The active targeting to alveolar macrophages (AM) is an attractive strategy to improve the therapeutic efficacy of ‘old’ drugs currently used in clinical practice for the treatment of pulmonary tuberculosis. Previous studies highlighted the ability of respirable solid lipid nanoparticle assemblies (SLNas), loaded with rifampicin (RIF) and functionalized with a novel synthesized mannose-based surfactant (MS), both alone and in a blend with sodium taurocholate, to efficiently target the AM via mannose receptor-mediated mechanism. Here, we present the in vivo biodistribution of these mannosylated SLNas, in comparison with the behavior of both non-functionalized SLNas and bare RIF. SLNas biodistribution was assessed, after intratracheal instillation in mice, by whole-body real-time fluorescence imaging in living animals and RIF quantification in excised organs and plasma. Additionally, SLNas cell uptake was determined by using fluorescence microscopy on AM from bronchoalveolar lavage fluid and alveolar epithelium from lung dissections. Finally, histopathological evaluation was performed on lungs 24 h after administration. SLNas functionalized with MS alone generated the highest retention in lungs associated with a poor spreading in extra-pulmonary regions. This effect could be probably due to a greater AM phagocytosis with respect to SLNas devoid of mannose on their surface. The results obtained pointed out the unique ability of the nanoparticle surface decoration to provide a potential more efficient treatment restricted to the lungs where the primary tuberculosis infection is located.

The main focus of the current research was the characterization of the by-products from the steam distillation of Lavandula angustifolia Mill. (LA) and Lavandula x intermedia Emeric ex Loisel (LI) aerial parts, as they are important sources of bioactive compounds suitable for several applications in the food, cosmetic, and pharmaceutical industries. The oil-exhausted biomasses were extracted and the total polyphenol and flavonoid contents were, respectively, 19.22 ± 4.16 and 1.56 ± 0.21 mg/g for LA extract and 17.06 ± 3.31 and 1.41 ± 0.10 mg/g for LI extract. The qualitative analysis by liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS) revealed that both the extracts were rich in phenolic acids and glycosylated flavonoids. The extracts exhibited radical scavenging, chelating, reducing activities, and inhibitory capacities on acetylcholinesterase and tyrosinase. The IC50 values against acetylcholinesterase and tyrosinase were, respectively, 5.35 ± 0.47 and 5.26 ± 0.02 mg/mL for LA, and 6.67 ± 0.12 and 6.56 ± 0.16 mg/mL for LI extracts. In conclusion, the oil-exhausted biomasses demonstrated to represent important sources of bioactive compounds, suitable for several applications in the food, cosmetic, and pharmaceutical industries.

In the present work, the applicability of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, coupled with chemometric tools in recognizing essential oils (EOs) for routine control, was evaluated. EOs belonging to Mentha, Cymbopogon, and Lavandula families and to S. rosmarinus and T. vulgaris species were analyzed, and the performance of several untargeted approaches, based on the synergistic combination of ATR-FTIR and Partial Least Squares Discriminant Analysis (PLS-DA), was tested to classify the species and chemotypes. Different spectra pre-processing methods were employed, and the robustness of the built models was tested by means of a Receiver Operating Characteristic (ROC) curve and random permutations test. The application of these approaches revealed fruitful results in terms of sensitivity and specificity, highlighting the potentiality of ATR-FTIR and chemometrics techniques to be used as a sensitive, cost-effective, and rapid tool to differentiate EO samples according to their species and chemotype.

The mimicking of physiological conditions is crucial for the success of accurate in vitro studies. For inhaled nanoparticles, which are designed for being deposited on alveolar epithelium and taken up by macrophages, it is relevant to investigate the interactions with pulmonary surfactant lining alveoli. As a matter of fact, the formation of a lipid corona layer around the nanoparticles could modulate the cell internalization and the fate of the transported drugs. Based on this concept, the present research focused on the interactions between pulmonary surfactant and Solid Lipid Nanoparticle assemblies (SLNas), loaded with rifampicin, an anti-tuberculosis drug. SLNas were functionalized with a synthesized mannosylated surfactant, both alone and in a blend with sodium taurocholate, to achieve an active targeting to mannose receptors present on alveolar macrophages (AM). Physico-chemical properties of the mannosylated SLNas satisfied the requirements relative to suitable respirability, drug payload, and AM active targeting. Our studies have shown that a lipid corona is formed around SLNas in the presence of Curosurf, a commercial substitute of the natural pulmonary surfactant. The lipid corona promoted an additional resistance to the drug diffusion for SLNas functionalized with the mannosylated surfactant and this improved drug retention within SLNas before AM phagocytosis takes place. Moreover, lipid corona formation did not modify the role of nanoparticle mannosylation towards the specific receptors on MH-S cell membrane.