Novel applications of long-established histochemical techniques to study nanoparticle-cell interactions at transmission electron microscopy

Alcian blue staining has been used to visualise nanoparticles at transmission electron microscop

Hyaluronic acid-based nanocomplexes as novel drug-nanocarriers to treat myotonic dystrophy

Hyaluronic acid-based nanocomplexes have been developpend as novel drug-nanocarriers to treat myotonic dystroph

In vitro anti-cancer activity and pharmacokinetic evaluation of curcumin-loaded lipid nanocapsules

In the present work, lipid nanocapsules (LNC) for curcumin (CCM) encapsulation have been developed and optimized. The objective was to increase drug cytotoxicity on 9L glioma cells and drug bioavailability following intravenous administration (IV). Using the phase inversion technique, we obtained 50 nm LNC loaded with CCM (4 and 6 mg/mL) and, due to the hydrophobic nature of the drug, the encapsulation efficiency was very high, being around 90%. Following 48 h of incubation with 9L cells, CCM-loaded LNC were able to reduce the viability of glioma cells resulting in significant twofold lower IC50 in comparison with the free drug solution. Moreover, CCM-loaded LNC induced both the apoptosis of 9L cells and a strong release of ATP. This suggests a cellular uptake of the LNC and an enhanced anti-proliferative effect. In order to evaluate any alteration in the pharmacokinetic behavior of the encapsulated drug, CCM-loaded LNC were injected IV into healthy rats, at a dose of 10 mg/kg. CCM pharmacokinetic studies were carried out quantifying the CCM concentration from the blood of rats, receiving either CCM-loaded LNC or free CCM solution as a control. The results demonstrated that loaded LNC exhibited a significantly higher AUC, C and t in comparison with the control, while the clearance was strongly reduced. Globally, these results encouraged the use of CCM-loaded LNC to enhance the in vivo therapeutic activity of the drug after systemic administration

Development of multifunctional lipid nanocapsules for the co-delivery of paclitaxel and CpG-ODN in the treatment of glioblastoma

In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG. This nanosystem, consisting of modified lipid nanocapsules coated with a cationic polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic drug PTX in the inner oily core, and to associate onto the surface the genetic material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with an average size of 70nm and a positive zeta potential (+25mV). They encapsulated PTX in a high amount (98%), and, due to the cationic surface charge, were able to adsorb CpG without losing stability. As a preliminary in vitro study, the apoptotic effect on GL261 glioma cells was investigated. The drug-loaded CS-LNC exhibited the ability to interact with glioma cells and induce an important apoptotic effect in comparison with blank systems. Finally, the M-LNC made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results showed that the overall survival of mice treated with the M-LNC was significantly increased in comparison with the control, Taxol(®), or the separated injection of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance imaging (MRI) which revealed the reduction of tumor growth in the animals treated with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M-LNC could potentiate both CpG immunopotency and PTX antitumor activity by enhancing its delivery into the tumor microenvironment

LES validation of lock-exchange density currents interacting with an emergent bluff obstacle

Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature B.V.We address the capability of large eddy simulation (LES) to predict the physics of density currents interacting with bluff obstacles. Most density currents of interest in engineering and geophysical applications interact with obstacles or topographic features. Validating LES solutions in these contexts is crucial to establish it as a trusted tool. We thus propose a validation effort based on simple geometries that nonetheless pose challenges common to more complex systems, including boundary layer separation and convective instabilities. We focus on lock-exchange gravity currents in the slumping phase interacting with an emergent vertical circular cylinder. Our main investment was in ensuring that the comparison of experimental data and numerical results include, at least, the velocity and the density fields , and derived quantities (e.g., second order moments). Measurements of both density and velocity fields were performed in the side and plan views for cylinder Reynolds numbers, Red, in the range 1300 to 3475. It was found that the LES accurately predicts the temporal evolution of the current front position. The computed front velocity exhibits a maximum relative error less than 8%. A good agreement between the LES and the experimental size and shape of the current head, and billows was found. The overall features upstream the cylinder, including a reflected wave, adverse pressure gradient and backflow, and downstream the cylinder, including the backflow, wake and the formation of a new head are well reproduced by LES. The agreement between the LES and the experimental time-space evolution of current spanwise- and depth-averaged density contours and the instantaneous velocity fields are not affected by Red.publishersversionpublishe