OBJECTIVE: Current preclinical therapeutic strategies involving nanomedicine require increasingly sophisticated nanosystems and the characterization of the complexity of such nanoassemblies is becoming a major issue. Accurate characterization is often the factor that can accelerate the translational approaches of nanomedicines and their pharmaceutical development to reach the clinic faster. We conducted a case study involving the adsorption of the NFL-TBS.40-63 (NFL) peptide (derived from neurofilaments) to the surface of lipid nanocapsules (LNCs) (a combined nanosystem used to target glioblastoma cells) to develop an analytical approach combining the separation and the quantification in a single step, leading to the characterization of the proportion of free peptide and thus the proportion of peptide adsorbed to the lipid nanocapsule surface.
METHODS: LNC suspensions, NFL peptide solution and LNC/NFL peptide mixtures were characterized using a Size-Exclusion Chromatography method (with a chromatographic apparatus). In addition, this method was compared to centrifugal-filtration devices, currently used in literature for this case study.
RESULTS: Combining the steps for separation and characterization in one single sequence improved the accuracy and robustness of the data and led to reproducible results. Moreover the data deviation observed for the centrifugal-filtration devices demonstrated the limits for this increasingly used characterization approach, explained by the poor separation quality and highlighting the importance for the method optimization. The high potential of the technique was shown, proving that H-bond and/or electrostatic interactions mediate adsorption of the NFL peptide to the surface of LNCs.
CONCLUSIONS: Used only as a characterization tool, the process using chromatographic apparatus is less time and solvent consuming than classical Size-Exclusion Chromatography columns only used for separation. It could be a promising tool for the scientific community for characterizing the interactions of other combinations of nanosystems and active biological agents.

This work shows the application of carbon nanocapsules as carriers for sodium ibuprofen release. Hard templating was used to prepare spherical carbon nanocapsules (mean diameter and thick shell of 690 and 70 nm, respectively), exhibiting both micro and mesoporosity. For comparison purposes, a microporous commercial activated carbon and a home-made mesoporous CMK-3 were also studied. All carbons showed similar drug uptake, although microporous commercial carbon and nanocapsules showed higher uptake at low equilibrium concentration due to higher adsorption potential in micropores. Higher and faster release of sodium ibuprofen was observed for carbon nanocapsules at pH 1.8 and 7.4 for a starting load ca. 250 mg g-1. Subsequent loading of carbon nanocapsules by successive evaporation cycles led to a remarkable load of ca. 6010 mg g-1 thanks to sodium ibuprofen filling the internal void volume. In spite of the very high load a fast release was observed at pH 7.4, reaching a release of ca. 100% of the initial sodium ibuprofen load. However, a much slower and lower release was observed at pH 1.8. Thus, the system developed has interesting features for oral drug administration thanks to low toxicity of porous carbon, low release in gastric medium and important release in intestinal medium.

Curcumin is a polyphenolic compound found in turmeric (Curcuma longa) rhizome that has potential biological benefits, including antioxidant, antimicrobial, anti-inflammatory, and anti-cancer activity. Incorporation of curcumin into functional food and beverage products, however, is challenging due to its low water-solubility, poor chemical stability, rapid metabolism, and low oral bioavailability. Researchers are, therefore developing a suite of particle-based delivery systems to maximize the potential health benefits of curcumin. Colloidal delivery systems, such as micelles, microemulsions, nanoemulsions, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, biopolymer nanoparticles, and microgels have all been developed for this purpose. The functional performance of each of these delivery systems depends on its structure and physicochemical properties, such as particle composition, particle size, morphology, physicochemical stability, optical properties, rheology, and sensory attributes. As a result, each delivery system has its advantages and disadvantages for particular applications. Consequently, a delivery system must be specifically designed for the particular bioactive agent to be encapsulated, as well as the particular food matrix it will be incorporated into. In this review, we highlight the potential of the Delivery by Design (DbD) approach for identifying and selecting the most appropriate colloidal delivery system for a particular food application, using curcumin as a model bioactive agent.

Oil-in-water (O/W) microemulsions based on Tween 80 as the emulsifier and triacetin as the dispersed oil phase were formulated to be used as delivery vehicles of Vemurafenib analog PLX4720. PLX4720 is a lipophilic antitumor drug against various cancer types correlated with the BRAFV600E mutation. The limits of the single-phase region corresponding to O/W microemulsions as described by ternary phase diagrams were examined. Droplet size measurements determined by dynamic light scattering (DLS) showed mean droplet diameters equal to 10±0.1nm both in the presence and in absence of the drug. Cryogenic-transmission electron microscopy (Cryo-TEM) images of the microemulsions showed the existence of small structures with uniform size distribution having also average diameters of approximately 10nm. Electron paramagnetic resonance (EPR) spectroscopy applying the spin probing technique confirmed PLX4720 location in the oil cores excluding its participation in the surfactants monolayer. Furthermore, cell viability assays on colon cancer cell lines Colo-205 and HT29 showed that microemulsions did not exhibit any cytotoxicity when added in ratios between 0.005% v/v and 0.2% v/v. When the cells were treated with encapsulated PLX4720 at two different concentrations (0.063 and 0.12μΜ) the same response as when dissolved in classic DMSO was observed.

An azobenzene scaffold serves as both a fluorescence quencher and nitrogen mustard deactivator in a mitochondrial targeting unit bearing theranostic drug delivery system (DDS). The DDS exhibited a tissue selectivity for tumors with aggressive phenotypes, and the efficient in vitro and in vivo azoreduction under hypoxia conditions resulted in bright fluorescence at the tumor site as well as the in situ activation of the prodrug. In vivo therapeutic experiments demonstrated a significant reduction in tumor growth versus number of controls and ex vivo tissue analysis confirmed tissue normalization with strongly reduced angiogenic markers and suppressed cell proliferation. Mechanistic insight of the DDS\'s mode of action was gained by gene and protein expression experiments, aided by a proteomic analysis, revealing the circumvention of cellular drug resistance pathways as well as the normalization of Slit-Robo signaling, and the involvement of granzyme-triggered mitochondria-mediated apoptosis. Overall, the combined high sensitivity and synthetic ease as well as excellent therapeutic response suggests a revival of the azobenzene class of hypoxia activated drugs, especially applied to theranostics, is warranted.

Implementing the solution chemistry, herein, we report the sealing of both ends of Sb2 S3 semiconductor nanotubes following the diffusion-controlled deposition of the sealing material, AgSbS2 . As a consequence, unique dumbbell-shaped hollow nanocapsules having a binary-ternary epitaxial heterojunction were formed in solution. Whereas these capsule-shaped nanostructures were obtained by the introduction of Ag(0) nanocrystals just after the formation of Sb2 S3 nanotubes, the addition of Ag(0) at the beginning of the process, prior to the formation of nanotubes, changed the growth pattern, and solid nanorods of Sb2 S3 were formed. The details of the chemistry involved in the formation of these nanostructures were investigated and are discussed herein.

In order to rationalize the nanoencapsulation process, a thermodynamic analysis allowed to predict the limit of a model drug (phenytoin, PHT) loading into poly (d, l-lactic acid) nanocarrier (PLA NC) prepared by solvent displacement method. The NC were characterized for size, morphology, thermal behavior and crystallography by dynamic light scattering, electron microscopies, differential scanning calorimetry, and powder X-ray diffraction, respectively. The drug loading, encapsulation efficiency (EE) and in vitro drug release profile were determined using high performance liquid chromatography. There was a logarithmic correlation between the partial molar free energy change based on the molecular descriptors and the drug / polymer weight (D/P) ratio predicting an equilibrium state at ratio= 0.29. This was consistent with experimental data as PHT appeared to be loaded either in crystalline or molecular/amorphous state within the PLA matrix with an average EE coefficient of 91.5%. Overall, the smallest PHT NC had a mean diameter of ≈231 nm and was produced at the limiting D/P ratio of 0.33, using PHT: 18 mg, PLA: 60 mg and surfactant: 0.3%. The drug release occurred by diffusion following Higuchi model within 24 hours. These data suggested that thermodynamic analysis allows elucidating PHT encapsulation within PLA NC and may be useful in the rationale design of other macromolecular based-nanocarriers.