Pulsatile protein release from a laminated device comprising of polyanhydrides and pH-sensitive complexes

Jiang, Hongliang; Zhu, K. J.

doi:10.1016/s0378-5173(99)00336-1

Cited by 45 publications

(13 citation statements)

References 28 publications

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“…Using surface eroding polymers such as polyanhydrides, this concept was further applied in 2000. 35,36 The polyanhydrides were incorporated as barriers to water, and as the polymer eroded the water starts dissolving the underlying drug depots, as depicted in Figure 1.3. Recently, a pair of groups studied 6,37 polyanhydride barrier systems to explain osteogenesis with various growth factors, demonstrating in vivo efficacy and sequential delivery of multiple drugs 38 .…”

Section: Bmpr: Existing Workmentioning

confidence: 99%

Barrier-Mediated Pulsatile Release

Gandhi

Gosse

Nishii

et al. 2015

Journal of Membrane Science

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ii To my loving wife and wonderful parents.iii ACKNOWLEDGMENTS First and foremost I would like to thank my research advisor Dr. Eric Nuxoll for his support, brilliant advice, professionalism and endless patience. He has been a great mentor throughout my doctoral studies at the University of Iowa since I became his first graduate student. Besides overall research skills, I learned much more including how to address a problem in a practical way, determine priorities and most importantly how to express and defend ideas. I have had the privilege to work with very talented undergrad students Matthew Gosse and Derek Baerenwald, who directly contributed to this project. I am also grateful to Yasuhiro Nishii, a visiting scholar from Japan, for his partial contributions to this work and continued work forward with this project. Guiding and mentoring these bright individuals was an exciting opportunity and also a great experience for me. Others who have helped me along the way include my fellow research group members Ann O'Toole, Joel Coffel, Erica Bader and Bryce Hundley. iv I am incredibly grateful to my parents who have always supported me. I have been blessed to be born in a loving family that has fully encouraged and enabled me to achieve my dreams. Finally, no words can express my thankfulness to Khushbu, my wife, who always stood by me throughout this journey. Without her encouragement and motivation I would not have pursued the education to the length I have.v ABSTRACT Solutes are often most efficiently deployed in discrete pulses, for example in the delivery of herbicides or drugs. Manual application of each pulse can be labor-intensive, automated application of each pulse can be capital intensive, and both are often costly and impractical. Barrier-Mediated Pulsatile Release (BMPR) systems offer a materialsbased alternative for automated pulsatile drug delivery, without pumps, power supplies, or complex circuitry. While earlier materials-based approaches such as delayed-release microcapsules are limited to two or three pulses due to the independent nature of each pulse's timing control, BMPR systems link the timing of each pulse to the previous pulse.Each dose of drug is sequestered in its own stimuli-sensitive depot, releasing only upon contact with the stimulant. These depots are stacked with sacrificial barriers in between, each of which block the stimulant for a predetermined time. For instance, layers of soluble drug may be separated by degradable polymer layers. Water, as the stimulant, will erode the polymer layer over a fixed period of time, followed by quick dissolution and release of the underlying drug and the start of degradation for the next polymer layer.This example, however, is quickly limited by irregular polymer erosion, a single stimulant (water), and difficulty in scaling delay times.The research work presented in this thesis reports the development of a generalized BMPR system which overcomes those limitations. Model drugs (methylene blue and methyl orange) were immobilized in a pH-sensitive ...

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Section: Bmpr: Existing Workmentioning

confidence: 99%

Barrier-Mediated Pulsatile Release

Gandhi

Gosse

Nishii

et al. 2015

Journal of Membrane Science

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“…A laminated device comprised of polyanhydrides as isolating layers and pH-sensitive complexes as protein-loaded layers was designed to deliver proteins like myoglobin and bovine serum albumin in a pulsatile manner. Poly(sebacic anhydride)-b-polyethylene glycol (PSA-b-PEG) and poly(trimellitylimidoglycine-co-sebacic anhydride)-b-polyethylene glycol (P(TMA-gly-co-SA)-b-PEG) were synthesized as isolating layers for their positive processing properties at room temperature and suitable erosion duration [ 128 ].…”

Section: Polyanhydridesmentioning

confidence: 99%

Biodegradable Polymers for Focal Delivery Systems

Khan¹,

Challa²,

Langer

et al. 2013

Advances in Delivery Science and Technology

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“…There is no current successful pulsatile system of PTH release, although a variety of delivery strategies have been explored for the pulsatile release of other agents from polymeric implants [14][15][16][17][18][19]. Based on the triggering mechanisms, they can be classified as stimulus-induced pulsatile release systems and self-regulated pulsatile release systems.…”

Section: Introductionmentioning

confidence: 99%

“…Critical considerations have to be given to the biocompatibility, biodegradability and toxicity of these stimulus-responsive polymeric systems. In self-regulated pulsatile release systems, drugs are usually encapsulated in one way or another within a barrier material, which is composed of an erodible or biodegradable polymer [19,31,32]. Depending on the barrier material structure and thickness, different release times can be achieved.…”

Section: Introductionmentioning

confidence: 99%

Pulsatile release of parathyroid hormone from an implantable delivery system

et al. 2007

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Intermittent (pulsatile) administration of parathyroid hormone (PTH) is known to improve bone micro-architecture, mineral density and strength. Therefore, daily injection of PTH has been clinically used for the treatment of osteoporosis. However, this regimen of administration is not convenient and is not a favorable choice of patients. In this study, an implantable delivery system has been developed to achieve pulsatile release of PTH. A well-defined cylindrical device was first fabricated with a biodegradable polymer, poly(lactic acid) (PLLA), using a reverse solid free form fabrication technique. Three-component polyanhydrides composed of sebacic acid, 1,3-bis(pcarboxyphenoxy) propane and poly(ethylene glycol) were synthesized and used as isolation layers. The polyanhydride isolation layers and PTH-loaded alginate layers were then stacked alternately within the delivery device. The gap between the stacked PTH-releasing core and the device frame was filled with PLLA to seal. Multi-pulse PTH release was achieved using the implantable device. The lag time between two adjacent pulses were modulated by the composition and the film thickness of the polyanhydride. The released PTH was demonstrated to be biologically active using an in vitro assay. Timed sequential release of multiple drugs has also been demonstrated. The implantable device holds promise for both systemic and local therapies.

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Pulsatile protein release from a laminated device comprising of polyanhydrides and pH-sensitive complexes

Cited by 45 publications

References 28 publications

Barrier-Mediated Pulsatile Release

Barrier-Mediated Pulsatile Release

Biodegradable Polymers for Focal Delivery Systems

Pulsatile release of parathyroid hormone from an implantable delivery system

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