RESUMO
The design and development of engineered micro and nano-carriers offering superior therapeutic performance compared to traditional delivery forms, are crucial in pharmaceutical research. Aerosolization and inhalation of carriers with improved solubility/stability of insoluble drugs, has huge potential for targeted drug delivery (DD) in various pulmonary diseases. Indeed, dedicated carriers must meet specific dimensional rules for proper lung delivery. Particles between 2-10 µm in size are normally deposited in the tracheobronchial region, while particles of 0.5-2 µm may be properly deposited in the alveoli. In this work, we report the development of inhalable nanostructured carries made of a 'green' bio-inspired polymer from aqueous solutions, i.e. silk fibroin (SF), efficiently loaded with a hydrophobic drug, i.e. the thyroid hormone levothyroxine (L-T4), a drug for the treatment of idiopathic pulmonary fibrosis. The aim is to optimize a standard method for the synthesis of SF-based nanocarriers with controlled size and shape, where a fine control of their geometrical properties is aimed at efficiently controlling the pulmonary DD. L-T4 loaded SF particles were synthesized through a one-pot co-precipitation method. Optimized systems were determined by varying the chemo-physical parameters during the synthesis. Ethylenediaminetetraacetic acid (EDTA) was used to remove CaCO3 cores. The proposed synthesis routes have led to two SF structures, whose structural heterogeneity and nanostructured morphology have been demonstrated using fluorescence microscopy, DLS, SEM and EDX. Two systems with varying shape and size have been obtained: (i) a flat disk-like SF structure with an irregular surface and an in-plane length of about 1-2 µm; (ii) solid SF nanospheres, obtained using ethylene glycol as additive, showing two size populations (main diameters of 0.5 µm and 1.7 µm). Solid nanospherical systems, in particular, show a tendency to arrange into agglomerates that, when loosely bound into smaller particles, can facilitate the delivery at the alveoli. Both formulations exhibited similar drug loading efficiencies, evaluated by HPLC analysis. However, SF nanospheres showed greater in vitro drug release after 24 hours. The demonstrated control over the characteristics imparted to the proposed DD systems may be critical to select the most suitable size/shape to achieve high rates of delivery to the appropriate lung compartment.
RESUMO
As social animals, humans are strongly affected by social bonds and interpersonal interactions. Proximity and social support from significant others may buffer the negative outcomes of a painful experience. Several studies have investigated the role of romantic partners' support in pain modulation, mostly focusing on tactile support and showing its effectiveness in reducing pain perception. Nevertheless, no study so far has investigated the role of supportive speaking on pain modulation, nor has compared the effects of a tactile and vocal support within the same couples. The present study directly compared for the first time the efficacy of mere presence (Passive Support) and different forms of active (Touch, Voice, Touch + Voice) support from a romantic partner during a painful experience in a naturalistic setting. We assessed pain modulation in 37 romantic couples via both subjective (self-reported ratings) and physiological (skin conductance) measurements. We found that all three types of active support were equally more effective than passive support in reducing the painful experience at both subjective and physiological levels; interestingly, our results suggest that supportive speaking can reduce pain perception with respect to passive support to a similar extent as tactile support does. Overall, this study highlights the relevance of an active support in reducing pain perception, with active types of support being more effective than passive support, regardless of its specific modality.