Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles.biomimetic ͉ drug delivery ͉ erythrocyte ͉ imaging ͉ nanotechnology

The in vitro uptake of core-shell nanoparticles encapsulated in a bio-macromolecular nanoshell assembled from multilayered polyelectrolytes was studied. Sulfate modified fluorescent polystyrene nanobeads (diameter 200 nm) were used as a solid core upon which charged multilayers of poly-l-lysine, chitosan, and heparin sulfate are electrostatically deposited utilizing a layer-by-layer (LbL) self-assembly process. The nanoshell composed of the multilayered polyelectrolytes was modified with poly(ethylene glycol) (PEG) of varying molecular weights (either MW 2000, 5000, or 20 000 Da) to form a hydrophilic and long-circulating nanoparticle. The assembly of the nanoshell was confirmed by zeta potential, transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The reversal in charge upon the deposition of alternating polyelectrolytes was observed by zeta potential measurements. The nanometer thickness of the nanoshell was confirmed by TEM. The presence of the (C-C-O)(n)() backbone in PEG at the surface of the nanoshell was confirmed by the increase in (C-O,N) peak area concentrations compared to (C-C) peak area, and these results were gathered from XPS. In vitro studies between suspension macrophages and core-shell nanoparticles were performed to determine how the hydrophilicity and the charge on the nanoshell can promote or reduce uptake. Results showed that after 24 h uptake was decreased 3-fold when PEGs of 2000 and 20 000 Da were chemisorbed to the nanoshell, as opposed to a nanoshell with either a positive or highly negative charge. Confocal microscopy aided in verifying that core-shell nanoparticles were internalized within the cell cytoplasm and were not attached to the cell surface. Protein adhesion studies with bovine serum albumin were performed to determine the relationship between surface charge and opsonization of core-shell nanoparticles. It was found that a hydrophilic surface with a low negative charge reduced protein adsorption and uptake. The in vitro uptake of macrophages and protein adsorption onto core-shell nanoparticles formed using layer-by-layer assembly has not been previously studied.

These results indicate that VEGF plays a critical role in survival and maintenance of RPE integrity. Potential undesired off-target effects should be considered with chronic use of anti-VEGF agents.

Layer-by-Layer (LbL) stepwise self-assembly of the polyelectrolytes poly(allylamine hydrochloride) and poly(styrenesulfonate) was used to create a macromolecular nanoshell around drug nanoparticles (approximately 150 nm in diameter). Dexamethasone, a steroid often used in conjugation with chemotherapy, was chosen as a model drug and was formulated into nanoparticles using a modified solvent-evaporation emulsification method. Measurement of the zeta potential (zeta-potential) after each polyelectrolyte layer was electrostatically added confirmed the successful addition of each layer. Additionally, data acquired from X-ray photon spectroscopy (XPS) indicated the presence of peaks representative of each physisorbed polyelectrolyte layer. Surface modification of the nanoshell was performed by covalently attaching poly(ethylene glycol) (PEG) with a molecular weight of 2000 to the outer surface of the nanoshell. Zeta potential measurements and XPS indicated the presence of PEG chains at the surface of the nanoshell. The polymeric nanoshell on the surface of the drug nanoparticle provides a template upon which surface modifications can be made to create a stealth or targeted drug delivery system.