During the last decades, the term “drug delivery systems” (DDSs) has almost fully replaced previously used terms, such as “dosage forms”, in an attempt to emphasize the importance of the drug carrier in ensuring the claimed safety and effectiveness of the product. However, particularly in the case of delivery devices, the term “system”, which by definition implies a profound knowledge of each single part and their interactions, is not always fully justified when using the DDS term. Within this context, dry powder inhalers (DPIs), as systems to deliver drugs via inhalation to the lungs, require a deep understanding of the complex formulation–device–patient interplay. As of now and despite the progress made in particle engineering and devices design, DPIs’ clinical performance is limited by variable patients’ breathing patterns. To circumvent this pitfall, next-generation DPIs should ideally adapt to the different respiratory capacity of individuals across age, health conditions, and other related factors. In this context, the recent wave of digitalization in the health care and industrial sectors may drive DPI technology towards addressing a personalized device–formulation–patient liaison. In this review, evolving technologies are explored and analyzed to outline the progress made as well as the gaps to fill to align novel DPIs technologies with the systems theory approach.

Mismanagement of bacterial infection therapies has undermined the reliability and efficacy of antibiotic treatments, producing a profound crisis of the antibiotic drug market. It is by now clear that tackling deadly infections demands novel strategies not only based on the mere toxicity of anti-infective compounds. Host-directed therapies have been the first example as novel treatments with alternate success. Nevertheless, recent advances in the human microbiome research have provided evidence that compounds produced by the microbial metabolism, namely postbiotics, can have significant impact on human health. Such compounds target the host-microbe-pathogen interface rescuing biotic and immune unbalances as well as inflammation, thus providing novel therapeutic opportunities. This work discusses critically, through literature review and personal contributions, these novel nonantibiotic treatment strategies for infectious disease management and resistance prevention, which could represent a paradigm change rocking the foundation of current antibiotic therapy tenets.

No abstract

In this study, an initial in vivo evaluation of a new amikacin-deoxycholate hydrophobic salt aimed at potentiating amikacin action against hard-to-treat lung infections was undertaken by quantifying, for the first time, amikacin in whole blood. Pharmacokinetic evaluation after intranasal administration in a murine model showed higher drug retention in the lungs compared to blood, with no significant differences between the salt and the free drug. Upon repeated administrations, the two treatments resulted in nonsignificant tissue damage and mild higher inflammation for the hydrophobic salt. Whole-blood analysis highlighted an unreported high partition of amikacin in blood components up to 48 h, while significant lung levels were measured up to 72 h. Such a new observation was considered responsible for the nearly overlapping pharmacokinetic profiles of the two treatments. To overcome such an issue, a dry powder in an inhalable form may be best suited. Moreover, if confirmed in humans, and considering the current once-a-day regimen for amikacin aerosols, important yet-to-be-explored clinical implications may be postulated for such amikacin persistence in the organism.

Amikacin (Amk) analysis and quantitation, for pharmacokinetics studies and other types of investigations, is conventionally performed after extraction from plasma. No report exists so far regarding drug extraction from whole blood (WB). This can represent an issue since quantification in plasma does not account for drug partitioning to the blood cell compartment, significantly underrating the drug fraction reaching the blood circulation. In the present work, the optimization of an extraction method of Amk from murine WB has been described. The extraction yield was measured by RP-HPLC-UV after derivatization with 1-fluoro-2,4-dinitrobenzene, which produced an appreciably stable derivative with a favorable UV/vis absorption. Several extraction conditions were tested: spiked Amk disulfate solution/acetonitrile/WB ratio; presence of organic acids and/or ammonium hydroxide and/or ammonium acetate in the extraction mixture; re-dissolution of the supernatant in water after a drying process under vacuum; treatment of the supernatant with a solution of inorganic salts. The use of 5% (by volume) of ammonium hydroxide in a hydro-organic solution with acetonitrile, allowed the almost quantitative (95%) extraction of the drug from WB.