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

Abstract

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.

Double-headed nanosystems for oral drug delivery

“…35,36 Despite the enhanced performance of passive-nanosystems, a significant dose remained unabsorbed in the intestine, indicating potential for further improvement through active-nanosystems. 37 Recently, the focus is shifting towards exploiting intestinal receptors to improve therapeutic index of drugs encapsulated into the nanosystems. 38 The ligand-receptor stoichiometry plays an essential role in receptor mediated drug delivery.…”

Selective ultrasound contrast enhancement in the tumor by nanocapsules with perfluorooctylbromide: effect of PLGA–PEG proportion

“…AFM provided simultaneous, high-resolution imaging and mechanical property mapping of nanoparticles. 21,22 In contrast to electron microscopy, AFM does not require dry samples or use of a vacuum, but can be used directly for samples in aqueous solution, which is a great advantage. 7,22 In Fig.…”

Oral Drug Delivery Technologies—A Decade of Developments

“…It is hypothesized that, following the binding of nanoparticles to the apical membrane of M cells, internalization and shuttling to lymphocytes occur, with particle distribution being dependent on particle size and surface charge (Hussain et al, 1997;Delie, 1998). However, only a fraction of the dose is absorbed from passive nanosystems (Lamprou et al, 2013). Receptor-mediated drug delivery using functional nanosystems has been explored over the years to enhance the therapeutic index of drugs (Gref et al, 1994;Peer et al, 2007;Zhu et al, 2012;Mura et al, 2013;Cheng et al, 2015a).…”