The Experts below are selected from a list of 6090 Experts worldwide ranked by ideXlab platform
Eric W Howard - One of the best experts on this subject based on the ideXlab platform.
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whole animal knockout of smooth muscle alpha actin does not alter Excisional Wound healing or the fibroblast to myofibroblast transition
Wound Repair and Regeneration, 2013Co-Authors: James J Tomasek, Robert J Schwartz, Carol J Haaksma, Eric W HowardAbstract:The contractile phenotype and function of myofibroblasts have been proposed to play a critical role in Wound closure. It has been hypothesized smooth muscle alpha-actin expressed in myofibroblasts is critical for their formation and function. We have used smooth muscle α-actin-null mice to test this hypothesis. Full-thickness Excisional Wounds closed at a similar rate in smooth muscle α-actin -null and wild type mice. In addition, fibroblasts in smooth muscle α-actin-null granulation tissue when immunostained with a monoclonal antibody that recognizes all muscle actin isoforms exhibited a myofibroblast-like distribution and a stress fiber-like pattern, demonstrating that these cells acquired the myofibroblast phenotype. Dermal fibroblasts from smooth muscle α-actin-null and wild type mice formed stress fibers and supermature focal adhesions, and generated similar amounts of contractile force in response to transforming growth factor-β1. Smooth muscle γ-actin and skeletal muscle alpha-actin were expressed in smooth muscle α-actin-null myofibroblasts, as demonstrated by immunostaining, real-time PCR, and mass spectrometry. These results demonstrate that smooth muscle α-actin is not necessary for myofibroblast formation and function and for Wound closure, and that smooth muscle γ-actin and skeletal muscle α-actin may be able to functionally compensate for the lack of smooth muscle α-actin in myofibroblasts.
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whole animal knockout of smooth muscle alpha actin does not alter Excisional Wound healing or the fibroblast to myofibroblast transition
Wound Repair and Regeneration, 2013Co-Authors: James J Tomasek, Robert J Schwartz, Carol J Haaksma, Eric W HowardAbstract:The contractile phenotype and function of myofibroblasts have been proposed to play a critical role in Wound closure. It has been hypothesized that smooth muscle α-actin expressed in myofibroblasts is critical for its formation and function. We have used smooth muscle α-actin-null mice to test this hypothesis. Full-thickness Excisional Wounds closed at a similar rate in smooth muscle α-actin-null and wild-type mice. In addition, fibroblasts in smooth muscle α-actin-null granulation tissue when immunostained with a monoclonal antibody that recognizes all muscle actin isoforms exhibited a myofibroblast-like distribution and a stress fiber-like pattern, showing that these cells acquired the myofibroblast phenotype. Dermal fibroblasts from smooth muscle α-actin-null and wild-type mice formed stress fibers and supermature focal adhesions, and generated similar amounts of contractile force in response to transforming growth factor-β1. Smooth muscle γ-actin and skeletal muscle α-actin were expressed in smooth muscle α-actin-null myofibroblasts, as shown by immunostaining, real-time polymerase chain reaction, and mass spectrometry. These results show that smooth muscle α-actin is not necessary for myofibroblast formation and function and for Wound closure, and that smooth muscle γ-actin and skeletal muscle α-actin may be able to functionally compensate for the lack of smooth muscle α-actin in myofibroblasts.
Venkata Vamsi Krishna Venuganti - One of the best experts on this subject based on the ideXlab platform.
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layer by layer thin films for co delivery of tgf β sirna and epidermal growth factor to improve Excisional Wound healing
Aaps Pharmscitech, 2017Co-Authors: Praveen Kumar Mandapalli, Suman Labala, Anup Jose, Shubhmita Bhatnagar, Renuka Janupally, Dharmarajan Sriram, Venkata Vamsi Krishna VenugantiAbstract:The major challenge with treatment of dermal Wounds is accelerating healing process, while preventing the scar formation. Herein, we have fabricated layer-by-layer (LbL) polyelectrolyte multilayer films containing epidermal growth factor (EGF) and TGF-β siRNA to improve Excisional Wound healing and decrease scar formation. The chitosan and sodium alginate LbL thin films showed 13.0 MPa tensile strength and 2.22 N/cm2 skin adhesion strength. The LbL thin films were found to be cytocompatible, where A431 epidermal keratinocytes adhered to the film and showed 86.2 ± 0.8% cell growth compared with cells cultured in the absence of LbL thin film. In contrast, LbL thin film did not promote the Escherichia coli and Staphylococcus aureus bacterial colony formation. In a C57BL/6 mouse Excisional Wound model, application of LbL thin films containing TGF-β siRNA significantly (p < 0.05) reduced the TGF-β protein expression and collagen production. The LbL thin films containing EGF showed improved Wound contraction (<9 days post excision). The co-delivery of TGF-β siRNA and EGF using LbL thin films resulted in accelerated Wound healing and decreased collagen deposition. Furthermore, the LbL thin films with TGF-β siRNA and EGF combination showed greater reepithelialization. Taken together, we have successfully demonstrated the co-delivery of TGF-β siRNA and EGF peptide using LbL thin films to promote Wound healing and decrease scar formation.
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Layer-by-Layer Thin Films for Co-Delivery of TGF-β siRNA and Epidermal Growth Factor to Improve Excisional Wound Healing.
AAPS PharmSciTech, 2016Co-Authors: Praveen Kumar Mandapalli, Suman Labala, Anup Jose, Shubhmita Bhatnagar, Renuka Janupally, Dharmarajan Sriram, Venkata Vamsi Krishna VenugantiAbstract:The major challenge with treatment of dermal Wounds is accelerating healing process, while preventing the scar formation. Herein, we have fabricated layer-by-layer (LbL) polyelectrolyte multilayer films containing epidermal growth factor (EGF) and TGF-β siRNA to improve Excisional Wound healing and decrease scar formation. The chitosan and sodium alginate LbL thin films showed 13.0 MPa tensile strength and 2.22 N/cm2 skin adhesion strength. The LbL thin films were found to be cytocompatible, where A431 epidermal keratinocytes adhered to the film and showed 86.2 ± 0.8% cell growth compared with cells cultured in the absence of LbL thin film. In contrast, LbL thin film did not promote the Escherichia coli and Staphylococcus aureus bacterial colony formation. In a C57BL/6 mouse Excisional Wound model, application of LbL thin films containing TGF-β siRNA significantly (p
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effect of pirfenidone delivered using layer by layer thin film on Excisional Wound healing
European Journal of Pharmaceutical Sciences, 2016Co-Authors: Praveen Kumar Mandapalli, Jagadeesh Bojja, Suman Labala, Venkata Vamsi Krishna VenugantiAbstract:The aim of this study was to evaluate the effect of a new anti-fibrotic agent, pirfenidone (PFD), delivered using polyelectrolyte multilayer films on Excisional Wound healing. Polyelectrolyte multilayer films were prepared by layer-by-layer (LbL) sequential adsorption of chitosan and sodium alginate. The UV-spectrophotometer, FTIR and differential scanning calorimeter were used to characterize the LbL thin films. The PFD was entrapped within the LbL thin films and its effect on Excisional Wound healing was studied in C57BL/6. The total protein, collagen content and TGF-β expression within the Wound tissue were determined after application of PFD using LbL thin films, chitosan hydrogel and polyethylene glycol hydrogel. UV-spectrophotometer and FTIR studies showed a sequential adsorption of chitosan and alginate polymer layers to form LbL thin films. The thickness of LbL thin films with 15 bilayers was found to be 15 ± 2 μm. HPLC analysis showed a PFD loading efficiency of 1.0 ± 0.1mg in 1cm(2) area of LbL thin film. In vivo Wound healing studies in C57BL/6 mice showed an accelerated (<9 days) Wound contraction after treatment with the PFD compared with blank LbL thin film and commercial povidone-iodine gel (12 days). The collagen content within the Wound tissue was significantly (p<0.05) less after treatment with PFD compared with blank film application. Western blot analysis showed gradual decrease in TGF-β expression within the Wound tissue after treatment with PFD. This study for the first time demonstrated that new anti-fibrotic agent PFD loaded in LbL thin films can be utilized for Excisional Wound healing.
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Effect of pirfenidone delivered using layer-by-layer thin film on Excisional Wound healing
European Journal of Pharmaceutical Sciences, 2016Co-Authors: Praveen Kumar Mandapalli, Jagadeesh Bojja, Suman Labala, Venkata Vamsi Krishna VenugantiAbstract:The aim of this study was to evaluate the effect of a new anti-fibrotic agent, pirfenidone (PFD), delivered using polyelectrolyte multilayer films on Excisional Wound healing. Polyelectrolyte multilayer films were prepared by layer-by-layer (LbL) sequential adsorption of chitosan and sodium alginate. The UV-spectrophotometer, FTIR and differential scanning calorimeter were used to characterize the LbL thin films. The PFD was entrapped within the LbL thin films and its effect on Excisional Wound healing was studied in C57BL/6. The total protein, collagen content and TGF-β expression within the Wound tissue were determined after application of PFD using LbL thin films, chitosan hydrogel and polyethylene glycol hydrogel. UV-spectrophotometer and FTIR studies showed a sequential adsorption of chitosan and alginate polymer layers to form LbL thin films. The thickness of LbL thin films with 15 bilayers was found to be 15 ± 2 μm. HPLC analysis showed a PFD loading efficiency of 1.0 ± 0.1 mg in 1 cm2area of LbL thin film. In vivo Wound healing studies in C57BL/6 mice showed an accelerated (
James J Tomasek - One of the best experts on this subject based on the ideXlab platform.
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whole animal knockout of smooth muscle alpha actin does not alter Excisional Wound healing or the fibroblast to myofibroblast transition
Wound Repair and Regeneration, 2013Co-Authors: James J Tomasek, Robert J Schwartz, Carol J Haaksma, Eric W HowardAbstract:The contractile phenotype and function of myofibroblasts have been proposed to play a critical role in Wound closure. It has been hypothesized smooth muscle alpha-actin expressed in myofibroblasts is critical for their formation and function. We have used smooth muscle α-actin-null mice to test this hypothesis. Full-thickness Excisional Wounds closed at a similar rate in smooth muscle α-actin -null and wild type mice. In addition, fibroblasts in smooth muscle α-actin-null granulation tissue when immunostained with a monoclonal antibody that recognizes all muscle actin isoforms exhibited a myofibroblast-like distribution and a stress fiber-like pattern, demonstrating that these cells acquired the myofibroblast phenotype. Dermal fibroblasts from smooth muscle α-actin-null and wild type mice formed stress fibers and supermature focal adhesions, and generated similar amounts of contractile force in response to transforming growth factor-β1. Smooth muscle γ-actin and skeletal muscle alpha-actin were expressed in smooth muscle α-actin-null myofibroblasts, as demonstrated by immunostaining, real-time PCR, and mass spectrometry. These results demonstrate that smooth muscle α-actin is not necessary for myofibroblast formation and function and for Wound closure, and that smooth muscle γ-actin and skeletal muscle α-actin may be able to functionally compensate for the lack of smooth muscle α-actin in myofibroblasts.
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whole animal knockout of smooth muscle alpha actin does not alter Excisional Wound healing or the fibroblast to myofibroblast transition
Wound Repair and Regeneration, 2013Co-Authors: James J Tomasek, Robert J Schwartz, Carol J Haaksma, Eric W HowardAbstract:The contractile phenotype and function of myofibroblasts have been proposed to play a critical role in Wound closure. It has been hypothesized that smooth muscle α-actin expressed in myofibroblasts is critical for its formation and function. We have used smooth muscle α-actin-null mice to test this hypothesis. Full-thickness Excisional Wounds closed at a similar rate in smooth muscle α-actin-null and wild-type mice. In addition, fibroblasts in smooth muscle α-actin-null granulation tissue when immunostained with a monoclonal antibody that recognizes all muscle actin isoforms exhibited a myofibroblast-like distribution and a stress fiber-like pattern, showing that these cells acquired the myofibroblast phenotype. Dermal fibroblasts from smooth muscle α-actin-null and wild-type mice formed stress fibers and supermature focal adhesions, and generated similar amounts of contractile force in response to transforming growth factor-β1. Smooth muscle γ-actin and skeletal muscle α-actin were expressed in smooth muscle α-actin-null myofibroblasts, as shown by immunostaining, real-time polymerase chain reaction, and mass spectrometry. These results show that smooth muscle α-actin is not necessary for myofibroblast formation and function and for Wound closure, and that smooth muscle γ-actin and skeletal muscle α-actin may be able to functionally compensate for the lack of smooth muscle α-actin in myofibroblasts.
Lillian B Nanney - One of the best experts on this subject based on the ideXlab platform.
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biodegradable lysine derived polyurethane scaffolds promote healing in a porcine full thickness Excisional Wound model
Journal of Biomaterials Science-polymer Edition, 2014Co-Authors: Elizabeth J Adolph, Jeffrey M Davidson, Scott A Guelcher, Alonda C Pollins, Nancy L Cardwell, Lillian B NanneyAbstract:Lysine-derived polyurethane scaffolds (LTI-PUR) support cutaneous Wound healing in loose-skinned small animal models. Due to the physiological and anatomical similarities of human and pig skin, we investigated the capacity of LTI-PUR scaffolds to support Wound healing in a porcine Excisional Wound model. Modifications to scaffold design included the addition of carboxymethylcellulose (CMC) as a porogen to increase interconnectivity and an additional plasma treatment (Plasma) to decrease surface hydrophobicity. All LTI-PUR scaffold and formulations supported cellular infiltration and were biodegradable. At 15 days, CMC and plasma scaffolds simulated increased macrophages more so than LTI PUR or no treatment. This response was consistent with macrophage-mediated oxidative degradation of the lysine component of the scaffolds. Cell proliferation was similar in control and scaffold-treated Wounds at 8 and 15 days. Neither apoptosis nor blood vessel area density showed significant differences in the presence of...
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Biodegradable lysine-derived polyurethane scaffolds promote healing in a porcine full-thickness Excisional Wound model
Journal of biomaterials science. Polymer edition, 2014Co-Authors: Elizabeth J Adolph, Jeffrey M Davidson, Scott A Guelcher, Alonda C Pollins, Nancy L Cardwell, Lillian B NanneyAbstract:Lysine-derived polyurethane scaffolds (LTI-PUR) support cutaneous Wound healing in loose-skinned small animal models. Due to the physiological and anatomical similarities of human and pig skin, we investigated the capacity of LTI-PUR scaffolds to support Wound healing in a porcine Excisional Wound model. Modifications to scaffold design included the addition of carboxymethylcellulose (CMC) as a porogen to increase interconnectivity and an additional plasma treatment (Plasma) to decrease surface hydrophobicity. All LTI-PUR scaffold and formulations supported cellular infiltration and were biodegradable. At 15 days, CMC and plasma scaffolds simulated increased macrophages more so than LTI PUR or no treatment. This response was consistent with macrophage-mediated oxidative degradation of the lysine component of the scaffolds. Cell proliferation was similar in control and scaffold-treated Wounds at 8 and 15 days. Neither apoptosis nor blood vessel area density showed significant differences in the presence of any of the scaffold variations compared with untreated Wounds, providing further evidence that these synthetic biomaterials had no adverse effects on those pivotal Wound healing processes. During the critical phase of granulation tissue formation in full thickness porcine Excisional Wounds, LTI-PUR scaffolds supported tissue infiltration, while undergoing biodegradation. Modifications to scaffold fabrication modify the reparative process. This study emphasizes the biocompatibility and favorable cellular responses of PUR scaffolding formulations in a clinically relevant animal model.
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injectable polyurethane composite scaffolds delay Wound contraction and support cellular infiltration and remodeling in rat Excisional Wounds
Journal of Biomedical Materials Research Part A, 2012Co-Authors: Elizabeth J Adolph, Lillian B Nanney, Andrea E Hafeman, Jeffrey M Davidson, Scott A GuelcherAbstract:Injectable scaffolds present compelling opportunities for Wound repair and regeneration due to their ability to fill irregularly shaped defects and deliver biologics such as growth factors. In this study, we investigated the properties of injectable polyurethane biocomposite scaffolds and their application in cutaneous Wound repair using a rat Excisional model. The scaffolds have a minimal reaction exotherm and clinically relevant working and setting times. Moreover, the biocomposites have mechanical and thermal properties consistent with rubbery elastomers. In the rat Excisional Wound model, injection of settable biocomposite scaffolds stented the Wounds at early time points, resulting in a regenerative rather than a scarring phenotype at later time points. Measurements of Wound width and thickness revealed that the treated Wounds were less contracted at day 7 compared to blank Wounds. Analysis of cell proliferation and apoptosis showed that the scaffolds were biocompatible and supported tissue ingrowth. Myofibroblast formation and collagen fiber organization provided evidence that the scaffolds have a positive effect on extracellular matrix remodeling by disrupting the formation of an aligned matrix under elevated tension. In summary, we have developed an injectable biodegradable polyurethane biocomposite scaffold that enhances cutaneous Wound healing in a rat model.
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spatial and temporal patterns of immunoreactive transforming growth factor beta 1 beta 2 and beta 3 during Excisional Wound repair
American Journal of Pathology, 1993Co-Authors: J H Levine, Harold L Moses, Leslie I Gold, Lillian B NanneyAbstract:Transforming growth factor beta (TGF-beta) regulates cellular growth and differentiation and stimulates the synthesis and secretion of protein constituents of the extracellular matrix. Three isoforms of TGF-beta have been found in mammals. Although the biological activities of TGF-beta 1, TGF-beta 2, and TGF-beta 3 are similar at the level of cell culture, distinct in vivo functions for these molecules are emerging. To gain insight into the role of each isoform in Wound repair, antibodies specific for each isoform of TGF-beta were used to examine Excisional Wound repair. Marked differences in the temporal and spatial relationships for immunoreactive TGF-beta 1, -beta 2, and -beta 3 were noted throughout the repair process. TGF-beta 2 and TGF-beta 3 were prevalent by 24 hours after Excisional Wounding, and strong immunoreactivity was observed in the migrating epidermis. Subtle changes in immunoreactivity occurred for TGF-beta 2 and TGF-beta 3 in cells of the epidermal appendages, mesenchymal derivatives, granulation tissue, and the underlying dermis throughout Wound repair. In contrast, TGF-beta 1 was not associated with any undifferentiated cells and was not present in the dermis and most dermal structures in both nonWounded skin or Wounds until day 5 after Wounding, when re-epithelialization was complete. Following re-epithelialization, TGF-beta 2 and TGF-beta 3 were present in all four layers of stratum corneum of the differentiating epidermis. All three TGF-beta isoforms were present in mesenchymal cells and basal lamina, suggesting their role in the modulation of dermal-epidermal interaction during Wound repair. Our observations support individual in vivo function for TGF-beta isoforms in cutaneous Wound repair.
Praveen Kumar Mandapalli - One of the best experts on this subject based on the ideXlab platform.
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layer by layer thin films for co delivery of tgf β sirna and epidermal growth factor to improve Excisional Wound healing
Aaps Pharmscitech, 2017Co-Authors: Praveen Kumar Mandapalli, Suman Labala, Anup Jose, Shubhmita Bhatnagar, Renuka Janupally, Dharmarajan Sriram, Venkata Vamsi Krishna VenugantiAbstract:The major challenge with treatment of dermal Wounds is accelerating healing process, while preventing the scar formation. Herein, we have fabricated layer-by-layer (LbL) polyelectrolyte multilayer films containing epidermal growth factor (EGF) and TGF-β siRNA to improve Excisional Wound healing and decrease scar formation. The chitosan and sodium alginate LbL thin films showed 13.0 MPa tensile strength and 2.22 N/cm2 skin adhesion strength. The LbL thin films were found to be cytocompatible, where A431 epidermal keratinocytes adhered to the film and showed 86.2 ± 0.8% cell growth compared with cells cultured in the absence of LbL thin film. In contrast, LbL thin film did not promote the Escherichia coli and Staphylococcus aureus bacterial colony formation. In a C57BL/6 mouse Excisional Wound model, application of LbL thin films containing TGF-β siRNA significantly (p < 0.05) reduced the TGF-β protein expression and collagen production. The LbL thin films containing EGF showed improved Wound contraction (<9 days post excision). The co-delivery of TGF-β siRNA and EGF using LbL thin films resulted in accelerated Wound healing and decreased collagen deposition. Furthermore, the LbL thin films with TGF-β siRNA and EGF combination showed greater reepithelialization. Taken together, we have successfully demonstrated the co-delivery of TGF-β siRNA and EGF peptide using LbL thin films to promote Wound healing and decrease scar formation.
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Layer-by-Layer Thin Films for Co-Delivery of TGF-β siRNA and Epidermal Growth Factor to Improve Excisional Wound Healing.
AAPS PharmSciTech, 2016Co-Authors: Praveen Kumar Mandapalli, Suman Labala, Anup Jose, Shubhmita Bhatnagar, Renuka Janupally, Dharmarajan Sriram, Venkata Vamsi Krishna VenugantiAbstract:The major challenge with treatment of dermal Wounds is accelerating healing process, while preventing the scar formation. Herein, we have fabricated layer-by-layer (LbL) polyelectrolyte multilayer films containing epidermal growth factor (EGF) and TGF-β siRNA to improve Excisional Wound healing and decrease scar formation. The chitosan and sodium alginate LbL thin films showed 13.0 MPa tensile strength and 2.22 N/cm2 skin adhesion strength. The LbL thin films were found to be cytocompatible, where A431 epidermal keratinocytes adhered to the film and showed 86.2 ± 0.8% cell growth compared with cells cultured in the absence of LbL thin film. In contrast, LbL thin film did not promote the Escherichia coli and Staphylococcus aureus bacterial colony formation. In a C57BL/6 mouse Excisional Wound model, application of LbL thin films containing TGF-β siRNA significantly (p
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effect of pirfenidone delivered using layer by layer thin film on Excisional Wound healing
European Journal of Pharmaceutical Sciences, 2016Co-Authors: Praveen Kumar Mandapalli, Jagadeesh Bojja, Suman Labala, Venkata Vamsi Krishna VenugantiAbstract:The aim of this study was to evaluate the effect of a new anti-fibrotic agent, pirfenidone (PFD), delivered using polyelectrolyte multilayer films on Excisional Wound healing. Polyelectrolyte multilayer films were prepared by layer-by-layer (LbL) sequential adsorption of chitosan and sodium alginate. The UV-spectrophotometer, FTIR and differential scanning calorimeter were used to characterize the LbL thin films. The PFD was entrapped within the LbL thin films and its effect on Excisional Wound healing was studied in C57BL/6. The total protein, collagen content and TGF-β expression within the Wound tissue were determined after application of PFD using LbL thin films, chitosan hydrogel and polyethylene glycol hydrogel. UV-spectrophotometer and FTIR studies showed a sequential adsorption of chitosan and alginate polymer layers to form LbL thin films. The thickness of LbL thin films with 15 bilayers was found to be 15 ± 2 μm. HPLC analysis showed a PFD loading efficiency of 1.0 ± 0.1mg in 1cm(2) area of LbL thin film. In vivo Wound healing studies in C57BL/6 mice showed an accelerated (<9 days) Wound contraction after treatment with the PFD compared with blank LbL thin film and commercial povidone-iodine gel (12 days). The collagen content within the Wound tissue was significantly (p<0.05) less after treatment with PFD compared with blank film application. Western blot analysis showed gradual decrease in TGF-β expression within the Wound tissue after treatment with PFD. This study for the first time demonstrated that new anti-fibrotic agent PFD loaded in LbL thin films can be utilized for Excisional Wound healing.
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Effect of pirfenidone delivered using layer-by-layer thin film on Excisional Wound healing
European Journal of Pharmaceutical Sciences, 2016Co-Authors: Praveen Kumar Mandapalli, Jagadeesh Bojja, Suman Labala, Venkata Vamsi Krishna VenugantiAbstract:The aim of this study was to evaluate the effect of a new anti-fibrotic agent, pirfenidone (PFD), delivered using polyelectrolyte multilayer films on Excisional Wound healing. Polyelectrolyte multilayer films were prepared by layer-by-layer (LbL) sequential adsorption of chitosan and sodium alginate. The UV-spectrophotometer, FTIR and differential scanning calorimeter were used to characterize the LbL thin films. The PFD was entrapped within the LbL thin films and its effect on Excisional Wound healing was studied in C57BL/6. The total protein, collagen content and TGF-β expression within the Wound tissue were determined after application of PFD using LbL thin films, chitosan hydrogel and polyethylene glycol hydrogel. UV-spectrophotometer and FTIR studies showed a sequential adsorption of chitosan and alginate polymer layers to form LbL thin films. The thickness of LbL thin films with 15 bilayers was found to be 15 ± 2 μm. HPLC analysis showed a PFD loading efficiency of 1.0 ± 0.1 mg in 1 cm2area of LbL thin film. In vivo Wound healing studies in C57BL/6 mice showed an accelerated (
