Deciphering the Structure and Chemical Composition of Drug Nanocarriers: From Bulk Approaches to Individual Nanoparticle Characterization

Drug nanocarriers (NCs) with sizes usually below 200 nm are gaining increasing interest in the treatment of severe diseases such as cancer and infections. Characterization methods to investigate the morphology and physicochemical properties of multifunctional NCs are key in their optimization and in the study of their in vitro and in vivo fate. Whereas a variety of methods has been developed to characterize “bulk” NCs in suspension, the scope of this review is to describe the different approaches for the NC characterization on an individual basis, for which fewer techniques are available. The accent is put on methods devoid of labelling, which could lead to artefacts. For each characterization method, the principles and approaches to analyze the data are presented in an accessible manner. Aspects related to sample preparation to avoid artefacts are indicated, and emphasis is put on examples of applications. NC characterization on an individual basis allows gaining invaluable information in terms of quality control, on: i) NC localization and fate in biological samples; ii) NC morphology and crystallinity; iii) distribution of the NC components (drugs, shells), and iv) quantification of NCs’ chemical composition. The individual characterization approaches are expected to gain increasing interest in the near future.     

Quinazoline Derivatives Designed as Efflux Pump Inhibitors: Molecular Modeling and Spectroscopic Studies

Multidrug resistance of bacteria is a worrying concern in the therapeutic field and an alternative method to combat it is designing new efflux pump inhibitors (EPIs). This article presents a molecular study of two quinazoline derivatives, labelled BG1189 and BG1190, proposed as EPIs. In silico approach investigates the pharmacodynamic and pharmacokinetic profile of BG1189 and BG1190 quinazolines. Molecular docking and predicted ADMET features suggest that BG1189 and BG1190 may represent attractive candidates as antimicrobial drugs. UV-Vis absorption spectroscopy was employed to study the time stability of quinazoline solutions in water or in dimethyl sulfoxide (DMSO), in constant environmental conditions, and to determine the influence of usual storage temperature, normal room lighting and laser radiation (photostability) on samples stability. The effects of irradiation on BG1189 and BG1190 molecules were also assessed through Fourier-transform infrared (FTIR) spectroscopy. FTIR spectra showed that laser radiation breaks some chemical bonds affecting the substituents and the quinazoline radical of the compounds.     

Poly(<Emphasis Type="Italic">β</Emphasis>-cyclodextrin)-mediated polylactide-cholesterol stereocomplex micelles for controlled drug delivery

A series of host-guest interaction-adjusted polylactide stereocomplex micelles was prepared via the self-assembly of 4-armed poly(ethylene glycol)-block-poly(L-lactide/D-lactide)-cholesterol (4-armed PEG-b-PLLA/PDLA-CHOL) and poly(β-cyclodextrin) (PCD) with the molar ratios of CHOL/β-CD at 1:0.5, 1:1, and 1:2 in an aqueous environment. The hydrodynamic diameters of the micelles ranged from 84.1 nm to 107 nm depending on the molar ratio of CHOL/β-CD. It was shown that the micelle with the largest proportion of PCD possessed excellent abilities in drug release, cell internalization as well as proliferation inhibitory effect toward human A549 lung cancer cells. The results demonstrated that the stereocomplex and host-guest interactions-mediated PLA micelles exhibited great potential in sustained drug delivery.     

Poly(β-cyclodextrin)-mediated Polylactide-cholesterol Stereocomplex Micelles for Controlled Drug Delivery

A series of host-guest interaction-adjusted polylactide stereocomplex micelles was prepared via the self-assembly of 4-armed poly(ethylene glycol)-block-poly(L-lactide/D-lactide)-cholesterol(4-armed PEG-b-PLLA/PDLA-CHOL) and poly(β-cyclodextrin)(PCD) with the molar ratios of CHOL/β-CD at 1:0.5, 1:1, and 1:2 in an aqueous environment. The hydrodynamic diameters of the micelles ranged from 84.1 nm to 107 nm depending on the molar ratio of CHOL/β-CD. It was shown that the micelle with the largest proportion of PCD possessed excellent abilities in drug release, cell internalization as well as proliferation inhibitory effect toward human A549 lung cancer cells. The results demonstrated that the stereocomplex and host-guest interactions-mediated PLA micelles exhibited great potential in sustained drug delivery.     

On the composites consisting of randomly distributed fibers

The results highlight and interpret the testing and properties of natural fibre composites including, non-destructive and high strain rate testing. The potential of this material for noise enclosures is investigated by using a coupled method cnoidal – Extended Finite Element Method (XFEM). XFEM enables the accurate approximation of solutions with jumps, discontinuities or general high gradients across interfaces. The dissipation of the sound power into a plate/cavity system shows the efficiency of this composite to achieve noise reduction better to that obtained at low and higher frequencies with traditional foams. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

On the natural Fiber (Maize) Composite material

This work is focused on the compressive behavior in the elastic region of a composite material made out of stalk-based maize fiber and unsaturated polyester resin polymer as matrix with methyl ethyl ketone peroxide as a catalyst and Cobalt Octoate as a promoter [1]. Deformation and fracture behavior are investigated by using Extended Finite Element Method (XFEM). XFEM enables the accurate approximation of solutions with jumps, discontinuities or general high gradients across interfaces between the fibers and the matrix [2], [3]. (© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Stable bundles on hypercomplex surfaces

A hypercomplex manifold is a manifold equipped with three complex structures I, J, K satisfying the quaternionic relations. Let M be a 4-dimensional compact smooth manifold equipped with a hypercomplex structure, and E be a vector bundle on M. We show that the moduli space of anti-self-dual connections on E is also hypercomplex, and admits a strong HKT metric. We also study manifolds with (4,4)-supersymmetry, that is, Riemannian manifolds equipped with a pair of strong HKT-structures that have opposite torsion. In the language of Hitchin’s and Gualtieri’s generalized complex geometry, (4,4)-manifolds are called “generalized hyperkähler manifolds”. We show that the moduli space of anti-self-dual connections on M is a (4,4)-manifold if M is equipped with a (4,4)-structure.     

Dimensionality switching through a thermally induced reversible single-crystal-to-single-crystal phase transition in a cyanide complex

The heterometallic hexanuclear cyanide-bridged complex {[Mn(bpym)(H(2)O)](2)[Fe(HB(pz)(3))(CN)(3)](4)} (1), its C(15)N and D(2)O enriched forms {[Mn(bpym)(H(2)O)](2)[Fe(HB(pz)(3))(C(15)N)(3)](4)} (2) and {[Mn(bpym)(D(2)O)](2)[Fe(HB(pz)(3))(CN)(3)](4)} (3), and the hexanuclear derivative complex {[Mn(bpym)(H(2)O)](2)[Fe(B(pz)(4))(CN)(3)](4)}·4H(2)O (4) [bpym = 2,2'-bipyrimidine, HB(pz)(3)(-) = hydrotris(1-pyrazolyl)borate, B(pz)(4)(-) = tetra(1-pyrazolyl)borate] have been synthesized. Their structures have been determined through single-crystal X-ray crystallography at different temperatures. Whereas 3 and 4 maintain a discrete hexanuclear motif during the entire temperature range investigated (down to 95 K), 1 and 2 exhibit a thermally induced reversible single-crystal to single-crystal phase transition driven by a remarkable concerted rearrangement of hydrogen and cyanide coordination bonds. While hexanuclear complexes are observed in the high temperature phases (noted 1a and 2a) above 200 K, the low temperature phases are composed of one-dimensional coordination polymers noted 1b and 2b. The magnetic properties of the four compounds have been investigated in the 2-300 K range, and they reveal the occurrence of an overall antiferromagnetic behavior. The thermal dependence of the optical reflectivity and the FT-IR absorbance have been studied for 1 in the range 10-300 K and 130-300 K, respectively. A comparative analysis of the structural and electronic properties for 1-4 clearly underlines the major role of the intermolecular interactions in the topological and dimensional rearrangement observed during the structural phase transition. This result opens new perspectives in the design of cyanide-based switchable magnetic materials using coordination bonds rearrangements.     

Using wavelets to analyze AFM images of thin films: surface micelles and supported lipid bilayers

This paper presents micro- and nanoanalysis of thin films based on images obtained by atomic force microscopy (AFM). The analysis exploits the discrete wavelet transform and the resulting wavelet spectrum to study surface features. It is demonstrated that the wavelet technique can characterize micro- and nanosurface features and distinguish between similar surface structures. The use of a feature extraction method is shown. The method involves the separation of certain frequency content from the original AFM images and analyzing the data independently to gain quantitative information about the images. By using the feature extraction method, soft surfaces in water are analyzed and nanofeatures are measured. The packing of surface micelles of sodium dodecyl sulfate on a self-assembled monolayer is analyzed. The characteristics of pore formation, due to penetration of the antibacterial peptide protegrin, into a solid-supported lipid bilayer are quantified. The sizes of the pores are obtained, and it is observed that the line tension of the pores reduces the fluctuations of the lipid bilayer.