Layer-by-Layer Assembly of a Conformal Nanothin PEG Coating for Intraportal Islet Transplantation

Wilson, John T.; Cui, Wanxing; Chaikof, Elliot L.

doi:10.1021/nl080694q

Cited by 185 publications

(209 citation statements)

References 67 publications

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“…3,10 Further, the ability of multilayers to be built from biocompatible and bioresorbable polyelectrolytes has led to additional applications, including modification of cell adhesion on surfaces, 11 tissue-and skin-bonding films, 12 coatings directly applied to epithelial or endothelial cell layers in situ 13,14 , or even coatings on living single cells. [15][16][17] In concert with a growing interest in applying multilayers to biomedical applications, erodible multilayers that deconstruct in aqueous conditions via disassembly and/or breakdown of the constituent polymers have begun to be explored as potential controlled release drug delivery films. [18][19][20][21] Drug-loaded degradable multilayers have been explored for the sustained release of small-molecule antibiotics, protein therapeutics, or plasmid DNA.…”

mentioning

confidence: 99%

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

Su¹,

Kim²,

Kim³

et al. 2009

ACS Nano

155

120

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We describe protein-and oligonucleotide-loaded layer-by-layer (LbL)-assembled multiplayer films incorporating a hydrolytically degradable polymer for transcutaneous drug or vaccine delivery. Films were constructed based on electrostatic interactions between a cationic poly(β-amino ester) (denoted Poly-1) with a model protein antigen, ovalbumin (ova), and/or immunostimulatory CpG (Cytosine-phosphate diester-Guanine rich) DNA oligonucleotide adjuvant molecules. Linear growth of nanoscale Poly-1/ova bilayers was observed. Dried ova protein-loaded films rapidly deconstructed when rehydrated in saline solutions, releasing ova as non-aggregated/non-degraded protein, suggesting that the structure of biomolecules integrated into these multilayer films are preserved during release. Using confocal fluorescence microscopy and an in vivo murine ear skin model, we demonstrated delivery of ova from LbL films into barrierdisrupted skin, uptake of the protein by skin-resident antigen-presenting cells (Langerhans cells), and transport of the antigen to the skin-draining lymph nodes. Dual incorporation of ova and CpG oligonucleotides into the nanolayers of LbL films enabled dual release of the antigen and adjuvant with distinct kinetics for each component; ova was rapidly released while CpG was released in a relatively sustained manner. Applied as skin patches, these films delivered ova and CpG to Langerhans Cells in the skin. To our knowledge, this is the first demonstration of LbL films applied for the delivery of biomolecules into skin. This approach provides a new route for storage of vaccines and other immunotherapeutics in a solid-state thin film for subsequent delivery into the immunologically-rich milieu of the skin.

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mentioning

confidence: 99%

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

Su¹,

Kim²,

Kim³

et al. 2009

ACS Nano

155

120

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“…16 In addition to these hydrodynamics-based methods, other conformal coating techniques that involve surface chemistry include interfacial polymerization, 17 surface binding with polymer-lipid, 18,19 and layer-bylayer poly(L-lysine)(PLL)-PEG copolymer assembly. 20 Magnetic conformal coating by Khademhosseini et al 3 uses a magnetic force to pull cell aggregates that have a magnetic core through polymer layers in a syringe tube. With this magnetic method, the authors are able to conformally coat agarose-immobolized cell aggregates with a coating layer thickness of less than 70 lm.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic conformal coating of non-spherical magnetic particles

et al. 2014

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We present the conformal coating of non-spherical magnetic particles in a colaminar flow microfluidic system. Whereas in the previous reports spherical particles had been coated with thin films that formed spheres around the particles; in this article, we show the coating of non-spherical particles with coating layers that are approximately uniform in thickness. The novelty of our work is that while liquid-liquid interfacial tension tends to minimize the surface area of interfacesfor example, to form spherical droplets that encapsulate spherical particles-in our experiments, the thin film that coats non-spherical particles has a non-minimal interfacial area. We first make bullet-shaped magnetic microparticles using a stopflow lithography method that was previously demonstrated. We then suspend the bullet-shaped microparticles in an aqueous solution and flow the particle suspension with a co-flow of a non-aqueous mixture. A magnetic field gradient from a permanent magnet pulls the microparticles in the transverse direction to the fluid flow, until the particles reach the interface between the immiscible fluids. We observe that upon crossing the oil-water interface, the microparticles become coated by a thin film of the aqueous fluid. When we increase the two-fluid interfacial tension by reducing surfactant concentration, we observe that the particles become trapped at the interface, and we use this observation to extract an approximate magnetic susceptibility of the manufactured non-spherical microparticles. Finally, using fluorescence imaging, we confirm the uniformity of the thin film coating along the entire curved surface of the bullet-shaped particles. To the best of our knowledge, this is the first demonstration of conformal coating of non-spherical particles using microfluidics. V C 2014 AIP Publishing LLC. [http://dx

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“…Several methods of conformal coating have been developed recently, including covalent surface attachment of polyethylene glycol (PEG), known as 'PEGylation' [18], and layer-by-layer encapsulation [19][20][21][22][23][24][25][26][27][28]. Nano-layers with different combinations of components, including streptavidin and biotin-PEG derivatives [19,24], complement receptor 1 and heparin [25], and PEG-lipid and poly(vinyl alcohol) [26,27], have been previously researched as islet surface coatings.…”

Section: Introductionmentioning

confidence: 99%

“…Nano-layers with different combinations of components, including streptavidin and biotin-PEG derivatives [19,24], complement receptor 1 and heparin [25], and PEG-lipid and poly(vinyl alcohol) [26,27], have been previously researched as islet surface coatings. Most of these attempts at islet encapsulation have focused on development of the method, with relatively little emphasis on in vivo evaluation of the technology, and particularly on the maintenance of functional beta cells in an allogeneic environment.…”

Section: Introductionmentioning

confidence: 99%

“…Teramura and Iwata demonstrated that coating of islet surfaces with PEG-lipid and urokinase could effectively protect against blood-mediated inflammatory reactions in a syngeneic mouse model of transplantation [23]. However, a recent study using conformal coating to encapsulate islets via layer-by-layer deposition of poly(L-lysine)-g-PEG-(biotin) and streptavidin failed to show any improvement in the survival and function of the implanted allo-islets [19]. Effective immunoprotection using nano-coating thus remains a challenge in islet transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Nano-scale encapsulation enhances allograft survival and function of islets transplanted in a mouse model of diabetes

et al. 2012

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Aims/hypothesis The success of islet transplantation as a treatment for type 1 diabetes is currently hampered by post-transplantation loss of functional islets through adverse immune and non-immune reactions. We aimed to test whether early islet loss can be limited and transplant survival improved by the application of conformal nano-coating layers to islets. Methods Our novel coating protocol used alternate layers of phosphorylcholine-derived polysaccharides (chitosan or chondroitin-4-sulphate) and alginate as coating materials, with the binding based on electrostatic complexation. The in vitro function of encapsulated mouse islets was studied by analysing islet secretory function and cell viability. The in vivo function was evaluated using syngeneic and allogeneic transplantation in the streptozotocin-induced mouse model of diabetes. Results Nano-scale encapsulated islets retained appropriate islet secretory function in vitro and were less susceptible to complement-and cytokine-induced apoptosis than nonencapsulated control islets. In in vivo experiments using a syngeneic mouse transplantation model, no deleterious responses to the coatings were observed in host animals, and the encapsulated islet grafts were effective in reversing hyperglycaemia. Allo-transplantation of the nano-coated islets resulted in preserved islet function post-implantation in five of seven mice throughout the 1 month monitoring period. Conclusions/interpretation Nano-scale encapsulation offers localised immune protection for implanted islets, and may be able to limit early allograft loss and extend survival of transplanted islets. This versatile coating scheme has the potential to be integrated with tolerance induction mechanisms, thereby achieving long-term success in islet transplantation.

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Layer-by-Layer Assembly of a Conformal Nanothin PEG Coating for Intraportal Islet Transplantation

Cited by 185 publications

References 67 publications

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

Microfluidic conformal coating of non-spherical magnetic particles

Nano-scale encapsulation enhances allograft survival and function of islets transplanted in a mouse model of diabetes

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