The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform

Jodhbir S Mehta - One of the best experts on this subject based on the ideXlab platform.

  • a biodegradable sustained released tacrolimus microfilm drug delivery system for the management of allergic conjunctivitis in a mouse model
    Investigative Ophthalmology & Visual Science, 2018
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Ericia Pei Wen Teo, Hengpei Ang, Nyein Chan Lwin, Nicole Shuwen Chan, Tina Tzeeling Wong, Jodhbir S Mehta
    Abstract:

    Purpose To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-e-caprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model. Methods The in vitro and in vivo drug release profiles were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. The mice were divided into six groups (n = 12 in each): negative control (NC); positive control (PC); tacrolimus eye drops (Te); subconjunctival tacrolimus microfilm (Tm); dexamethasone eye drops (De); and tacrolimus + dexamethasone eye drops (Te+De). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed. Results The Microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 μg/day in vivo. Compared to the PC groups, the Te, Tm, De, and Te+De groups significantly reduced the allergic clinical scores throughout the study period (all P < 0.01; 0.0 ± 0.0, 5.6 ± 0.9, 3.3 ± 0.9, 3.2 ± 0.9, 1.9 ± 0.4 and 1.7 ± 0.8 for the NC, PC, Tm, Te, De, and Te+De groups, respectively, at 4 weeks after treatment). The suppressed eosinophils, CD11c, CD4, and IL-4 expression were also observed in all treatment groups, with more reduction in the Te+De group. Conclusions Tacrolimus-loaded Microfilms display good biocompatibility and desirable sustained drug release. It was as effective as conventional tacrolimus eye drops on the treatment of allergic conjunctivitis, providing a promising clinically applicable alternative for controlling allergic disease activity, or other immune-mediated ocular diseases.

  • A Biodegradable, Sustained-Released, Prednisolone Acetate Microfilm Drug Delivery System Effectively Prolongs Corneal Allograft Survival in the Rat Keratoplasty Model
    2016
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006– 0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was.28 days in group 2, 9.960.8 days in group 3, 26.862.7 days in group 4, and 26.463.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P,0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loade

  • a biodegradable sustained released prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model
    PLOS ONE, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006–0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  • optimization of subconjunctival biodegradable Microfilms for sustained drug delivery to the anterior segment in a small animal model
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Purpose We evaluated a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly[d,l-lactide-co-e-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics in vitro and in vivo. Methods Blank and 40% PA-loaded PLC Microfilms with a diameter of 2 mm were fabricated, and the degradation and drug release profiles of the Microfilms were characterized in vitro and in vivo. The Microfilms were implanted into the subconjunctival space of Lewis rats (n = 48). All eyes were assessed clinically using slit-lamp biomicroscopy, and graded with Hackett-McDonald ocular scoring system and anterior segment optical coherence tomography. Histologic and immunohistochemical analyses were performed comparing blank and PA-loaded microfilm groups. PA concentrations in the aqueous humor were determined by HPLC. Results Subconjunctivally-implanted PLC Microfilms were able to deliver PA in a sustained manner over 3 months, with a steady rate of 0.002 mg/d in vivo. Eyes with either blank or PA-loaded implanted Microfilms showed a very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the Microfilms, with significantly less CD11c cells at 2 and 4 weeks (P = 0.001 and P = 0.002), and collagen formation at 2 weeks (P = 0.001) in the PA-loaded microfilm group. Anterior chamber PA levels were achieved, with concentrations at 76.7 ± 5.9, 70.3 ± 2.3, and 42.7 ± 4.1 ng/mL at 2, 4, and 12 weeks, respectively. Conclusions PA-loaded PLC Microfilms display good biocompatibility, feasibility, and desirable sustained drug release profiles, and have the potential to exhibit antifibrotic and anti-inflammatory effects. This device is applicable to use in small animal models of anterior segment inflammation.

Yuchi Liu - One of the best experts on this subject based on the ideXlab platform.

  • a biodegradable sustained released tacrolimus microfilm drug delivery system for the management of allergic conjunctivitis in a mouse model
    Investigative Ophthalmology & Visual Science, 2018
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Ericia Pei Wen Teo, Hengpei Ang, Nyein Chan Lwin, Nicole Shuwen Chan, Tina Tzeeling Wong, Jodhbir S Mehta
    Abstract:

    Purpose To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-e-caprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model. Methods The in vitro and in vivo drug release profiles were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. The mice were divided into six groups (n = 12 in each): negative control (NC); positive control (PC); tacrolimus eye drops (Te); subconjunctival tacrolimus microfilm (Tm); dexamethasone eye drops (De); and tacrolimus + dexamethasone eye drops (Te+De). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed. Results The Microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 μg/day in vivo. Compared to the PC groups, the Te, Tm, De, and Te+De groups significantly reduced the allergic clinical scores throughout the study period (all P < 0.01; 0.0 ± 0.0, 5.6 ± 0.9, 3.3 ± 0.9, 3.2 ± 0.9, 1.9 ± 0.4 and 1.7 ± 0.8 for the NC, PC, Tm, Te, De, and Te+De groups, respectively, at 4 weeks after treatment). The suppressed eosinophils, CD11c, CD4, and IL-4 expression were also observed in all treatment groups, with more reduction in the Te+De group. Conclusions Tacrolimus-loaded Microfilms display good biocompatibility and desirable sustained drug release. It was as effective as conventional tacrolimus eye drops on the treatment of allergic conjunctivitis, providing a promising clinically applicable alternative for controlling allergic disease activity, or other immune-mediated ocular diseases.

  • A Biodegradable, Sustained-Released, Prednisolone Acetate Microfilm Drug Delivery System Effectively Prolongs Corneal Allograft Survival in the Rat Keratoplasty Model
    2016
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006– 0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was.28 days in group 2, 9.960.8 days in group 3, 26.862.7 days in group 4, and 26.463.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P,0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loade

  • a biodegradable sustained released prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model
    PLOS ONE, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006–0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  • optimization of subconjunctival biodegradable Microfilms for sustained drug delivery to the anterior segment in a small animal model
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Purpose We evaluated a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly[d,l-lactide-co-e-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics in vitro and in vivo. Methods Blank and 40% PA-loaded PLC Microfilms with a diameter of 2 mm were fabricated, and the degradation and drug release profiles of the Microfilms were characterized in vitro and in vivo. The Microfilms were implanted into the subconjunctival space of Lewis rats (n = 48). All eyes were assessed clinically using slit-lamp biomicroscopy, and graded with Hackett-McDonald ocular scoring system and anterior segment optical coherence tomography. Histologic and immunohistochemical analyses were performed comparing blank and PA-loaded microfilm groups. PA concentrations in the aqueous humor were determined by HPLC. Results Subconjunctivally-implanted PLC Microfilms were able to deliver PA in a sustained manner over 3 months, with a steady rate of 0.002 mg/d in vivo. Eyes with either blank or PA-loaded implanted Microfilms showed a very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the Microfilms, with significantly less CD11c cells at 2 and 4 weeks (P = 0.001 and P = 0.002), and collagen formation at 2 weeks (P = 0.001) in the PA-loaded microfilm group. Anterior chamber PA levels were achieved, with concentrations at 76.7 ± 5.9, 70.3 ± 2.3, and 42.7 ± 4.1 ng/mL at 2, 4, and 12 weeks, respectively. Conclusions PA-loaded PLC Microfilms display good biocompatibility, feasibility, and desirable sustained drug release profiles, and have the potential to exhibit antifibrotic and anti-inflammatory effects. This device is applicable to use in small animal models of anterior segment inflammation.

Subbu S Venkatraman - One of the best experts on this subject based on the ideXlab platform.

  • a biodegradable sustained released tacrolimus microfilm drug delivery system for the management of allergic conjunctivitis in a mouse model
    Investigative Ophthalmology & Visual Science, 2018
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Ericia Pei Wen Teo, Hengpei Ang, Nyein Chan Lwin, Nicole Shuwen Chan, Tina Tzeeling Wong, Jodhbir S Mehta
    Abstract:

    Purpose To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-e-caprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model. Methods The in vitro and in vivo drug release profiles were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. The mice were divided into six groups (n = 12 in each): negative control (NC); positive control (PC); tacrolimus eye drops (Te); subconjunctival tacrolimus microfilm (Tm); dexamethasone eye drops (De); and tacrolimus + dexamethasone eye drops (Te+De). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed. Results The Microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 μg/day in vivo. Compared to the PC groups, the Te, Tm, De, and Te+De groups significantly reduced the allergic clinical scores throughout the study period (all P < 0.01; 0.0 ± 0.0, 5.6 ± 0.9, 3.3 ± 0.9, 3.2 ± 0.9, 1.9 ± 0.4 and 1.7 ± 0.8 for the NC, PC, Tm, Te, De, and Te+De groups, respectively, at 4 weeks after treatment). The suppressed eosinophils, CD11c, CD4, and IL-4 expression were also observed in all treatment groups, with more reduction in the Te+De group. Conclusions Tacrolimus-loaded Microfilms display good biocompatibility and desirable sustained drug release. It was as effective as conventional tacrolimus eye drops on the treatment of allergic conjunctivitis, providing a promising clinically applicable alternative for controlling allergic disease activity, or other immune-mediated ocular diseases.

  • A Biodegradable, Sustained-Released, Prednisolone Acetate Microfilm Drug Delivery System Effectively Prolongs Corneal Allograft Survival in the Rat Keratoplasty Model
    2016
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006– 0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was.28 days in group 2, 9.960.8 days in group 3, 26.862.7 days in group 4, and 26.463.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P,0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loade

  • Evaluation of a Prednisolone Acetate-Loaded Subconjunctival Implant for the Treatment of Recurrent Uveitis in a Rabbit Model
    2016
    Co-Authors: Marcus Ang, Peng Yan, Subbu S Venkatraman, Cheewai Wong, Soon-phaik Chee, Tina T Wong
    Abstract:

    Aim: To assess the efficacy of a biodegradable, prednisolone acetate implant in a rabbit uveitis model. Methods: Randomized, controlled study of biodegradable Microfilms preloaded with prednisolone acetate (PA) in a rabbit uveitis model. Experimental uveitis was induced by unilateral intravitreal injection of Mycobacterium tuberculosis H37Ra antigen (50 ug; 1 ug/uL) in preimmunized rabbits. PA-loaded poly[d,l-lactide-co-e-caprolactone] (PLC) Microfilms (n = 10) and blank Microfilms (n = 6) were implanted subconjunctivally. An estimate of PA release in vivo was calculated from measured residual PA amounts in Microfilms after the rabbits were sacrificed. The eyes were clinically monitored for ocular inflammation for 28 days. Histopathological examination of the enucleated eyes was performed at the end of the study period. Results: In vitro studies revealed that sandwich PA-loaded microfilm formulations exhibited higher release kinetic compared to homogenous PA-loaded Microfilms. The 60–40–60 % microfilm released an average of 0.034 mg/day of PA over the period of 60 days in vitro; and we found that approximately 0.12 mg/day PA was released in vivo. Animals implanted with the PA-loaded Microfilms exhibited significantly lowered median inflammatory scores when compared against the control group in this model for recurrent uveitis (P,0.001). The implants were clinically well tolerated by all the animals. Histology results showed no significant scarring or inflammation around the PA-loaded Microfilms

  • a biodegradable sustained released prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model
    PLOS ONE, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006–0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  • optimization of subconjunctival biodegradable Microfilms for sustained drug delivery to the anterior segment in a small animal model
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Purpose We evaluated a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly[d,l-lactide-co-e-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics in vitro and in vivo. Methods Blank and 40% PA-loaded PLC Microfilms with a diameter of 2 mm were fabricated, and the degradation and drug release profiles of the Microfilms were characterized in vitro and in vivo. The Microfilms were implanted into the subconjunctival space of Lewis rats (n = 48). All eyes were assessed clinically using slit-lamp biomicroscopy, and graded with Hackett-McDonald ocular scoring system and anterior segment optical coherence tomography. Histologic and immunohistochemical analyses were performed comparing blank and PA-loaded microfilm groups. PA concentrations in the aqueous humor were determined by HPLC. Results Subconjunctivally-implanted PLC Microfilms were able to deliver PA in a sustained manner over 3 months, with a steady rate of 0.002 mg/d in vivo. Eyes with either blank or PA-loaded implanted Microfilms showed a very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the Microfilms, with significantly less CD11c cells at 2 and 4 weeks (P = 0.001 and P = 0.002), and collagen formation at 2 weeks (P = 0.001) in the PA-loaded microfilm group. Anterior chamber PA levels were achieved, with concentrations at 76.7 ± 5.9, 70.3 ± 2.3, and 42.7 ± 4.1 ng/mL at 2, 4, and 12 weeks, respectively. Conclusions PA-loaded PLC Microfilms display good biocompatibility, feasibility, and desirable sustained drug release profiles, and have the potential to exhibit antifibrotic and anti-inflammatory effects. This device is applicable to use in small animal models of anterior segment inflammation.

Nyein Chan Lwin - One of the best experts on this subject based on the ideXlab platform.

  • a biodegradable sustained released tacrolimus microfilm drug delivery system for the management of allergic conjunctivitis in a mouse model
    Investigative Ophthalmology & Visual Science, 2018
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Ericia Pei Wen Teo, Hengpei Ang, Nyein Chan Lwin, Nicole Shuwen Chan, Tina Tzeeling Wong, Jodhbir S Mehta
    Abstract:

    Purpose To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-e-caprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model. Methods The in vitro and in vivo drug release profiles were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. The mice were divided into six groups (n = 12 in each): negative control (NC); positive control (PC); tacrolimus eye drops (Te); subconjunctival tacrolimus microfilm (Tm); dexamethasone eye drops (De); and tacrolimus + dexamethasone eye drops (Te+De). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed. Results The Microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 μg/day in vivo. Compared to the PC groups, the Te, Tm, De, and Te+De groups significantly reduced the allergic clinical scores throughout the study period (all P < 0.01; 0.0 ± 0.0, 5.6 ± 0.9, 3.3 ± 0.9, 3.2 ± 0.9, 1.9 ± 0.4 and 1.7 ± 0.8 for the NC, PC, Tm, Te, De, and Te+De groups, respectively, at 4 weeks after treatment). The suppressed eosinophils, CD11c, CD4, and IL-4 expression were also observed in all treatment groups, with more reduction in the Te+De group. Conclusions Tacrolimus-loaded Microfilms display good biocompatibility and desirable sustained drug release. It was as effective as conventional tacrolimus eye drops on the treatment of allergic conjunctivitis, providing a promising clinically applicable alternative for controlling allergic disease activity, or other immune-mediated ocular diseases.

  • A Biodegradable, Sustained-Released, Prednisolone Acetate Microfilm Drug Delivery System Effectively Prolongs Corneal Allograft Survival in the Rat Keratoplasty Model
    2016
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006– 0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was.28 days in group 2, 9.960.8 days in group 3, 26.862.7 days in group 4, and 26.463.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P,0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loade

  • a biodegradable sustained released prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model
    PLOS ONE, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006–0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  • optimization of subconjunctival biodegradable Microfilms for sustained drug delivery to the anterior segment in a small animal model
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Purpose We evaluated a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly[d,l-lactide-co-e-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics in vitro and in vivo. Methods Blank and 40% PA-loaded PLC Microfilms with a diameter of 2 mm were fabricated, and the degradation and drug release profiles of the Microfilms were characterized in vitro and in vivo. The Microfilms were implanted into the subconjunctival space of Lewis rats (n = 48). All eyes were assessed clinically using slit-lamp biomicroscopy, and graded with Hackett-McDonald ocular scoring system and anterior segment optical coherence tomography. Histologic and immunohistochemical analyses were performed comparing blank and PA-loaded microfilm groups. PA concentrations in the aqueous humor were determined by HPLC. Results Subconjunctivally-implanted PLC Microfilms were able to deliver PA in a sustained manner over 3 months, with a steady rate of 0.002 mg/d in vivo. Eyes with either blank or PA-loaded implanted Microfilms showed a very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the Microfilms, with significantly less CD11c cells at 2 and 4 weeks (P = 0.001 and P = 0.002), and collagen formation at 2 weeks (P = 0.001) in the PA-loaded microfilm group. Anterior chamber PA levels were achieved, with concentrations at 76.7 ± 5.9, 70.3 ± 2.3, and 42.7 ± 4.1 ng/mL at 2, 4, and 12 weeks, respectively. Conclusions PA-loaded PLC Microfilms display good biocompatibility, feasibility, and desirable sustained drug release profiles, and have the potential to exhibit antifibrotic and anti-inflammatory effects. This device is applicable to use in small animal models of anterior segment inflammation.

Tina T Wong - One of the best experts on this subject based on the ideXlab platform.

  • A Biodegradable, Sustained-Released, Prednisolone Acetate Microfilm Drug Delivery System Effectively Prolongs Corneal Allograft Survival in the Rat Keratoplasty Model
    2016
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006– 0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was.28 days in group 2, 9.960.8 days in group 3, 26.862.7 days in group 4, and 26.463.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P,0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loade

  • Evaluation of a Prednisolone Acetate-Loaded Subconjunctival Implant for the Treatment of Recurrent Uveitis in a Rabbit Model
    2016
    Co-Authors: Marcus Ang, Peng Yan, Subbu S Venkatraman, Cheewai Wong, Soon-phaik Chee, Tina T Wong
    Abstract:

    Aim: To assess the efficacy of a biodegradable, prednisolone acetate implant in a rabbit uveitis model. Methods: Randomized, controlled study of biodegradable Microfilms preloaded with prednisolone acetate (PA) in a rabbit uveitis model. Experimental uveitis was induced by unilateral intravitreal injection of Mycobacterium tuberculosis H37Ra antigen (50 ug; 1 ug/uL) in preimmunized rabbits. PA-loaded poly[d,l-lactide-co-e-caprolactone] (PLC) Microfilms (n = 10) and blank Microfilms (n = 6) were implanted subconjunctivally. An estimate of PA release in vivo was calculated from measured residual PA amounts in Microfilms after the rabbits were sacrificed. The eyes were clinically monitored for ocular inflammation for 28 days. Histopathological examination of the enucleated eyes was performed at the end of the study period. Results: In vitro studies revealed that sandwich PA-loaded microfilm formulations exhibited higher release kinetic compared to homogenous PA-loaded Microfilms. The 60–40–60 % microfilm released an average of 0.034 mg/day of PA over the period of 60 days in vitro; and we found that approximately 0.12 mg/day PA was released in vivo. Animals implanted with the PA-loaded Microfilms exhibited significantly lowered median inflammatory scores when compared against the control group in this model for recurrent uveitis (P,0.001). The implants were clinically well tolerated by all the animals. Histology results showed no significant scarring or inflammation around the PA-loaded Microfilms

  • a biodegradable sustained released prednisolone acetate microfilm drug delivery system effectively prolongs corneal allograft survival in the rat keratoplasty model
    PLOS ONE, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Frequent and long-term use of topical corticosteroids after corneal transplantation is necessary to prevent graft rejection. However, it relies heavily on patient compliance, and sustained therapeutic drug levels are often not achieved with administration of topical eye drops. A biodegradable drug delivery system with a controlled and sustained drug release may circumvent these limitations. In this study, we investigated the efficacy of a prednisolone acetate (PA)-loaded poly (d,l-lactide-co-e-caprolactone) (PLC) microfilm drug delivery system on promoting the survival of allogeneic grafts after penetrating keratoplasty (PK) using a rat model. The drug release profiles of the Microfilms were characterized (group 1). Subsequently, forty-eight PK were performed in four experimental groups: syngeneic control grafts (group 2), allogeneic control grafts (group 3), allogeneic grafts with subconjunctivally-implanted PA microfilm (group 4), and allogeneic grafts with PA eye drops (group 5; n = 12 in each). PA-loaded microfilm achieved a sustained and steady release at a rate of 0.006–0.009 mg/day, with a consistent aqueous drug concentration of 207–209 ng/ml. The mean survival days was >28 days in group 2, 9.9±0.8 days in group 3, 26.8±2.7 days in group 4, and 26.4±3.4 days in group 5 (P = 0.023 and P = 0.027 compared with group 3). Statistically significant decrease in CD4+, CD163+, CD 25+, and CD54+ cell infiltration was observed in group 4 and group 5 compared with group 3 (P<0.001). There was no significant difference in the mean survival and immunohistochemical analysis between group 4 and group 5. These results showed that sustained PA-loaded microfilm effectively prolongs corneal allograft survival. It is as effective as conventional PA eye drops, providing a promising clinically applicable alternative for patients undergoing corneal transplantation.

  • optimization of subconjunctival biodegradable Microfilms for sustained drug delivery to the anterior segment in a small animal model
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Yuchi Liu, Subbu S Venkatraman, Tina T Wong, Nyein Chan Lwin, Yan Peng, Jodhbir S Mehta
    Abstract:

    Purpose We evaluated a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly[d,l-lactide-co-e-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics in vitro and in vivo. Methods Blank and 40% PA-loaded PLC Microfilms with a diameter of 2 mm were fabricated, and the degradation and drug release profiles of the Microfilms were characterized in vitro and in vivo. The Microfilms were implanted into the subconjunctival space of Lewis rats (n = 48). All eyes were assessed clinically using slit-lamp biomicroscopy, and graded with Hackett-McDonald ocular scoring system and anterior segment optical coherence tomography. Histologic and immunohistochemical analyses were performed comparing blank and PA-loaded microfilm groups. PA concentrations in the aqueous humor were determined by HPLC. Results Subconjunctivally-implanted PLC Microfilms were able to deliver PA in a sustained manner over 3 months, with a steady rate of 0.002 mg/d in vivo. Eyes with either blank or PA-loaded implanted Microfilms showed a very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the Microfilms, with significantly less CD11c cells at 2 and 4 weeks (P = 0.001 and P = 0.002), and collagen formation at 2 weeks (P = 0.001) in the PA-loaded microfilm group. Anterior chamber PA levels were achieved, with concentrations at 76.7 ± 5.9, 70.3 ± 2.3, and 42.7 ± 4.1 ng/mL at 2, 4, and 12 weeks, respectively. Conclusions PA-loaded PLC Microfilms display good biocompatibility, feasibility, and desirable sustained drug release profiles, and have the potential to exhibit antifibrotic and anti-inflammatory effects. This device is applicable to use in small animal models of anterior segment inflammation.

  • evaluation of sustained release of plc loaded prednisolone acetate microfilm on postoperative inflammation in an experimental model of glaucoma filtration surgery
    Current Eye Research, 2011
    Co-Authors: Marcus Ang, Peng Yan, Ma Zhen, Selin Foo, Subbu S Venkatraman, Tina T Wong
    Abstract:

    Purpose: To evaluate the effect of a biodegradable microfilm with sustained release of prednisolone acetate (PA) on postoperative wound healing after experimental glaucoma filtration surgery (GFS).Methods: Biodegradable Microfilms composed of poly (d-, l-lactide-co-caprolactone) (PLC) were fabricated and then pre-loaded PA-20% total weight. Fourteen New Zealand White rabbits were randomly divided into 3 treatment groups: GFS alone (n = 4), GFS with PLC Microfilms (n = 4) and GFS with PA-loaded microfilm (n = 6). Microfilms were inserted subconjunctivally, adjacent to the filtering surgical site. We monitored all eyes with slit-lamp examination, bleb photography and anterior segment optical coherence tomography (AS-OCT). Histology with immunohistochemistry was performed to determine the presence of any inflammation.Results: Prednisolone acetate 20%-loaded Microfilms exhibited steady, sustained release in vitro. Eyes implanted with PA-loaded Microfilms showed a significantly better bleb survival (100% vs. 3...