Atomic Force Microscopy Images Label-Free, Drug Encapsulated Nanoparticles In Vivo and Detects Difference in Tissue Mechanical Properties of Treated and Untreated: A Tip for Nanotoxicology

Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ~280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics

Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic ß-cells for effective management of type 1 diabetes mellitus

Background and Purpose: Approaches to prevent selective and progressive loss of insulin-producing ß-cells in Type 1 diabetes mellitus (T1DM) will help conquer this prevalent and devastating disease. Curcumin (CUR), a natural anti-inflammatory, suppresses diabetes associated inflammation and cell death. However, very high doses have been tested owing to poor oral bioavailability, making it difficult to translate to the clinic. Experimental approach: We recently prepared biodegradable nanosystems encapsulating curcumin (nCUR), resulting in at least 9-fold improvement in oral bioavailability. In the current study, we tested nCUR's ability to prevent streptozotocin (STZ)-induced inflammation and apoptosis in pancreatic islet/ß-cells. Key Results: Nonfasted rats pretreated with 10 or 50 mg/kg nCUR 6 hours prior to STZ challenge had up to 37% reduction in the glucose levels, while plain CUR (50 mg/kg) results in 12% reduction. This is owing to nCUR's ability to prevent islet/β-cell death evident from TUNEL assay, and H&E staining. Both CUR and nCUR significantly decreased levels of inflammatory cytokines in pancreatic tissue homogenates that correlated well with minimal histiocytic infiltration. The nCUR, rather than CUR pre-treatment prevented 8-oxo-2'-deoxyguanosine (8-oxo-dG), a sensitive biomarker of reactive oxygen species (ROS)-induced DNA damage in pancreas. Our data in normal rodents indicates that 28 days daily dosing with nCUR (25 to 100 mg/kg) did not cause any deleterious health issues by the carrier. Conclusions & Implications: Together, these data indicate a potentially translatable dose of nCUR that is safe and efficacious in improving the ß-cell function, possibly preventing T1DM