Recent developments in poly(dopamine)-based coatings for biomedical applications.

The success of polymer coatings for biomedical applications is undeniable. Among the very successful examples are poly(dopamine) (PDA) films due to their simplicity in deposition and beneficial interaction with biomolecules and cells. The aim of this review is to highlight the findings and achievement of PDA in nanomedicine since 2011. We discuss the progress that has been made to elucidate the structure of PDA and novel aspects considering the assembly of PDA-based films on diverse substrates. We highlight the newest results considering the biological evaluation PDA-based coatings to control cell behavior and the use of PDA in biosensing. The popularity of PDA remains unchanged, but the research efforts start to be consolidated toward more specific aims and clinical applications.

Phospholipid-polymer amphiphile hybrid assemblies and their interaction with macrophages.

Recently, the combination of lipids and block copolymers has become an alternative to liposomes and polymersomes as nano-sized drug carriers. We synthesize novel block copolymers consisting of poly(cholesteryl acrylate) as the hydrophobic core and poly(N-isopropylacrylamide) (PNIPAAm) as the hydrophilic extensions. Their successful phospholipid-assisted assembly into vesicles is demonstrated using the evaporation-hydration method. The preserved thermo-responsive property of the lipid-polymer hybrids is shown by a temperature dependent adsorption behaviour of the vesicles to poly(l lysine) coated surfaces. As expected, the vesicle adsorption is found to be higher at elevated temperatures. The cellular uptake efficiency of hybrids is assessed using macrophages with applied shear stress. The amount of adhering macrophages is affected by the time and level of applied shear stress. Further, it is found that shorter PNIPAAm extensions lead to higher uptake of the assemblies by the macrophages with applied shear stress. No inherent cytotoxicity is observed at the tested conditions. Taken together, this first example of responsive lipid-polymer hybrids, and their positive biological evaluation makes them promising nano-sized drug carrier candidates.

Mixed poly(dopamine)/poly(L-lysine) (composite) coatings: from assembly to interaction with endothelial cells.

Engineered polymer films are of significant importance in the field of biomedicine. Poly(dopamine) (PDA) is becoming more and more a key player in this context. Herein, we deposited mixed films consisting of PDA and poly(L-lysine) (PLL) of different molecular weights. The coatings were characterized by quartz crystal microbalance with dissipation monitoring, atomic force microscopy, and X-ray photoelectron spectroscopy. The protein adsorption to the mixed films was found to decrease with increasing amounts of PLL. PDA/PLL capsules were also successfully assembled. Higher PLL content in the membranes reduced their thickness while the ζ-potential increased. Further, endothelial cell adhesion and proliferation over 96 h were found to be independent of the type of coating. Using PDA/PLL in liposome-containing composite coatings showed that sequential deposition of the layers yielded higher liposome trapping compared to one-step adsorption except for negatively charged liposomes. Association/uptake of fluorescent cargo by adherent endothelial cells was found to be different for PDA and PDA/PLL films. Taken together, our findings illustrate the potential of PDA/PLL mixed films as coatings for biomedical applications.

Liposomal drug deposits in poly(dopamine) coatings: effect of their composition, cell type, uptake pathway considerations, and shear stress.

Implantable devices equipped with coatings which have the ability to carry and deliver active compounds are of great interest. We report the assembly of liposome-containing poly(dopamine) films, and their interaction with adhering cells. The liposome composition is varied by adding lipophilic dopamine-conjugates and charged lipids. The cell mean fluorescence (CMF) of adhering cells due to the internalization of fluorescent cargo is found to be similar for coatings with the lipophilic-dopamine conjugates, while the charge affects the amount and location of the internalized cargo. The uptake mechanism for cargo by myoblasts using chemical inhibitors is found to be dependent on the used type of liposome. The CMF is significantly reduced for endothelial cells adhering to coatings with applied shear stress.

Liposome-containing polymer films and colloidal assemblies towards biomedical applications.

Liposomes are important components for biomedical applications. Their unique architecture and versatile nature have made them useful carriers for the delivery of therapeutic cargo. The scope of this minireview is to highlight recent developments of biomimetic liposome-based multicompartmentalized assemblies of polymer thin films and colloidal carriers, and to outline a selection of recent applications of these materials in bionanotechnology.

Recent progress of liposomes in nanomedicine.

Liposomes, spherical vesicles consisting of one or more lipid bilayer membrane(s) encapsulating an aqueous medium, are among the prominent players in the field of nanomedicine. Herein, we highlight the newest, atypical applications of liposomes towards their use in biomedicine. In particular, we put special emphasis on innovative chemical modification of liposomes, the interactions of liposomes with cells under the influence of shear stress, and the utilisation of liposomes as drug deposits in polymeric films and as components in synthetic cell mimics.

Liposomes as drug deposits in multilayered polymer films.

The ex vivo growth of implantable hepatic or cardiac tissue remains a challenge and novel approaches are highly sought after. We report an approach to use liposomes embedded within multilayered films as drug deposits to deliver active cargo to adherent cells. We verify and characterize the assembly of poly(l-lysine) (PLL)/alginate, PLL/poly(l-glutamic acid), PLL/poly(methacrylic acid) (PMA), and PLL/cholesterol-modified PMA (PMAc) films, and assess the myoblast and hepatocyte adhesion to these coatings using different numbers of polyelectrolyte layers. The assembly of liposome-containing multilayered coatings is monitored by QCM-D, and the films are visualized using microscopy. The myoblast and hepatocyte adhesion to these films using PLL/PMAc or poly(styrenesulfonate) (PSS)/poly(allyl amine hydrochloride) (PAH) as capping layers is evaluated. Finally, the uptake of fluorescent lipids from the surface by these cells is demonstrated and compared. The activity of this liposome-containing coating is confirmed for both cell lines by trapping the small cytotoxic compound thiocoraline within the liposomes. It is shown that the biological response depends on the number of capping layers, and is different for the two cell lines when the compound is delivered from the surface, while it is similar when administered from solution. Taken together, we demonstrate the potential of liposomes as drug deposits in multilayered films for surface-mediated drug delivery.

Cargo delivery to adhering myoblast cells from liposome-containing poly(dopamine) composite coatings.

Designing surfaces to deliver therapeutic compounds to adhering cells is of paramount importance for both implantable devices and tissue engineering. We report the assembly of composite films consisting of liposomes as drug deposits in a poly(dopamine) matrix. We monitor the film assembly using a quartz crystal microbalance with dissipation. We assess the response of adhering myoblast cells to these films containing fluorescent lipids in terms of uptake efficiency and cell mean fluorescence using flow cytometry. The viability of adhering myoblast cells, when the hydrophobic cytotoxic compound thiocoraline is entrapped in the lipid membrane, is assessed for different films. Coatings with one or two liposome deposition steps are considered. Further, the effect of the polymer separation layers between the liposome layers is determined. We found that it is possible to use the different nano-engineered composite coatings to impose a corresponding cellular response, e.g., a higher amount of embedded liposomes leads to higher uptake efficiency of the fluorescent lipids and cell mean fluorescence or a higher reduction in the viability of the adhering cells. Assessment of the uptake efficiency and cell mean fluorescence over time reveals a decrease in both parameters over 48 h. Our results demonstrate the ability to affect the cell response depending on the properties of the films, opening up a variety of opportunities for biomedical applications in substrate-mediated drug delivery.

Polydopamine--a nature-inspired polymer coating for biomedical science.

Polymer coatings are of central importance for many biomedical applications. In the past few years, poly(dopamine) (PDA) has attracted considerable interest for various types of biomedical applications. This feature article outlines the basic chemistry and material science regarding PDA and discusses its successful application from coatings for interfacing with cells, to drug delivery and biosensing. Although many questions remain open, the primary aim of this feature article is to illustrate the advent of PDA on its way to become a popular polymer for bioengineering purposes.

Polydopamine/liposome coatings and their interaction with myoblast cells.

Surface-mediated drug delivery is a recent concept, where active surface coatings are employed to deliver therapeutic cargo to cells. Herein, we explore the potential of liposomes embedded in polydopamine (PDA) coatings to serve as drug deposits stored on planar substrates. We quantify the PDA growth rate on glass by XPS and show that PDA coatings support myoblast adherence and proliferation. Further, PDA capping layers were deposited on glass substrates precoated with poly(L-lysine) and zwitterionic liposomes. Already thin PDA capping layers render liposome coated surfaces cell adhesive. We experimentally show for the first time, the internalization of a model hydrophobic cargo, that is, fluorescent lipids embedded within the lipid bilayer of liposomes by the cells from the surface. This is evident from the fluorescence exhibited by the cells grown on PDA coatings containing fluorescently labeled liposomes, with the highest fluorescent intensity found in the close proximity of the cell nuclei. The cargo uptake efficiency depends on the thickness of the PDA capping layer and the cell residence time on the coated substrates. Taken together, we demonstrate the first step toward the establishment of a versatile approach using liposomal drug deposits in polymer thin films for surface-mediated drug delivery.