Mechanistic studies of an autonomously pulsing hydrogel/enzyme system for rhythmic hormone delivery

Bhalla, Amardeep S.; Siegel, Ronald A.

doi:10.1016/j.jconrel.2014.10.019

Cited by 19 publications

(15 citation statements)

References 60 publications

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“…In this context, the proximity of NIPA’s LCST to human body temperature (37 °C) has made this polymer of particular interest in drug delivery 45 . For example, a number of groups have demonstrated pulsatile release of drugs from thermosensitive NIPA gels through temperature control 29 – 31 . Inspired by these past studies, we investigated whether the multilayer structure of our capsules could make them interesting candidates for drug delivery.…”

Section: Resultsmentioning

confidence: 99%

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Onion-like multilayered polymer capsules synthesized by a bioinspired inside-out technique

Zarket

Raghavan

2017

Nat Commun

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Diverse structures in nature, such as the spinal disc and the onion have many concentric layers, and are created starting from the core and proceeding outwards. Here, we demonstrate an inside-out technique for creating multilayered polymer capsules. First, an initiator-loaded gel core is placed in a solution of monomer 1. The initiator diffuses outward and induces polymerization, leading to a shell of polymer 1. Thereafter, the core-shell structure is loaded with fresh initiator and placed in monomer 2, which causes a concentric shell of polymer 2 to form around the first shell. This process can be repeated to form multiple layers, each of a distinct polymer, and of controlled layer thickness. We show that these multilayered capsules can exhibit remarkable mechanical resilience as well as stimuli-responsive properties. The release of solutes from these capsules can be tailored to follow specific profiles depending on the chemistry and order of adjacent layers.

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Section: Resultsmentioning

confidence: 99%

“…pH or temperature. Solute release from such responsive capsules is shown to follow step-like (pulsatile) profiles, which suggests their potential utility in delivery applications 29 – 31 . More generally, our strategy can be used to create new multifunctional materials that mimic the remarkable structures found in nature.…”

Section: Introductionmentioning

confidence: 98%

Onion-like multilayered polymer capsules synthesized by a bioinspired inside-out technique

Zarket

Raghavan

2017

Nat Commun

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“…Recently the interest in controlled drug release also has increased enormously often requiring the degradation of the carrier matrix [1,2]. Since several enzymes have their optimum conditions close to, or even exactly at those prevailing in the human body [1][2][3][4], the enzyme catalyzed degradation of the carrier polymer is a convenient way to achieve controlled release. The approach has been used already to develop carrier matrices, which release the entrapped drug in this way [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

The role of enzyme adsorption in the enzymatic degradation of an aliphatic polyester

Polyák

Urban

Nagy

et al. 2019

Enzyme and Microbial Technology

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The enzyme catalyzed degradation of poly(3-hydroxybutyrate) (PHB) is a two-step process consisting of the adsorption of the enzyme on the surface of a PHB substrate and the cleavage of ester bonds. A deactivated enzyme was prepared by point mutagenesis to separate the two steps from each other. Measurements carried out with active and inactive enzymes on PHB particles proved that mutagenesis was successful and the modified enzyme did not catalyze degradation. Based on the Michaelis-Menten approach a kinetic model was proposed which could describe the processes quantitatively, the agreement between prediction and the measured data was excellent. The separation of the two processes allowed the determination of the adsorption kinetics of the enzyme; the rate constants of the adsorption and desorption process were determined for the first time. Comparison of these constants to reaction rates showed that adsorption is not instantaneous and can be the ratedetermining step. The area occupied by an enzyme molecule was also determined (13.1 nm 2) and it was found to be smaller than the value published in the literature (178 nm 2). The separation of the two steps makes possible the prediction and control of the degradation process.

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“…Pulsatile solute delivery is important to many fields, most notably medical applications such as hormone therapies (Bhalla and Siegel, 2014;Brabant et al, 1992;Hayes and Crowley, 1998), vaccines(Centers for Disease and Prevention, 2009;Walters et al, 2015), cancer therapies (Innominato et al, 2014;Lévi et al, 1997), and allergy treatments (Li et al, 2003), as well as for drugs where tolerance development is a concern, such as opiates (McKim, 2007) or nitroglycerin (Abrams, 1988). The ability to sequentially deliver multiple chemicals in a single administration, as well as minimize overall chemical consumption, also motivate the development of pulsatile delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Non-delaminating pulsatile release composites

Gandhi

Nuxoll

2016

Chemical Engineering Science

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By sequestering individual doses of chemical in stimuli-sensitive depot membranes and stacking them between stimulant barriers, automated pulsatile chemical release can be obtained from a simple polymer laminate. By using non-degrading hydrogel depots, this approach has been demonstrated releasing multiple chemicals in up to ten pulses, with each depot membrane delaminating and releasing its payload at a preprogrammed time. This paper reports the first experimental demonstration of a non-delaminating, non-degrading pulsatile release composite, for applications where delamination may be unsuitable. Non-delaminating systems not only require significantly larger development resources, they have an inherent periodicity limit which increases with the number of pulses desired. This limit is not analytically tractable, prompting the development of a computational model to predict the complete release profile. This model is validated against experimental delaminating systems, then adapted to nondelaminating systems to correlate the system's pulsatility with the physical parameters of the system, including diffusion coefficients, stimulant concentration, solute loading, scavenger loading and membrane thicknesses. These correlations facilitate rapid feasibility assessment of proposed non-delaminating pulsatile release applications prior to development of physical systems.

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Mechanistic studies of an autonomously pulsing hydrogel/enzyme system for rhythmic hormone delivery

Cited by 19 publications

References 60 publications

Onion-like multilayered polymer capsules synthesized by a bioinspired inside-out technique

Onion-like multilayered polymer capsules synthesized by a bioinspired inside-out technique

The role of enzyme adsorption in the enzymatic degradation of an aliphatic polyester

Non-delaminating pulsatile release composites

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