Ag ⁺ is released due to a charge transfer process from the triplet state of adsorbed riboflavin to the silver nanoparticles.

The development of effective inhalable drugs remains a key challenge in the treatment of pulmonary diseases, due to the physiological barriers of the respiratory tract and the lack of predictive models that accurately reproduce the human lung environment. In this context, liposomes (LP) have emerged as promising nanocarriers for pulmonary drug delivery due to their high biocompatibility, surfactant-like composition, capacity to encapsulate both hydrophilic and lipophilic drugs, and potential to provide sustained drug release while reducing systemic toxicity. This study evaluates the influence of size and PEGylation on their physicochemical properties, cytotoxicity, interaction with the pulmonary mucus, and cellular internalisation. LP of 100 nm (LP 100), 200 nm (LP 200), and 600 nm (LP 600) were characterised physiochemically and evaluated in pulmonary cell lines (A549 and Calu-3) exposed in liquid–liquid interface (LLI) and air–liquid interface (ALI) by nebulisation. In addition, artificial pulmonary mucus (APM) was employed to analyse LP penetration through the pulmonary mucus barrier. Results indicate that LP 100 exhibits greater colloidal stability, lower cytotoxicity, and sustained migration through the APM over time with respect to larger particles. PEGylation of LP 100 (LP-PEG) further increases their stability and ability to penetrate the APM, although cellular internalisation is reduced due to the steric effect of the PEG coating. These findings highlight the importance of adjusting the size and surface modifications of LPs according to the therapeutic target of the drug, optimising their persistence on the epithelial surface or their cellular uptake.

Doxorubicin hydrochloride (DX) is a widely used chemotherapeutic agent whose severe side effects can be attenuated by suitably designing drug delivery systems. The complexation between DX and the biocompatible and biodegradable sodium alginate (ALG) results in the formation of DX@ALG nanoparticles under conditions where neither the drug nor the polymer tends to form nanoscopic structures. DX@ALG complex formation leads to the quenching of DX intrinsic fluorescence, and the drug shows chiroptical properties characteristic of supramolecular gels of DX. The association of DX and ALG into supramolecular nanoparticles takes place at low DX concentration and without salt addition. More than 99% of the moles of DX complexed with ALG form a gel-like phase, and DX@ALG nanoparticles show a high DX loading efficiency. Nanoparticle formation is revealed by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). Quantum Mechanics (QM) calculations support the formation of supramolecular DX-ALG aggregates by π–π stacking and hydrogen bonds. DX@ALG nanoparticles have been fully characterized by several spectroscopic techniques. Preliminary in vitro evaluation of DX@ALG toxicity revealed an antiproliferative activity against selected cancer cell lines.