Exploring uptake mechanisms of oral nanomedicines using multimodal nonlinear optical microscopy

Natalie Laura Garrett, Aikaterini Lalatsa, Ijeoma Uchegbu, Andreas Schatzlein, Julian Moger

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)458-468
Number of pages11
JournalJournal of Biophotonics
Volume5
Issue number5-6
Early online date5 Mar 2012
DOIs
Publication statusPublished - May 2012

Keywords

  • Administration, Oral
  • Animals
  • Biological Transport
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Fluorescence, Multiphoton
  • Nanomedicine
  • Nanoparticles
  • Optical Processes
  • Organ Specificity
  • Polymers
  • Spectrum Analysis, Raman

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