Healthcare-associated infections (HAIs) represent a global burden, leading to significant mortality and generating financial costs. One important cause of HAIs is the microbiological contamination of implantable medical devices. In this context, a novel antimicrobial drug-eluting system, based on chitosan and loaded with gentamicin, a broad-spectrum antibiotic, was developed. The effects of the addition of tannic acid and different FeSO₄ concentrations on the loaded antibiotic release were evaluated. The properties of the films were assessed in terms of thickness, swelling, mass loss and wettability. The films’ surface composition was characterized by X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy. The antibiotic release in phosphate buffer saline was quantified by high-performance liquid chromatography–mass spectrometry, and the antibacterial activity was evaluated. Hemolysis and cytotoxicity were also assessed. The results showed that the addition of tannic acid and iron decreased the swelling degree and degradation due to strong interactions between the different components, thus impacting gentamicin release for up to 35 days. In conclusion, this study presents a novel strategy to produce low-cost and biocompatible antimicrobial drug-eluting systems with sustained and prolonged antibacterial activity over more than a month.

L-asparaginase (ASNase) is an important biological drug used to treat Acute Lymphoblastic Leukemia (ALL). It catalyzes the hydrolysis of L-asparagine (Asn) in the bloodstream and, since ALL cells cannot synthesize Asn, protein synthesis is impaired leading to apoptosis. Despite its therapeutic importance, ASNase treatment is associated to side effects, mainly hypersensitivity and immunogenicity. Furthermore, degradation by plasma proteases and immunogenicity shortens the enzyme half-life. Encapsulation of ASNase in liposomes, nanostructures formed by the self-aggregation of phospholipids, is an attractive alternative to protect the enzyme from plasma proteases and enhance pharmacokinetics profile. In addition, PEGylation might prolong the in vivo circulation of liposomes owing to the spherical shielding conferred by the polyethylene (PEG) corona around the nanostructures. In this paper, ASNase was encapsulated in liposomal formulations composed by 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) containing or not different concentrations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N [methoxy (polyethylene glycol)-2000] (DSPE-PEG). Nanostructures of approximately 142–202 nm of diameter and polydispersity index (PDI) of 0.069 to 0.190 were obtained and the vesicular shape confirmed by Transmission Electron Microscopy (TEM and cryo-TEM). The encapsulation efficiency (%EE) varied from 10% to 16%. All formulations presented activity in contact with ASNase substrate, indicating the liposomes permeability to Asn and/or enzyme adsorption at the nanostructures’ surface; the highest activity was observed for DMPC/DSPE-PEG 10%. Finally, we investigated the activity against the Molt 4 leukemic cell line and found a lower IC₅₀ for the DMPC/DSPE-PEG 10% formulation in comparison to the free enzyme, indicating our system could provide in vivo activity while protecting the enzyme from immune system recognition and proteases degradation.