Multilayer Nanoencapsulation. New Approach for Immune Protection of Human Pancreatic Islets

Abstract

Immune protection of artificial tissue by means of pancreatic islet microencapsulation is a very ambitious new approach to avoid life-long immune suppression. But the success in the utilization of the alginate-beads with incorporated islets is unfortunately limited. Some of the problems cannot be solved by a two-component system, so polymer encapsulation of the microbeads was tested to improve the properties. In the present paper a pure nanoencapsulation multilayer approach was tested in order to reduce the size of the capsule and possibly apply in the future a multilayer capsule with individual properties in each layer or region of the capsule. Different polycations were attached in a self-assembly process. The advantage in using the surface charge of islets as binding site for the polyions is the guarantee of complete coverage after the second layer. Release of insulin was determined to characterize the function of the islets after encapsulation as well as the permeability of the capsule. Fluorescence microscopy was used to visualize the polyelectrolyte layers. Finally by means of an immune assay, the protection capability of the capsule was proved. In these first measurements the encapsulation with a multilayer nanocapsule was shown to be a possible alternative to the more space-consuming and random islet-trapping microencapsulation.

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

“…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.…”

Encapsulation technologies in beta cell replacement therapies for Type 1 diabetes

“…Although alginate remains the most popular hydrogel of choice, agarose [115,116], chitosan [117], methacrylic acid [118], methyl methacrylate [119], polyamide [120,121], PVA [122], PEG [123,124], 2-hydroxyethyl methacrylate (HEMA) [125,126], AN69 (a copolymer of acrylonitrile and sodium-methallyl sulfonate) [127], and collagens type I and IV [128] are all being evaluated for use in islet and stem cell encapsulation. Stimuli-responsive synthetic hydrogels are commonly employed in cell encapsulation and tissue engineering.…”

Encapsulation and Surface Engineering of Pancreatic Islets: Advances and Challenges

“…The LBL represents a universal surface modification approach that allows for producing surface-attached films with controlled thickness, permeability, mechanical properties and surface chemistry. The technique has been recently applied to modify islet surfaces (Krol et al, 2006;. The LbL modification of islet surfaces is based on alternating deposition of water www.intechopen.com soluble polymers on surfaces from aqueous solutions which results in nano-thin coatings of controllable thickness and composition (Decher & Schlenoff, 2002;Kharlampieva & Sukhishvili, 2006;Tang et al, 2006).…”

“…Modification of the last coating layer can be used to support functionality of islets and reduce the immune response from a host system. The cutoff of the polyelectrolyte multilayer (PEM) is defined by polyelectrolytes used in coating formation (Krol et al, 2006).…”

“…However, this technology is limited to the introduction of specified functional small molecules to cells and might interfere with cell physiology (Rabuka et al, 2008;Paulick et al, 2007). Layer-by-layer (LbL) technique has been recently applied as a new approach to modify islet surfaces (Krol et al, 2006;. The technique is based on alternating LbL deposition of water soluble polymers on surfaces from aqueous solutions which results in nano-thin coatings of controllable thickness and composition (Decher & Schlenoff, 2002;Kharlampieva & Sukhishvili, 2006;Tang et al, 2006).…”