Characterization techniques for studying the properties of nanocarriers for systemic delivery

Nanocarriers have attracted a huge interest in the last decade as efficient drug delivery systems and diagnostic tools. They enable effective, targeted, controlled delivery of therapeutic molecules while lowering the side effects caused during the treatment. The physicochemical properties of nanoparticles determine their in vivo pharmacokinetics, biodistribution and tolerability. The most analyzed among these physicochemical properties are shape, size, surface charge and porosity and several techniques have been used to characterize these specific properties. These different techniques assess the particles under varying conditions, such as physical state, solvents etc. and as such probe, in addition to the particles themselves, artifacts due to sample preparation or environment during measurement. Here, we discuss the different methods to precisely evaluate these properties, including their advantages or disadvantages. In several cases, there are physical properties that can be evaluated by more than one technique. Different strengths and limitations of each technique complicate the choice of the most suitable method, while often a combinatorial characterization approach is needed

Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Intravenously injected nanopharmaceuticals induce adverse cardiopulmonary reactions in sensitive human subjects and these reactions are reproducible in pigs. The underlying mechanisms are poorly understood, but a role for both the complement system and reactive macrophages has been implicated. Here we show the dominance and importance of early pulmonary intravascular macrophage clearance kinetics in adverse particle-mediated cardiopulmonary distress in pigs and irrespective of complement activation. Delaying particle recognition by macrophages within the first few minutes of injection overcome adverse reactions in pigs. This was achieved by two independent approaches: (i) changing particle geometry from a spherical shape (which trigger cardiopulmonary distress) to either rod- or disk-shape morphology and (ii) by physically adhering spheres to the surface of erythrocytes. These approaches bypasses particle surface engineering approaches to prevent robust macrophage recognition as well as the use of immunological or pharmacological modulators to reduce/overcome nanomedicine related adverse cardiopulmonary distress