Tannic acid (TA)-based multilayer assemblies have attracted increasing interest for biomedical applications. Here we explore properties of TA-poly(N-vinylpyrrolidone) (TA-PVPON) hydrogen-bonded multilayers for drug encapsulation and long-term storage. We demonstrate that the small molecular weight anticancer drug, doxorubicin (DOX), can be successfully loaded into (TA-PVPON) capsules with high encapsulation efficiency. We have also found that the encapsulated DOX can be efficiently stored inside the capsules for the pH range from pH = 7.4 to pH = 5. We show that the chemical and functional stability of TA at neutral and basic pH values is achieved through complexation with PVPON. The UV-vis spectrophotometry and in situ ellipsometry analyses of the hydrogen bonding interactions between TA and PVPON at different pH values reveal pH-dependent behavior of TA-PVPON capsules for the pH range from pH = 7.4 to pH = 5. Increasing deposition pH value from pH = 5 to pH = 7.4 leads to a 2-fold decrease in capsule thickness. However, this trend is reversed when salt concentration of the deposition solutions is increased from 0.01 M to 0.1 M NaCl. We have also demonstrated that the permeability of (TA-PVPON) capsules prepared using low salt deposition conditions and pH = 7.4 can be increased 2-fold by exposure of the capsules to 0.1 M NaCl salt solutions at the same pH. Our work opens new perspectives for design of novel polymer carriers for controlled drug delivery in cancer therapy.

Though transplantation of pancreatic islet cells has emerged as a promising treatment for Type 1 diabetes its clinical application remains limited due to a number of limitations including both pathogenic innate and adaptive immune responses. We report here on a novel type of multifunctional cytoprotective material applied to coat living pancreatic islets. The coating utilizes hydrogen-bonded interactions of a natural polyphenol (tannic acid) with poly(N-vinylpyrrolidone) deposited on the islet surface via non-ionic layer-by-layer assembly. We demonstrate that the coating is conformal over the surface of mammalian islets including those derived from rat, non-human primate (NHP), and human. In contrast to unmodified controls, the coated islets maintain their viability and β-cell functionality for at least 96 hours in vitro. We also determine that the coating demonstrates immunomodulatory cytoprotective properties suppressing pro-inflammatory cytokine synthesis in stimulated bone marrow-derived macrophages and diabetogenic BDC-2.5 T cells. The coating material combines high chemical stability under physiologically relevant conditions with capability of suppressing cytokine synthesis, crucial parameters for prolonged islet integrity, viability, and function in vivo. Our study offers new opportunities in the area of advanced multifunctional materials to be used for a cell-based transplantation therapy.

We report on nanothin multilayer hydrogels of cross-linked poly(N-vinylcaprolactam) (PVCL) that exhibit distinctive and reversible thermoresponsive behavior. The single-component PVCL hydrogels were produced by selective cross-linking of PVCL in layer-by-layer films of PVCL-NH2 copolymers assembled with poly(methacrylic acid) (PMAA) via hydrogen bonding. The degree of the PVCL hydrogel film shrinkage, defined as the ratio of wet thicknesses at 25°C to 50°C, was demonstrated to be 1.9±0.1 and 1.3±0.1 for the films made from PVCL-NH2-7 and PVCL-NH2-14 copolymers, respectively. No temperature-responsive behavior was observed for non-cross-linked two-component films due to the presence of PMAA. We also demonstrated that temperature-sensitive PVCL capsules of cubical and spherical shapes could be fabricated as hollow hydrogel replicas of inorganic templates. The cubical (PVCL)7 capsules retained their cubical shape when temperature was elevated from 25°C to 50°C exhibiting 21±1% decrease in the capsule size. Spherical hydrogel capsules demonstrated similar shrinkage of 23±1%. The temperature-triggered capsule size changes were completely reversible. Our work opens new prospects for developing biocompatible and nanothin hydrogel-based coatings and containers for temperate-regulating drug delivery, cellular uptake, sensing, and transport behavior in microfluidic devices.

We have tailored the internal architecture of ultrathin poly(methacrylic acid) (PMAA) hydrogels from well stratified to highly intermixed by controlling the internal structure in layer-by-layer templates used for hydrogel fabrication. We have found pH-triggered swelling properties of these hydrogels to be significantly affected by hydrogel architecture. Well-stratified hydrogels exhibited a dramatic 10-fold increase in thickness when transitioned between pH = 5 and 7.5, unlike the 2-fold swelling observed in less-organized hydrogels.