Exploring uptake mechanisms of oral nanomedicines using multimodal nonlinear optical microscopy.

TitleExploring uptake mechanisms of oral nanomedicines using multimodal nonlinear optical microscopy.
Publication TypeJournal Article
Year of Publication2012
AuthorsGarrett NLaura, Lalatsa A, Uchegbu I, Schätzlein A, Moger J
JournalJ Biophotonics
Date Published2012 May
KeywordsAdministration, Oral, Animals, Biological Transport, Male, Mice, Mice, Inbred BALB C, Microscopy, Fluorescence, Multiphoton, Nanomedicine, Nanoparticles, Optical Processes, Organ Specificity, Polymers, Spectrum Analysis, Raman

Advances in pharmaceutical nanotechnology have yielded ever increasingly sophisticated nanoparticles for medicine delivery. When administered via oral, intravenous, ocular and transcutaneous delivery routes, these nanoparticles can elicit enhanced drug performance. In spite of this, little is known about the mechanistic processes underlying interactions between nanoparticles and tissues, or how these correlate with improved pharmaceutical effects. These mechanisms must be fully understood before nanomedicines can be rationally engineered to optimise their performance. Methods to directly visualise these particulates within tissue samples have traditionally involved imaging modalities requiring covalent labelling of fluorescent or radioisotope contrast agents. We present CARS, second harmonic generation and two photon fluorescence microscopy combined as a multi-modal label-free method for pinpointing polymeric nanoparticles within the stomach, intestine, gall bladder and liver. We demonstrate for the first time that orally administered chitosan nanoparticles follow a recirculation pathway from the GI tract via enterocytes, to the liver hepatocytes and intercellular spaces and then to the gall bladder, before being re-released into the gut together with bile.

Alternate JournalJ Biophotonics
PubMed ID22389316