Degradation of Drug Delivery Nanocarriers and Payload Release: A Review of Physical Methods for Tracing Nanocarrier Biological Fate

Abstract

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.

Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability

“…On the other hand, formulated therapeutics should finally be susceptible to metabolic transformation and excreted from the body. This dilemma is in the focus of attention in [27], with the methods for monitoring the biological fate of drugs and nanocarriers emphasized. Noteworthy, immune system and related cells play significant roles in the degradation pathway.…”

Cellular uptake and retention studies of silica nanoparticles utilizing senescent fibroblasts

“…NPs used as drug carriers are constructed from a variety of substances, including lipids, metals, and natural or synthetic polymers 1 . The size, concentration, shape, material, and surface charge of NPs are augmentable parameters for enhancing their biofunctionality and tune their interaction and cellular uptake 2 – 5 . Improved therapeutic profiles, higher bioavailability, and lower off target toxicity of the carried therapeutic are some of the desired outcomes for NP-delivery platforms.…”

Shining Light on Polymeric Drug Nanocarriers with Fluorescence Correlation Spectroscopy

“…It is clear that a combination of complementary experimental methods has to be used in order to obtain a comprehensive understanding on the fate of the NCs during the whole delivery process. While a broad range of such methods for NCs characterization have been discussed in recent reviews, [9,10] in this M. Barz Leiden Academic Centre for Drug Research (LACDR) Leiden University Einsteinweg 55, Leiden 2333 CC, The Netherlands Figure 1. Schematic representation of a typical confocal FCS setup and its principle of operation.…”

“…It is clear that a combination of complementary experimental methods has to be used in order to obtain a comprehensive understanding on the fate of the NCs during the whole delivery process. While a broad range of such methods for NCs characterization have been discussed in recent reviews, [ 9,10 ] in this review we focus on the fluorescence correlation spectroscopy technique, which can assist to provide a deeper insight, especially in a complex biological environment. We show that due to its single molecule sensitivity, selectivity, and very small (<1 µm 3 ) probing volume, FCS can serve as a powerful and versatile tool for the characterization of fluorescently labeled polymeric NCs at all stages of the delivery process and provide information on size, surface functionalization, drug loading efficiency, interactions with plasma proteins or other species as well as on triggered or premature decomposition and/or cargo release.…”