Currently, problems related to antibiotic resistance are shifting the focus of pharmaceutical research towards natural molecules with antibacterial properties. Among them, flavonoids represent promising molecules with strong antibacterial features; however, they have poor biopharmaceutical properties. In this study, we developed solid lipid nanoparticles (SLNs) loaded with the flavanone naringenin (NRG) to offer an option for treating bacterial infections. NRG-SLNs systems were prepared by a solvent emulsification/diffusion and ultrasonication method, using Compritol^® 888 ATO (COM) as the lipid. The optimal formulation was obtained using a 10% (w/w) theoretical amount of NRG (NRG₁₀-SLNs), exhibiting homogeneous sizes (approximately 50 nm and 0.15 polydispersity index), negative zeta potential (−30 mV), and excellent encapsulation parameters (an encapsulation efficiency percentage of 97.9% and a drug content of 4%). NRG₁₀-SLNs presented good physical stability over 4 weeks. A cumulative drug release of 55% in 24 h and the prolonged release of the remaining amount over 10 days was observed. In addition, µ-Raman spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction measurements were carried out to characterize the drug–lipid interactions. Finally, the in vitro antibacterial and antibiofilm activities of NRG₁₀-SLNs were assayed and compared to free NRG. NRG₁₀-SLNs were bacteriostatic against Staphylococcus aureus, including the methicillin-resistant S. aureus (MRSA) and Escherichia coli strains. An improvement in the antibacterial activity of NRG-loaded SLNs compared to the free molecule was observed against S. aureus strains, probably due to the interaction of the surfactant-coated SLNs with the bacterial surface. A similar trend was observed for the biofilm inhibition.

Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers affecting the central nervous system (CNS), predominantly in adults. Despite significant advancements in this field, GB treatment still relies primarily on conventional approaches, including surgical resection, radiotherapy, and chemotherapy, which, due to its complex pathological characteristics, resistance mechanisms, and restrictive nature of the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB), remain of limited efficacy. In this context, the development of innovative therapeutic strategies able to overcome these barriers, induce cancer cell death, and improve patient prognosis is crucial. Recently, nanoparticle platforms and focused ultrasounds seem to be promising approaches for cancer treatment. Nanoparticles enable targeting and controlled release, whilst focused ultrasounds enhance tissue permeation, increasing drug accumulation in a specific organ. However, nanoparticles can suffer from synthesis complexity, long-term biocompatibility and accumulation in the body with consequent toxicity, whereas focused ultrasounds require specialized equipment and can potentially cause thermal damage, hemorrhage, or cavitation injury. Cyclodextrins (CYDs) possess good properties and represent a versatile and safer alternative able to improve drug stability, solubility, and bioavailability, and depending on the type, dose, and administration route, can reduce local and systemic toxicity. Thus, CYDs emerge as promising novel excipients in GB treatment. Despite these advantages, CYD complexes suffer from receptor specificity, reducing their potential in precision medicine. By combining CYD complexes with polymeric or lipidic platforms, the advantages of CYD safety and drug solubilization together with their specific targeting can be obtained, thus enhancing selectivity and maximizing efficacy while minimizing recurrence and systemic toxicity. This review provides a comprehensive overview of GB pathology, conventional treatments, and emerging CYD-based strategies aimed at enhancing drug delivery and therapeutic efficacy.

Rutin (RTN) is a natural flavonoid with well-documented anti-angiogenic, antioxidant, anti-inflammatory, and anti-cancer properties. However, its therapeutic potential is limited by its extremely low water solubility, which results in poor and unpredictable bioavailability. To address these limitations, we developed a new formulation that complexes RTN with a soluble polymeric β-cyclodextrin (βCPCD). βCPCD is synthesized by cross-linking polyethylene glycol (PEG) and β-cyclodextrin (βCD). The high complexing capacity of βCPCD was demonstrated by a ∼ 50-fold increase in RTN solubility and complete dissolution within 60 min. These results suggest a dual encapsulation mechanism involving (i) the inclusion of RTN within the βCD cavity and (ii) the allocation of RTN within the free volume of the three-dimensional (3D) polymeric structure. The host-guest interaction was confirmed via UV-Vis titration, NMR, µ-Raman and FTIR-ATR spectroscopy analyses. The thermal stability of the lyophilized complex was assessed by TGA, and the morphology was investigated by SEM. Preliminary docking and molecular dynamics simulations were carried out considering a local scenario consisting of a single RTN and a βCD-PEG unit. The excellent biocompatibility of βCPCD in Danio rerio zebrafish embryos (survivability > 95%) and the notable enhancement of the antiangiogenic effect of the RTN complex compared to the free drug highlight the potential of βCPCD as an effective delivery system to improve RTN performance.

In recent decades, neglected tropical diseases and poverty-related diseases have become a serious health problem worldwide. Among these pathologies, human African trypanosomiasis, and malaria present therapeutic problems due to the onset of resistance, toxicity problems and the limited spectrum of action. In this drug discovery process, rhodesain and falcipain-2, of Trypanosoma brucei rhodesiense and Plasmodium falciparum, are currently considered the most promising targets for the development of novel antitrypanosomal and antiplasmodial agents, respectively. Therefore, in our study we identified a novel lead-like compound, i.e., inhibitor 2b, which we proved to be active against both targets, with a K_i = 5.06 µM towards rhodesain and an IC₅₀ = 40.43 µM against falcipain-2.