Polymeric particulate technologies for oral drug delivery and targeting: A pathophysiological perspective

The oral route for delivery of pharmaceuticals is the most widely used and accepted. Nanoparticles and microparticles are increasingly being applied within this arena to optimize drug targeting and bioavailability. Frequently the carrier systems used are either constructed from or contain polymeric materials. Examples of these nanocarriers include polymeric nanoparticles, solid lipid nanocarriers, self-nanoemulsifying drug delivery systems and nanocrystals. It is the purpose of this review to describe these cutting edge technologies and specifically focus on the interaction and fate of these polymers within the gastrointestinal system

Genomic perspectives in inter-individual adverse responses following nanomedicine administration: The way forward

The underlying mechanism of intravenous infusion-related adverse reactions inherent to regulatory-approved nanomedicines still remains elusive. There are substantial inter-individual differences in observed adverse reactions, which may include cardiovascular, broncho-pulmonary, muco-cutaneous, neuro-psychosomatic and autonomic manifestations. Although nanomedicine-mediated triggering of complement activation has been suggested to be a significant contributing factor to these adverse events, complement activation may still proceed in non-responders. Whether these reactions share similar immunological mechanisms and underpinning genetic factors with drug hypersensitivity syndrome remains to be investigated. Genetic association studies could be a powerful tool to dissect causative factors and reveal the multiple molecular pathways that induce infusion related adverse reactions. It is envisaged that such research may lead to the design of reliable in vitro profiling tests for risk assessment and treatment decisions, thereby revolutionizing the practice of medicine with nanopharmaceuticals. Such procedures may further improve regulatory approval processes for nanomedicines currently in the pipeline and decrease the overall cost of health care. Here we discuss some key innate immunity genes and their polymorphisms in relation to nanomedicine infusion-mediated symptomatic responses. © 2012 Elsevier B.V

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