymer efficiently formed micelles with a potent heme oxygenase inhibitor–zinc protoporphyrin (ZnPP). The micelles were constructed by subtle pH adjustments to form non-covalent interaction between the hydrophobic ZnPP and amphiphilic SMA. The micelles (SMA–ZnPP) thus formed were nanoparticles with narrow size distribution in water (mean diameter 176.5 nm), having tunable loading (from 15% to 60% w/w of ZnPP) with remarkable aqueous solubility. SMA–ZnPP had an average molecular size of 144 kDa as determined by size-exclusion chromatography (SEC), this size is a marked increase from the molecular weight of free ZnPP (626.03 Da), suggesting the formation of micellar structure. The micelles showed a constant ZnPP release rate of about 0.5%/day in vitro at neutral pH. SMA–ZnPP micelles inhibited splenic microsomal HO-1 activity, in a competitive and dose-dependent manner, with an apparent inhibitory constant (Ki) of 0.12 μ m , comparable to free ZnPP and also exhibited marked cytotoxic effect on KYSE-510 human esophageal cancer cells. The unique features of SMA–ZnPP micelles are that they are nanoparticles in aqueous solution having high water solubility and loading, yet macromolecular in nature, which can be beneficial in targeted release of a potent HO-1 inhibitor.
- Published
- 2006
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