Advanced drug delivery system utilizing a nanocarrier is the major application of nanotechnology on pharmacotherapeutics. However, despite the promising benefits and a leading trend in pharmaceutical research, nanomedicine development suffers from a poor clinical translation problem as only a handful of nanomedicine products reach the market yearly. The conventional pharmacokinetic study generally focuses only on monitoring the level of a free drug but ignores the nanocarrier's role in pharmacokinetics. One hurdle is that it is difficult to directly track intact nanocarriers in vivo to explore their pharmacokinetics. Although several imaging techniques such as radiolabeling, nuclear imaging, fluorescence imaging, etc., have been developed over the past few years, currently, one method that can successfully track the intact nanocarriers in vivo directly is by Förster resonance energy transfer (FRET). This review summarizes the application of FRET as the in vivo nanoparticle tracker for studying the in vivo pharmacokinetics of the organic nanocarriers and gives elaborative details on the techniques utilized.
25 January 2022 in Frontiers in Medical Technology
Antimicrobial peptides (AMPs) have a great potential to face the global expansion of antimicrobial resistance (AMR) associated to the development of multidrug-resistant (MDR) pathogens. AMPs are usually composed of 10–50 amino acids with a broad structural diversity and present a range of antimicrobial activities. Unfortunately, even if the oral route is the most convenient one, currently approved therapeutic AMPs are mostly administrated by the intravenous route. Thus, the development of novel drug delivery systems (DDSs) represents a promising opportunity to protect AMPs from chemical and enzymatic degradation through the gastrointestinal tract and to increase intestinal permeability leading to high bioavailability. In this review, the classification and properties as well as mechanisms of the AMPs used in infectiology are first described. Then, the different pharmaceutical forms existing in the market for oral administration are presented. Finally, the formulation technologies, including microparticle- and nanoparticle-based DDSs, used to improve the oral bioavailability of AMPs are reviewed.
Glioblastoma (GB) is the most malignant brain tumor in adults. It is characterized by angiogenesis and a high proliferative and invasive capacity. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) is of limited efficacy. Innovative anticancer drugs targeting both tumor cells and angiogenesis are urgently required, together with effective systems for their delivery to the brain. We assessed the ability of human mesenchymal stromal cells (MSCs) to uptake the multikinase inhibitor, sorafenib (SFN), and to carry this drug to a brain tumor following intranasal administration. MSCs were primed with SFN and drug content and release were quantified by analytical chemistry techniques. The ability of SFN-primed MSCs to inhibit the survival of the human U87MG GB cell line and endothelial cells was assessed in in vitro assays. These cells were then administered intranasally to nude mice bearing intracerebral U87MG xenografts. Their effect on tumor growth and angiogenesis was evaluated by magnetic resonance imaging and immunofluorescence analyses, and was compared with the intranasal administration of unprimed MSCs or SFN alone. MSCs took up about 9 pg SFN per cell, with no effect on viability, and were able to release 60% of the primed drug. The cytostatic activity of the released SFN was entirely conserved, resulting in a significant inhibition of U87MG and endothelial cell survival in vitro. Two intranasal administrations of SFN-primed MSCs in U87MG-bearing mice resulted in lower levels of tumor angiogenesis than the injection of unprimed MSCs or SFN alone, but had no effect on tumor volume. We also observed an increase in the proportion of small intratumoral vessels in animals treated with unprimed MSCs; this effect being abolished if the MSCs were primed with SFN. We show the potential of MSCs to carry SFN to brain tumors following an intranasal administration. However, the therapeutic effect is modest probably due to the pro-tumorigenic properties of MSCs, which may limit the action of the released SFN. This calls into question the suitability of MSCs for use in GB therapy and renders it necessary to find methods guaranteeing the safety of this cellular vector after drug delivery.