Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films

Hsu, Bryan B.; Jamieson, Kelsey S.; Hagerman, Samantha R.; Holler, Eggehard; Ljubimova, Julia Y.; Hammond, Paula T.

doi:10.1002/anie.201403702

Cited by 27 publications

(24 citation statements)

References 83 publications

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“…These polyelectrolyte multilayers, PEMUs, are dense, conformal coatings of the same material as a PEC . The polyelectrolytes are combined in a stoichiometric proportion, or they are non‐stoichiometric, depending on the polymers, the deposition conditions, and even the thickness of the film . PEC films of tunable composition were also obtained by deposition of PEC nanoparticles…”

Section: Introductionmentioning

confidence: 99%

Saloplastics: Processing Compact Polyelectrolyte Complexes

2015

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Polyelectrolyte complexes (PECs) are prepared by mixing solutions of oppositely charged polyelectrolytes. These diffuse, amorphous precipitates may be compacted into dense materials, CoPECs, by ultracentrifugation (ucPECs) or extrusion (exPECs). The presence of salt water is essential in plasticizing PECs to allow them to be reformed and fused. When hydrated, CoPECs are versatile, rugged, biocompatible, elastic materials with applications including bioinspired materials, supports for enzymes and (nano)composites. In this review, various methods for making CoPECs are described, as well as fundamental responses of CoPEC mechanical properties to salt concentration. Possible applications as synthetic cartilage, enzymatically active biocomposites, self-healing materials, and magnetic nanocomposites are presented.

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Section: Introductionmentioning

confidence: 99%

Saloplastics: Processing Compact Polyelectrolyte Complexes

2015

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“…Compared to polymers, less charge dense materials like proteins may not readily incorporate into electrostatically assembled LbL unless they are sufficiently charged. At pH 5, lysozyme has an isoelectric point of 11, and a net charge of +10, which was found to enable significant loading into LbL films …”

Section: Resultsmentioning

confidence: 99%

Rapid and efficient sprayed multilayer films for controlled drug delivery

Hsu

Hagerman

Hammond

2016

J of Applied Polymer Sci

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ABSTRACT:The speed and scalability of film fabrication can dictate the translation of technologies from the laboratory scale to industrial level mass production. Spray-assisted layer-by-layer (LbL) film assembly enables the rapid coating of geometrically complex and porous substrates with functional polyelectrolyte multilayers. Unfortunately, the encapsulation efficiency can be as low as one percent, making this technique prohibitively costly with even modestly priced materials. Herein, we used containment chambers to separately capture the aerosolized solutions for each step in the spray-LbL process and analyzed the effect of recycling on multilayer film assembly. With potential biomedical applications, we studied the controlled release films of (Poly 2/heparin/lysozyme/heparin) n films and tracked the distribution of lysozyme after film assembly. In a "Conventional" Spray-LbL protocol, only 6% of the aerosolized lysozyme is incorporated into the film. By collecting and returning the expended solutions to their respective reservoirs (Recycle SprayLbL), we increased this efficiency to 15%. We also tuned the final distribution of lysozyme by adjusting the spray times (Optimized Spray-LbL), which minimized the amount of lysozyme lost to non-specific adsorption and reduced the fraction of lysozyme lost to the wash step from 30% and 75% (Conventional and Recycle Spray-LbL, respectively) to 13%. Despite the changes in film assembly parameters, each film demonstrated similar controlled release properties. With the inherent limitations of time and cost facing Dip and Conventional Spray-LbL technologies, respectively, the implementation of recycling to the latter demonstrates improvements in efficiency and time that may make it more attractive for the manufacture of biomedical coatings.

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“…[2] In order to deliver multiple signal molecules in a desired sequence, researchers have attempted to develop delivery vehicles with spatiotemporal control by trapping proteins within degradable polymers such as poly(lactide-co-glycolic acid), poly(ε-caprolactone), and hydrogels. Representative examples include the composite films made by the layer-by-layer assembly of proteins and polymers, [3] as well as the composite scaffolds made by electrospinning [4] or by fusing polymer particles that contain desired proteins using organic vapor or high-pressure CO 2 . [5] For the composite films, the sequential release of the proteins is achieved through a hydrolysable barrier that separates layers of first protein from the subsequent ones; after releasing the first protein, the hydrolysis of the barrier allows for the release of the subsequent proteins.…”

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confidence: 99%

Enzyme‐Responsive Delivery of Multiple Proteins with Spatiotemporal Control

et al. 2015

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The growth of tissues and organs is regulated by orchestrated signals from biomolecules such as enzymes and growth factors. The ability to deliver signal molecules in response to particular biological events (e.g., enzyme expression and activation) holds great promise towards tissue healing and regeneration. The current delivery vehicles mainly rely on hydrolysable scaffolds and thin films of protein-containing polymers, which cannot be programmed to respond to biological signals. We report herein an injectable delivery platform based on enantiomeric protein nanocapsules, which can deliver multiple proteins with spatiotemporal control in response to the tissue proteases secreted during wound healing. Exemplified by stroke and diabetic wound healing in mice, sequential delivery of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) greatly enhances tissue revascularization and vessel maturation, providing effective delivery vehicles for tissue engineering and reparative medicine.

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Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films

Cited by 27 publications

References 83 publications

Saloplastics: Processing Compact Polyelectrolyte Complexes

Saloplastics: Processing Compact Polyelectrolyte Complexes

Rapid and efficient sprayed multilayer films for controlled drug delivery

Enzyme‐Responsive Delivery of Multiple Proteins with Spatiotemporal Control

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