Sustained Delivery

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Jiangang Wang - One of the best experts on this subject based on the ideXlab platform.

  • Sustained Delivery of chondroitinase abc by poly propylene carbonate chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection
    Brain Research, 2015
    Co-Authors: Shilei Ni, Xingang Li, Hongxu Qi, Shanying Huang, Jiangang Wang
    Abstract:

    We describe the Sustained Delivery of chondroitinase ABC (ChABC) in the hemisected spinal cord using polypropylene carbonate (PPC) electrospun fibers with chitosan (CS) microspheres as a vehicle. PPC and ChABC-loaded CS microspheres were mixed with acetonitrile, and micron fibers were generated by electrospinning. ChABC release was assessed in vitro with high-performance liquid chromatography (HPLC) and revealed stabilized and prolonged release. Moreover, the released ChABC showed Sustained activity. PPC-CS micron fibers with or without ChABC were then implanted into a hemisected thoracic spinal cord. In the following 4 weeks, we examined functional recovery and performed immunohistochemical analyses. We found that Sustained Delivery of ChABC promoted axon sprouting and functional recovery and reduced glial scarring; PPC-CS micron fibers without ChABC did not show these effects. The present findings suggest that PPC-CS micron fibers containing ChABC are a feasible option for spinal cord injury treatment. Furthermore, the system described here may be useful for local Delivery of other therapeutic agents.

  • Sustained Delivery of dbcamp by poly propylene carbonate micron fibers promotes axonal regenerative sprouting and functional recovery after spinal cord hemisection
    Brain Research, 2013
    Co-Authors: Shilei Ni, Xingang Li, Hongxu Qi, Jiangang Wang
    Abstract:

    This study describes the use of poly(propylene carbonate) (PPC) electrospun fibers as vehicle for the Sustained Delivery of dibutyryl cyclic adenosine monophosphate (dbcAMP) to the hemisected spinal cord. The dbcAMP and PPC were uniformly mixed with acetonitrile; then, electrospinning was used to generate micron fibers. The release of dbcAMP was assessed by ELISA in vitro. Our results showed that the encapsulation of dbcAMP in the fibers led to stable and prolonged release in vitro. The PPC micron fibers containing dbcAMP and the PPC micron fibers without dbcAMP were then implanted into the hemisected thoracic spinal cord, followed by testing of the functional recovery and immunohistochemistry. Compared with the control group, Sustained Delivery of dbcAMP promoted axonal regenerative sprouting and functional recovery and reduced glial scar formation, and the PPC micron fibers without dbcAMP did not have these effects. Our findings demonstrated the feasibility of using PPC electrospun fibers containing dbcAMP for spinal cord injury. The approach described here also will provide a platform for the potential Delivery of other axon-growth-promoting or scar-inhibiting agents.

Paul Ashton - One of the best experts on this subject based on the ideXlab platform.

  • Sustained Delivery fluocinolone acetonide vitreous implants long term benefit in patients with chronic diabetic macular edema
    Ophthalmology, 2014
    Co-Authors: Jose Cunhavaz, Paul Ashton, Peter A Campochiaro, Frank G Holz, Raymond Iezzi, Pravin U Dugel, M Weber, Ronald P Danis, Baruch D Kuppermann, Clare Bailey
    Abstract:

    Purpose To present the safety and efficacy of intravitreal implants releasing 0.2 μg/day fluocinolone acetonide (FAc) in patients with chronic versus nonchronic diabetic macular edema (DME). To assess ocular characteristics, anatomic changes, and re-treatment and ancillary therapies that may explain the differential treatment effect seen with intravitreal implants releasing FAc 0.2 μg/day in patients with chronic and nonchronic DME. An overall benefit-to-risk assessment for the FAc 0.2-μg/day and FAc 0.5-μg/day doses has been reported previously. Design Preplanned subgroup analysis of chronic (duration of diagnosis, ≥3 years) and nonchronic (duration of diagnosis, Participants Patients with persistent DME despite 1 or more macular laser treatment were randomized 1:2:2 to sham injection (n = 185), FAc 0.2 μg/day (n = 375), or FAc 0.5 μg/day (n = 393). Methods Patients received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on re-treatment criteria, additional masked study drug could be given after 1 year. Main Outcome Measures Percentage of patients with improvement of 15 letters or more from baseline. Secondary outcomes included other parameters of visual function and foveal thickness. Results At month 36, the difference between FAc 0.2 μg/day and sham control in the percentage of patients who gained 15 letters or more was significantly greater in chronic DME patients (FAc 0.2 μg/day, 34.0% vs. sham, 13.4%; P P  = 0.275). The greater response in patients with chronic DME was not associated with baseline ocular characteristics, changes in anatomic features, or differences in re-treatment or ancillary therapies. The ocular adverse event profile for FAc 0.2 μg/day was similar regardless of DME duration. Conclusions This is the first published analysis correlating duration of diagnosis of DME with treatment effect. In patients with chronic DME, FAc 0.2 μg/day provides substantial visual benefit for up to 3 years and would provide an option for patients who do not respond to other therapy.

  • photoreceptor neuroprotection in rcs rats via low dose intravitreal Sustained Delivery of fluocinolone acetonide
    Investigative Ophthalmology & Visual Science, 2009
    Co-Authors: Inna V Glybina, Paul Ashton, A Kennedy, Gary W Abrams, Raymond Iezzi
    Abstract:

    PURPOSE: To study the neuroprotective effects of intravitreal fluocinolone acetonide (FA) in Royal College of Surgeons (RCS) rats. METHODS: Five-week-old RCS rats were divided into four groups: 0.5 microg/d FA-loaded intravitreal drug-Delivery implant (IDDI); 0.2 microg/d FA-loaded IDDI; inactive IDDI; and nonsurgical control. Electroretinography (ERG) and intraocular pressure (IOP) measurements were performed before surgery and weekly thereafter. Thicknesses of the retinal outer (ONL) and inner (INL) nuclear layers were evaluated at 9 weeks of age. ED-1-labeled activated microglia were counted. Total microglial cell counts were made by using Iba-1 antibody labeling. RESULTS: At 9 weeks, control groups demonstrated an 80% reduction in ERG amplitudes (P < 0.001 for both groups). FA-treated groups demonstrated no statistically significant attenuation of ERG amplitudes at the end of the study, compared with the initial ERGs. Intraocular pressure (IOP) remained normal in all groups. ONL thickness in FA 0.2 microg/d-treated eyes was 2.1 +/- 0.5 times greater than in nonsurgical eyes (P < 0.001) and 3.4 +/- 0.7 times greater than in inactive IDDI-treated eyes (P < 0.0001). In FA 0.5 microg/d-treated eyes, ONL thickness was 1.5 +/- 0.1 times higher than in nonsurgical controls (P < 0.05) and 2.4 +/- 0.4 times higher than in inactive IDDI-treated eyes (P < 0.01). INL thickness was not different among groups. FA-treated eyes demonstrated significantly fewer activated microglia (P < 0.001) and overall number of microglia in the photoreceptor and outer debris zone layers (P < 0.001), compared with control groups. CONCLUSIONS: Chronic intravitreal infusion of FA is neuroprotective in RCS rats, preserves ONL morphology and ERG amplitudes and reduces retinal neuroinflammation. These findings may have a therapeutic role in human photoreceptor cell degenerations.

  • safety and pharmacokinetics of an intraocular fluocinolone acetonide Sustained Delivery device
    Investigative Ophthalmology & Visual Science, 2000
    Co-Authors: Glenn J Jaffe, Chang Hao Yang, Hong Guo, John P Denny, Cristiana Lima, Paul Ashton
    Abstract:

    PURPOSE To determine the safety and pharmacokinetics of an intraocular fluocinolone acetonide Sustained drug Delivery device. METHODS Nonbiodegradable drug Delivery devices containing 2 or 15 mg of a synthetic corticosteroid, fluocinolone acetonide, were constructed. The long-term in vitro release rates of these devices were determined in protein-free buffer or buffer containing 50% plasma protein. Fifteen-milligram devices were also implanted into the vitreous cavities of rabbit eyes. Intravitreal drug levels, the amount of drug remaining in explanted devices, and the release rate of explanted devices were determined over a 1-year time period. Drug toxicity was assessed over this same time period by slit lamp examination, indirect ophthalmoscopy, electroretinography, and histologic examination. RESULTS The drug release rates for the 2-mg device, 1.9 +/- 0.25 microg/d, and for the 15-mg device, 2.2 +/- 0.6 microg/d, remained linear over the 6-month and 45-day testing period, respectively. The release rate increased by approximately 20% when devices were transferred from protein-free buffer to buffer that contained protein (P: < 0.0001). Vitreous levels remained fairly constant (0.10-0.21 microg/ml) over a 1-year period. No drug was present in the aqueous humor during this time period. Based on the device release rates, the predicted life span of the 2- and 15-mg devices are 2.7 and 18.6 years, respectively. There was no evidence of drug toxicity by clinical examination, electroretinography, or histologic examination. CONCLUSIONS It is feasible to construct a nontoxic fluocinolone acetonide drug Delivery device that reproducibly releases fluocinolone acetonide in a linear manner over an extended period. These devices show great promise in the treatment of ocular diseases such as uveitis, which are often managed with chronic corticosteroid therapy.

Shilei Ni - One of the best experts on this subject based on the ideXlab platform.

  • Sustained Delivery of chondroitinase abc by poly propylene carbonate chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection
    Brain Research, 2015
    Co-Authors: Shilei Ni, Xingang Li, Hongxu Qi, Shanying Huang, Jiangang Wang
    Abstract:

    We describe the Sustained Delivery of chondroitinase ABC (ChABC) in the hemisected spinal cord using polypropylene carbonate (PPC) electrospun fibers with chitosan (CS) microspheres as a vehicle. PPC and ChABC-loaded CS microspheres were mixed with acetonitrile, and micron fibers were generated by electrospinning. ChABC release was assessed in vitro with high-performance liquid chromatography (HPLC) and revealed stabilized and prolonged release. Moreover, the released ChABC showed Sustained activity. PPC-CS micron fibers with or without ChABC were then implanted into a hemisected thoracic spinal cord. In the following 4 weeks, we examined functional recovery and performed immunohistochemical analyses. We found that Sustained Delivery of ChABC promoted axon sprouting and functional recovery and reduced glial scarring; PPC-CS micron fibers without ChABC did not show these effects. The present findings suggest that PPC-CS micron fibers containing ChABC are a feasible option for spinal cord injury treatment. Furthermore, the system described here may be useful for local Delivery of other therapeutic agents.

  • Sustained Delivery of dbcamp by poly propylene carbonate micron fibers promotes axonal regenerative sprouting and functional recovery after spinal cord hemisection
    Brain Research, 2013
    Co-Authors: Shilei Ni, Xingang Li, Hongxu Qi, Jiangang Wang
    Abstract:

    This study describes the use of poly(propylene carbonate) (PPC) electrospun fibers as vehicle for the Sustained Delivery of dibutyryl cyclic adenosine monophosphate (dbcAMP) to the hemisected spinal cord. The dbcAMP and PPC were uniformly mixed with acetonitrile; then, electrospinning was used to generate micron fibers. The release of dbcAMP was assessed by ELISA in vitro. Our results showed that the encapsulation of dbcAMP in the fibers led to stable and prolonged release in vitro. The PPC micron fibers containing dbcAMP and the PPC micron fibers without dbcAMP were then implanted into the hemisected thoracic spinal cord, followed by testing of the functional recovery and immunohistochemistry. Compared with the control group, Sustained Delivery of dbcAMP promoted axonal regenerative sprouting and functional recovery and reduced glial scar formation, and the PPC micron fibers without dbcAMP did not have these effects. Our findings demonstrated the feasibility of using PPC electrospun fibers containing dbcAMP for spinal cord injury. The approach described here also will provide a platform for the potential Delivery of other axon-growth-promoting or scar-inhibiting agents.

Xingang Li - One of the best experts on this subject based on the ideXlab platform.

  • Sustained Delivery of chondroitinase abc by poly propylene carbonate chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection
    Brain Research, 2015
    Co-Authors: Shilei Ni, Xingang Li, Hongxu Qi, Shanying Huang, Jiangang Wang
    Abstract:

    We describe the Sustained Delivery of chondroitinase ABC (ChABC) in the hemisected spinal cord using polypropylene carbonate (PPC) electrospun fibers with chitosan (CS) microspheres as a vehicle. PPC and ChABC-loaded CS microspheres were mixed with acetonitrile, and micron fibers were generated by electrospinning. ChABC release was assessed in vitro with high-performance liquid chromatography (HPLC) and revealed stabilized and prolonged release. Moreover, the released ChABC showed Sustained activity. PPC-CS micron fibers with or without ChABC were then implanted into a hemisected thoracic spinal cord. In the following 4 weeks, we examined functional recovery and performed immunohistochemical analyses. We found that Sustained Delivery of ChABC promoted axon sprouting and functional recovery and reduced glial scarring; PPC-CS micron fibers without ChABC did not show these effects. The present findings suggest that PPC-CS micron fibers containing ChABC are a feasible option for spinal cord injury treatment. Furthermore, the system described here may be useful for local Delivery of other therapeutic agents.

  • Sustained Delivery of dbcamp by poly propylene carbonate micron fibers promotes axonal regenerative sprouting and functional recovery after spinal cord hemisection
    Brain Research, 2013
    Co-Authors: Shilei Ni, Xingang Li, Hongxu Qi, Jiangang Wang
    Abstract:

    This study describes the use of poly(propylene carbonate) (PPC) electrospun fibers as vehicle for the Sustained Delivery of dibutyryl cyclic adenosine monophosphate (dbcAMP) to the hemisected spinal cord. The dbcAMP and PPC were uniformly mixed with acetonitrile; then, electrospinning was used to generate micron fibers. The release of dbcAMP was assessed by ELISA in vitro. Our results showed that the encapsulation of dbcAMP in the fibers led to stable and prolonged release in vitro. The PPC micron fibers containing dbcAMP and the PPC micron fibers without dbcAMP were then implanted into the hemisected thoracic spinal cord, followed by testing of the functional recovery and immunohistochemistry. Compared with the control group, Sustained Delivery of dbcAMP promoted axonal regenerative sprouting and functional recovery and reduced glial scar formation, and the PPC micron fibers without dbcAMP did not have these effects. Our findings demonstrated the feasibility of using PPC electrospun fibers containing dbcAMP for spinal cord injury. The approach described here also will provide a platform for the potential Delivery of other axon-growth-promoting or scar-inhibiting agents.

Hongxu Qi - One of the best experts on this subject based on the ideXlab platform.

  • Sustained Delivery of chondroitinase abc by poly propylene carbonate chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection
    Brain Research, 2015
    Co-Authors: Shilei Ni, Xingang Li, Hongxu Qi, Shanying Huang, Jiangang Wang
    Abstract:

    We describe the Sustained Delivery of chondroitinase ABC (ChABC) in the hemisected spinal cord using polypropylene carbonate (PPC) electrospun fibers with chitosan (CS) microspheres as a vehicle. PPC and ChABC-loaded CS microspheres were mixed with acetonitrile, and micron fibers were generated by electrospinning. ChABC release was assessed in vitro with high-performance liquid chromatography (HPLC) and revealed stabilized and prolonged release. Moreover, the released ChABC showed Sustained activity. PPC-CS micron fibers with or without ChABC were then implanted into a hemisected thoracic spinal cord. In the following 4 weeks, we examined functional recovery and performed immunohistochemical analyses. We found that Sustained Delivery of ChABC promoted axon sprouting and functional recovery and reduced glial scarring; PPC-CS micron fibers without ChABC did not show these effects. The present findings suggest that PPC-CS micron fibers containing ChABC are a feasible option for spinal cord injury treatment. Furthermore, the system described here may be useful for local Delivery of other therapeutic agents.

  • Sustained Delivery of dbcamp by poly propylene carbonate micron fibers promotes axonal regenerative sprouting and functional recovery after spinal cord hemisection
    Brain Research, 2013
    Co-Authors: Shilei Ni, Xingang Li, Hongxu Qi, Jiangang Wang
    Abstract:

    This study describes the use of poly(propylene carbonate) (PPC) electrospun fibers as vehicle for the Sustained Delivery of dibutyryl cyclic adenosine monophosphate (dbcAMP) to the hemisected spinal cord. The dbcAMP and PPC were uniformly mixed with acetonitrile; then, electrospinning was used to generate micron fibers. The release of dbcAMP was assessed by ELISA in vitro. Our results showed that the encapsulation of dbcAMP in the fibers led to stable and prolonged release in vitro. The PPC micron fibers containing dbcAMP and the PPC micron fibers without dbcAMP were then implanted into the hemisected thoracic spinal cord, followed by testing of the functional recovery and immunohistochemistry. Compared with the control group, Sustained Delivery of dbcAMP promoted axonal regenerative sprouting and functional recovery and reduced glial scar formation, and the PPC micron fibers without dbcAMP did not have these effects. Our findings demonstrated the feasibility of using PPC electrospun fibers containing dbcAMP for spinal cord injury. The approach described here also will provide a platform for the potential Delivery of other axon-growth-promoting or scar-inhibiting agents.