Nanomedicines on their way through the body

(Nanowerk News) 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.
One such recently developed nanoparticle is Quaternary Ammonium Palmitoyl Glycol Chitosan (GCPQ), a chitosan-based polymeric micelle which can be used to encapsulate drugs and enhance their oral absorption and their intravenous activity by up to one order of magnitude. In spite of its great potential, the mechanisms by which GCPQ micelles – or other nanoparticle-based delivery systems – interact with organs at the cellular scale are not yet clear. However, full knowledge of these mechanisms is a prerequisite for a rational design optimizing their performance.
suggested recirculation pathway of dGCPQ particles following oral administration
(A) a schematic diagram illustrating the suggested recirculation pathway of dGCPQ particles following oral administration. The green dashed lines show the pathway of bile salts from the gall bladder into the duodenum and beyond, while the solid green lines denote the venous pathway of bile salts recruited from the gut to the liver, thence returning to the gall bladder. The yellow lines denote the passage of dGCPQ into the blood via lymphatic pathways. (B) a planar cross section through sample of mouse gall bladder harvested 120 minutes after an oral dose of dGCPQ6, a mucosal fold (MF) is marked for clarity; (C) a three-dimensional reconstruction of the same dataset, imaged over a depth of ∼50 mm in which a layer of muscle tissue (MT) is clearly visible. Contrast is derived from TPF (red) from endogenous fluorophores, SHG (blue) from collagen and epi-CARS using ωp – ωs tuned to 2100 cm-1 (green) from deuterated nanoparticles. (© Wiley)
Natalie Laura Garrett an a team of scientist from the University of Exeter and the UCL School of Pharmacy in London (UK) used multimodal nonlinear optical microscopy to investigate these mechanisms using deuterated GCPQ delivered orally to mice (see paper in Journal of Biophotonics: "Exploring uptake mechanisms of oral nanomedicines using multimodal nonlinear optical microscopy"; free access).
They combined coherent anti-Stokes Raman scattering (CARS) microscopy, second harmonic generation (SHG) and two photon fluorescence (TPF) microscopy as a multi-modal label-free method. CARS microscopy has many advantages over conventional imaging including: up to several hundred micron depth penetration into biological tissue; intrinsic optical sectioning and high spatial resolution; label-free chemically specific contrast. When combined with CARS microscopy, TPF and SHG allow detailed three-dimensional visualisation of nanoparticles pinpointed with sub-cellular precision against a complex biological background.
The multi-modal method was used to image three of the most important organs for oral drug delivery: the liver, the intestine and the gall bladder. By doing so, they demonstrated for the first time that orally administered chitosan nanoparticles follow a recirculation pathway from the gastrointestinal tract via enterocytes in the villi, pass into the blood stream and are transported to the hepatocytes and hepatocellular spaces of the liver and then to the gall bladder, before being re-released into the gut together with bile. Such recirculation may also improve drug absorption.
Source: Wiley
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