The Experts below are selected from a list of 222 Experts worldwide ranked by ideXlab platform
Patrick F Kiser - One of the best experts on this subject based on the ideXlab platform.
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design of a Drug eluting subcutaneous implant of the antiretroviral tenofovir alafenamide fumarate
Pharmaceutical Research, 2020Co-Authors: Solange M Simpson, Lakmini Widanapathirana, Samuel Sung, David Watrous, Jiang Qiu, Elizabeth Pearson, Alex Evanoff, Dipu Karunakaran, Jorge E Chacon, Patrick F KiserAbstract:Sexual transmission of HIV has been clinically proven to be preventable with a once-daily oral tablet; however, missed doses dramatically increase the risk of HIV infection. Long-Acting subcutaneous implants do not allow the user to miss a dose. A desirable Long-Acting Drug-eluting implant can deliver a constant amount of Drug, adjust the delivered dose, and be readily manufactured. We present a Long-Acting, subcutaneous implant design composed of tenofovir alafenamide hemifumarate (TAF) pellets loaded in a sealed polyether urethane tube for the prevention of HIV transmission. Implants were prepared with pressed Drug pellets and extruded polyurethane tubing. In vitro release rate of implants using different pellet formulations, rate-controlling membranes, and geometries were measured. Tenofovir alafenamide release appeared to be governed by a pseudo-steady state and followed a mass transport model of release from a cylindrical Drug reservoir. Implant seal integrity was tested and confirmed using mechanical testing. The inclusion of sodium chloride in the pellet increased the release rate and reduced initial lag. The release was sustained for 100 days. The release rate of tenofovir alafenamide mechanistically varied with geometry and rate controlling membrane composition. The polyether urethane implant presented herein is modular and tunable to adjust the release rate and duration of the TAF release.
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Design of a Drug-Eluting Subcutaneous Implant of the Antiretroviral Tenofovir Alafenamide Fumarate
Pharmaceutical Research, 2020Co-Authors: Solange M Simpson, Lakmini Widanapathirana, Samuel Sung, David Watrous, Jiang Qiu, Elizabeth Pearson, Alex Evanoff, Dipu Karunakaran, Jorge E Chacon, Patrick F KiserAbstract:Purpose Sexual transmission of HIV has been clinically proven to be preventable with a once-daily oral tablet; however, missed doses dramatically increase the risk of HIV infection. Long-Acting subcutaneous implants do not allow the user to miss a dose. A desirable Long-Acting Drug-eluting implant can deliver a constant amount of Drug, adjust the delivered dose, and be readily manufactured. We present a Long-Acting, subcutaneous implant design composed of tenofovir alafenamide hemifumarate (TAF) pellets loaded in a sealed polyether urethane tube for the prevention of HIV transmission. Methods Implants were prepared with pressed Drug pellets and extruded polyurethane tubing. In vitro release rate of implants using different pellet formulations, rate-controlling membranes, and geometries were measured. Results Tenofovir alafenamide release appeared to be governed by a pseudo-steady state and followed a mass transport model of release from a cylindrical Drug reservoir. Implant seal integrity was tested and confirmed using mechanical testing. The inclusion of sodium chloride in the pellet increased the release rate and reduced initial lag. The release was sustained for 100 days. Conclusions The release rate of tenofovir alafenamide mechanistically varied with geometry and rate controlling membrane composition. The polyether urethane implant presented herein is modular and tunable to adjust the release rate and duration of the TAF release.
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Engineering a segmented dual-reservoir polyurethane intravaginal ring for simultaneous prevention of HIV transmission and unwanted pregnancy. PLoS One 2014
2016Co-Authors: Justin T. Clark, Meredith R. Clark, Namdev B. Shelke, Todd J. Johnson, Eric M. Smith, Andrew K. Andreasen, Joel S. Nebeker, Judit Fabian, David R. Friend, Patrick F KiserAbstract:The HIV/AIDS pandemic and its impact on women prompt the investigation of prevention strategies to interrupt sexual transmission of HIV. Long-Acting Drug delivery systems that simultaneously protect womenfrom sexual transmission of HIV and unwanted pregnancy could be important tools in combating the pandemic. We describe the design, in silico, in vitro and in vivo evaluation of a dual-reservoir intravaginal ring that delivers the HIV-1 reverse transcriptase inhibitor tenofovir and the contraceptive levonorgestrel for 90 days. Two polyether urethanes with two different hard segment volume fractions were used to make coaxial extruded reservoir segments with a 100 mm thick rate controlling membrane and a diameter of 5.5 mm that contain 1.3 wt % levonorgestrel. A new mechanistic diffusion model accurately described the levonorgestrel burst release in early time points and pseudo-steady state behavior at later time points. As previously described, tenofovir was formulated as a glycerol paste and filled into a hydrophilic polyurethane, hollow tube reservoir that was melt-sealed by induction welding. These tenofovir-eluting segments and 2 cm Long coaxially extruded levonorgestrel eluting segments were joined by induction welding to form rings that released an average of 7.5 mg tenofovir and 21 mg levonorgestrel per day in vitro for 90 days. Levonorgestrel segments placed intravaginally in rabbits resulted in sustained, dose-dependent levels of levonorgestrel in plasma and cervical tissue for 90 days. Polyurethane caps placed between segments successfully prevented diffusion of levonorgestrel into the tenofovir-releasing segment during storage.Hydrate
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engineering a segmented dual reservoir polyurethane intravaginal ring for simultaneous prevention of hiv transmission and unwanted pregnancy
PLOS ONE, 2014Co-Authors: Justin T. Clark, Meredith R. Clark, Namdev B. Shelke, Todd J. Johnson, Andrew K. Andreasen, Joel S. Nebeker, Judit Fabian, David R. Friend, Eric Smith, Patrick F KiserAbstract:The HIV/AIDS pandemic and its impact on women prompt the investigation of prevention strategies to interrupt sexual transmission of HIV. Long-Acting Drug delivery systems that simultaneously protect womenfrom sexual transmission of HIV and unwanted pregnancy could be important tools in combating the pandemic. We describe the design, in silico, in vitro and in vivo evaluation of a dual-reservoir intravaginal ring that delivers the HIV-1 reverse transcriptase inhibitor tenofovir and the contraceptive levonorgestrel for 90 days. Two polyether urethanes with two different hard segment volume fractions were used to make coaxial extruded reservoir segments with a 100 µm thick rate controlling membrane and a diameter of 5.5 mm that contain 1.3 wt% levonorgestrel. A new mechanistic diffusion model accurately described the levonorgestrel burst release in early time points and pseudo-steady state behavior at later time points. As previously described, tenofovir was formulated as a glycerol paste and filled into a hydrophilic polyurethane, hollow tube reservoir that was melt-sealed by induction welding. These tenofovir-eluting segments and 2 cm Long coaxially extruded levonorgestrel eluting segments were joined by induction welding to form rings that released an average of 7.5 mg tenofovir and 21 µg levonorgestrel per day in vitro for 90 days. Levonorgestrel segments placed intravaginally in rabbits resulted in sustained, dose-dependent levels of levonorgestrel in plasma and cervical tissue for 90 days. Polyurethane caps placed between segments successfully prevented diffusion of levonorgestrel into the tenofovir-releasing segment during storage.Hydrated rings endured between 152 N and 354 N tensile load before failure during uniaxial extension testing. In summary, this system represents a significant advance in vaginal Drug delivery technology, and is the first in a new class of Long-Acting multipurpose prevention Drug delivery systems.
Erica Schlesinger - One of the best experts on this subject based on the ideXlab platform.
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A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis
Pharmaceutical Research, 2016Co-Authors: Erica Schlesinger, Daniel Johengen, Ellen Luecke, Ian Mcgowan, Ariane Van Der Straten, Ginger Rothrock, Tejal DesaiAbstract:Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by Long Acting Drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP. Methods A thin-film polycaprolactone (PCL) membrane controls Drug release from a reservoir. To achieve membrane controlled release, TAF requires a formulation excipient such as PEG300 to increase the dissolution rate and reservoir solubility. Short-term In vitro release studies are used to develop an empirical design model, which is applied to the production of in vitro prototype devices demonstrating up to 90-days of linear release and TAF chemical stability. Results The size and shape of the TFPD are tunable, achieving release rates ranging from 0.5 to 4.4 mg/day in devices no larger than a contraceptive implant. Based on published data for oral TAF, subcutaneous constant-rate release for HIV PrEP is estimated at 8-fold range.
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A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis
Pharmaceutical Research, 2016Co-Authors: Erica Schlesinger, Daniel Johengen, Ellen Luecke, Ginger D. Rothrock, Ian Mcgowan, Ariane Van Der Straten, Tejal A. DesaiAbstract:Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by Long Acting Drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP.
Tejal Desai - One of the best experts on this subject based on the ideXlab platform.
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A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis
Pharmaceutical Research, 2016Co-Authors: Erica Schlesinger, Daniel Johengen, Ellen Luecke, Ian Mcgowan, Ariane Van Der Straten, Ginger Rothrock, Tejal DesaiAbstract:Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by Long Acting Drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP. Methods A thin-film polycaprolactone (PCL) membrane controls Drug release from a reservoir. To achieve membrane controlled release, TAF requires a formulation excipient such as PEG300 to increase the dissolution rate and reservoir solubility. Short-term In vitro release studies are used to develop an empirical design model, which is applied to the production of in vitro prototype devices demonstrating up to 90-days of linear release and TAF chemical stability. Results The size and shape of the TFPD are tunable, achieving release rates ranging from 0.5 to 4.4 mg/day in devices no larger than a contraceptive implant. Based on published data for oral TAF, subcutaneous constant-rate release for HIV PrEP is estimated at 8-fold range.
Tejal A. Desai - One of the best experts on this subject based on the ideXlab platform.
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A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis
Pharmaceutical Research, 2016Co-Authors: Erica Schlesinger, Daniel Johengen, Ellen Luecke, Ginger D. Rothrock, Ian Mcgowan, Ariane Van Der Straten, Tejal A. DesaiAbstract:Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by Long Acting Drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP.
Daniel Johengen - One of the best experts on this subject based on the ideXlab platform.
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A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis
Pharmaceutical Research, 2016Co-Authors: Erica Schlesinger, Daniel Johengen, Ellen Luecke, Ian Mcgowan, Ariane Van Der Straten, Ginger Rothrock, Tejal DesaiAbstract:Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by Long Acting Drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP. Methods A thin-film polycaprolactone (PCL) membrane controls Drug release from a reservoir. To achieve membrane controlled release, TAF requires a formulation excipient such as PEG300 to increase the dissolution rate and reservoir solubility. Short-term In vitro release studies are used to develop an empirical design model, which is applied to the production of in vitro prototype devices demonstrating up to 90-days of linear release and TAF chemical stability. Results The size and shape of the TFPD are tunable, achieving release rates ranging from 0.5 to 4.4 mg/day in devices no larger than a contraceptive implant. Based on published data for oral TAF, subcutaneous constant-rate release for HIV PrEP is estimated at 8-fold range.
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A Tunable, Biodegradable, Thin-Film Polymer Device as a Long-Acting Implant Delivering Tenofovir Alafenamide Fumarate for HIV Pre-exposure Prophylaxis
Pharmaceutical Research, 2016Co-Authors: Erica Schlesinger, Daniel Johengen, Ellen Luecke, Ginger D. Rothrock, Ian Mcgowan, Ariane Van Der Straten, Tejal A. DesaiAbstract:Purpose The effectiveness of Tenofovir based HIV pre-exposure prophylaxis (PrEP) is proven, but hinges on correct and consistent use. User compliance and therapeutic effectiveness can be improved by Long Acting Drug delivery systems. Here we describe a thin-film polymer device (TFPD) as a biodegradable subcutaneous implant for PrEP.
