Biljana Janković

The impact of relative humidity during electrospinning on the morphology and mechanical properties of nanofibers

Electrospinning is an efficient and flexible method for nanofiber production, but it is influenced by many systemic, process, and environmental parameters that govern the electrospun product morphology. This study systematically investigates the influence of relative humidity (RH) on the electrospinning process. The results showed that the morphology of the electrospun product (shape and diameter) can be manipulated with precise regulation of RH during electrospinning. Because the diameter of nanofibers correlates with their rigidity, it was shown that RH control can lead to manipulation of material mechanical properties. Finally, based on the solutions rheological parameter-namely, phase shift angle-we were able to predict the loss of homogenous nanofiber structure in correlation with RH conditions during electrospinning. This research addresses the mechanism of RH impact on the electrospinning process and offers the background to exploit it in order to better control nanomaterial properties and alter its applicability.

The design trend in tissue-engineering scaffolds based on nanomechanical properties of individual electrospun nanofibers

This paper especially highlights the finding that the mechanical properties of polymeric nanofibers can be tuned by changing the fiber size as well as the composition. For this purpose, the bending Youngs modulus was determined using atomic force microscope by involving single-material (polyvinyl alcohol (PVA), polyethylene oxide (PEO 400K)) and composite nanofibers (polyvinyl alcohol/hyaluronic acid (PVA/HA), polyethylene oxide/chitosan (PEO 400K/CS)). The mechanical property, namely the bending Youngs modulus, increases as the diameter of the fibers decreases from the bulk down to the nanometer regime (less than 200 nm). The ranking of increasing stiffness according to the AFM measurements of the three-point beam bending test are in agreement, and can be ranked: PEO 400K<PVA/HA≈PVA<PEO<400K/CS. According to our results, CS-based nanofibers are the stiffest (15 GPa) and the most resilient to erosion in an aqueous medium. Consequently, they possess the most appropriate attributes for bone, tendon, and cartilage tissue scaffold engineering. Nanofibers based on PVA (6 GPa) and PEO (3 GPa) are more elastic (a smaller bending Youngs modulus) and therefore are the most suitable for skin and wound tissue scaffolds.

Nanomechanical Properties of Selected Single Pharmaceutical Crystals as a Predictor of Their Bulk Behaviour

PurposeThe main goal of this research was to assess the mechanical properties of APIs’ polymorphic forms at the single-crystal level (piroxicam, famotidine, nifedipine, olanzapine) in order to predict their bulk deformational attributes, which are critical for some pharmaceutical technology processes.MethodsThe mechanical properties of oriented single crystals were determined using instrumented nanoindentation (continuous stiffness measurement). All polymorphic forms investigated were previously identified using a combination of calorimetric and spectroscopic techniques.ResultsMechanical properties such as Young’s modulus and indentation hardness were consistent with the molecular packing of the polymorphic forms investigated with respect to crystal orientation. For mechanically interlocked structures, characteristic of most polymorphic forms, response of single crystals to indentation was isotropic. The material’s bulk elastic properties can be successfully predicted by measuring Young’s modulus of single crystals because a good linear correlation with a bulk parameter such as the tablets’ elastic relaxation index was determined.ConclusionsThe results confirm the idea that the intrinsic mechanical properties of pharmaceutical crystals (Young’s modulus) largely control and anticipate their deformational behavior during tablet compression. Young’s modulus and indentation hardness represent a very valuable and effective tool in preformulation studies for describing materials’ mechanical attributes, which are important for technological processes in which materials are exposed to deformation.

Compaction properties of crystalline pharmaceutical ingredients according to the Walker model and nanomechanical attributes

This study investigates the extent to which single-crystal mechanical properties of selected active ingredients (famotidine, nifedipine, olanzapine, piroxicam) influence their bulk compressibility and compactibility. Nanomechanical attributes of oriented single crystals were determined with instrumented nanoindentation, and bulk deformational properties were assessed with the Walker and Heckel models as well as the elastic relaxation index. Good correlations were established between bulk and single-crystal plasticity parameters: the Walker coefficient and indentation hardness. The Walker model showed more practical value for evaluating bulk deformational properties of the APIs investigated because their properties differed more distinctly compared to the Heckel model. In addition, it was possible to predict the elastic properties of the materials investigated at the bulk level because a correlation between the elastic relaxation index and compliance was established. The value of using indentation hardness for crystalline APIs was also confirmed because their compactibility at the bulk level was able to be predicted. Mechanically interlocked structures were characteristic of most polymorphic forms investigated, resulting in single crystals having isotropic mechanical properties. It was revealed that in such cases good correlations between single and bulk mechanical properties can be expected. The results imply that innate crystal deformational properties define their compressibility and compactibility properties to a great extent.

Intracellular trafficking of solid lipid nanoparticles and their distribution between cells through tunneling nanotubes

The intracellular fate of nanosized drug delivery systems is still not well understood. Various internalization pathways have been discovered, but knowledge of their intracellular trafficking is still incomplete. The aim of this study was to examine the internalization, pathways, and positioning taken by solid lipid nanoparticles (SLNs) in cells. SLNs were fluorescence labeled with a newly synthesized fluorescent probe, 14-DACA. The probe was strongly incorporated into the nanoparticle core under the influence of its long lipophilic chain, enabling superior visualization of SLNs under complex and dynamic intracellular conditions. The intracellular distribution of SLNs was studied qualitatively using a co-localization technique and quantitatively using fluorescence intensity profiles. SLNs were seen inside the cells as distinct bright blue dots that underwent dynamic movement and were finally positioned in the proximity of the nucleus. A few SLNs were shown to be present in mitochondria and between actin filaments, but none in the cell nucleus or lysosomes. SLNs are here reported to be present in tunneling nanotubes (TNTs), which could be a new route of SLN transfer between cells. More TNTs were observed in cells treated with SLNs. The presence of TNTs was additionally confirmed by atomic force microscopy analysis, which indicated that treated cells were more rough than control cells. Detailed investigation of the subcellular localization of SLNs and the evidence for their transfer and distribution via TNTs to the cells, which are not in direct contact with the source of SLNs, are important for understanding the mechanism of targeted drug delivery. Understanding the possible intercellular distribution of SLNs via TNTs can significantly influence approaches to treating organelle-specific diseases.

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients.

Abstract Nanoindentation allows quantitative determination of a material’s response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision. This review highlights the application of nanoindentation for mechanical characterization of pharmaceutical materials in the preformulation phase (primary investigation of crystalline active ingredients and excipients). With nanoindentation, mechanical response can be assessed with respect to crystal structure. The technique is valuable for mechanical screening of a material at an early development phase in order to predict and better control the processes in which a material is exposed to stress such as milling and compression.

Quantification and modeling of nanomechanical properties of chlorpropamide α, β, and γ conformational polymorphs

Abstract The nanomechanical properties of the &agr;‐, &bgr;‐, and &ggr;‐ conformational polymorphs of chlorpropamide were determined by the dynamic contact module continuous stiffness measurement at nanoindenter. The mechanical anisotropy of the &agr;‐polymorph was confirmed by indenting different faces, and its deformational behavior was assigned as ductile. Based on the nanoindentation results, the &bgr; and &ggr; forms are moderately hard with plastic flow at contact points. The results revealed a correlation between Youngs modulus and inter‐planar interaction energy with regard to crystal orientation. Interpretation of the measurements was assisted by two‐ and three‐dimensional periodic density functional theory (DFT) calculations, yielding inter‐planar energies of polymorphs along the cell vectors and exhibiting a very good match with the experimental observations. The results suggest that the inter‐planar interaction energy could serve as a first‐order indicator for ranking the mechanical propensity of crystalline active ingredients. The study confirms the practical aspect of using the &agr;‐ form for preparing chlorpropamide tablets with a direct compression procedure due to its substantial level of ductility. Graphical abstract Figure. No Caption available.

Consolidation trend design based on Young's modulus of clarithromycin single crystals

The key aim of this study was to determine single mechanical properties of clarithromycin polymorphic forms in order to select some of them as more suitable for the tableting process. For this purpose, AFM single-point nanoindentation was used. The Youngs moduli of clarithromycin polymorphs were substantially different, which was consistent with the structural variations in their packing motifs. The presence of the adjacent layers, which can easily slide over each other due to the low energy barrier (the lowest Youngs modulus was 0.25 GPa) resulted in better bulk compressibility (the highest Heckel coefficient) of clarithromycin Form I. We also addressed the importance of tip geometry screening because the stress during the force mode often results in tip apex fracture. Even the initial manufacture of the diamond-coated tips can result in defects such as double-apex tips.