Neutrophils exacerbate pulmonary ischemia-reperfusion injury (IRI) resulting in poor short and long-term outcomes for lung transplant recipients. Glycolysis powers neutrophil activation, but it remains unclear if neutrophil-specific targeting of this pathway will inhibit IRI. Lipid nanoparticles containing the glycolysis flux inhibitor 2-deoxyglucose (2-DG) were conjugated to neutrophil-specific Ly6G antibodies (NP-Ly6G[2-DG]). Intravenously administered NP-Ly6G(2-DG) to mice exhibited high specificity for circulating neutrophils. NP-Ly6G(2-DG)-treated neutrophils were unable to adapt to hypoglycemic conditions of the lung airspace environment as evident by the loss of demand-induced glycolysis, reductions in glycogen and ATP content, and an increased vulnerability to apoptosis. NP-Ly6G(2-DG) treatment inhibited pulmonary IRI following hilar occlusion and orthotopic lung transplantation. IRI protection was associated with less airspace neutrophil extracellular trap generation, reduced intragraft neutrophilia, and enhanced alveolar macrophage efferocytotic clearance of neutrophils. Collectively, our data show that pharmacologically targeting glycolysis in neutrophils inhibits their activation and survival leading to reduced pulmonary IRI.

Luteolin (LUT) is a flavonoid found in several edible and medicinal plants. It is recognized for its biological activities such as antioxidant, anti-inflammatory, neuroprotective, and antitumor effects. However, the limited water solubility of LUT leads to poor absorption after oral administration. Nanoencapsulation may improve the solubility of LUT. Nanoemulsions (NE) were selected for the encapsulation of LUT due to their biodegradability, stability, and ability to control drug release. In this work, chitosan (Ch)-based NE was developed to encapsulate luteolin (NECh-LUT). A 2³ factorial design was built to obtain a formulation with optimized amounts of oil, water, and surfactants. NECh-LUT showed a mean diameter of 67.5 nm, polydispersity index 0.174, zeta potential of +12.8 mV, and encapsulation efficiency of 85.49%. Transmission electron microscopy revealed spherical shape and rheological analysis verified the Newtonian behavior of NECh-LUT. SAXS technique confirmed the bimodal characteristic of NECh-LUT, while stability analysis confirmed NECh-LUT stability when stored at room temperature for up to 30 days. Finally, in vitro release studies showed LUT controlled release up to 72 h, indicating the promising potential of NECh-LUT to be used as novel therapeutic option to treat several disorders.

Perillyl alcohol (POH), a bioactive monoterpenoid derived from limonene, shows promise as an antitumor agent for brain tumor treatment. However, its limited oral bioavailability and inadequate brain distribution hinder its efficacy. To address these challenges, this study developed nanostructured lipid carriers (NLCs) loaded with POH to improve its brain biodistribution. The NLCs prepared using hot homogenization exhibited an average diameter of 287 nm and a spherical morphology with a polydispersity index of 0.143. High encapsulation efficiency of 99.68% was achieved. X-ray diffraction analyses confirmed the semicrystalline state of POH-loaded NLCs. In vitro release studies demonstrated a biphasic release profile. Stability studies in simulated gastric and intestinal fluids confirmed their ability to withstand pH variations and digestive enzymes. In vivo pharmacokinetic studies in rats revealed significantly enhanced oral bioavailability of POH when encapsulated in the NLCs. Biodistribution studies showed increased POH concentration in brain tissue with NLCs compared with free POH, which was distributed more in non-target tissues such as the liver, lungs, kidneys, and spleen. These findings underscore the potential of NLCs as effective delivery systems for enhancing oral bioavailability and brain biodistribution of POH, providing a potential therapeutic strategy for brain tumor treatment.

Background: Croton lechleri is a native tree from Amazon Forest and its barks are used as medicine by the indigenous peoples and their descendants. This study aimed to assess the extraction sustainably of bioactive compounds from Croton lechleri barks using chemometric tools. Methods: Phenolic compounds were extracted and evaluated through 2³ factorial design and Response Surface Methodology (RSM). High performance liquid chromatography (HPLC) analysis was carried out, and its chromatographic profile was used for principal component analysis (PCA) to establish relationships between individual phenolic compound concentrations and the best extraction conditions. Global Response (GR) was performed to obtain a unique extraction condition for all dependent Croton lechleri barks’ dependent variables. Results: The total phenolic compounds (TPC) and antioxidant activity (AA) varied from 8.8 to 46.57 mg GAE/g (Gallic acid equivalent) and from 81.17 to 283 µmol Trolox/g, respectively. These parameters show coefficients determined for TPC and AA models of 99.70% and 99.80%, respectively. Gallic acid, syringic acid, epicatechin and catechin are present in the metabolism of Croton lechleri. According to HPLC analysis, the three first compounds were better extracted in lower temperatures, while catechin proved to be more stable in higher temperatures. Results showed that the best extraction conditions occurred using water as the solvent at 35 °C during 90 min of the extraction. Also, the coefficient determined for GR was 97.05%, indicating a satisfactory fit model. Conclusion: The extraction of phenolic compounds from Croton lechleri barks could be successfully performed due to the chemometric tools proposed in this research. Thus, the Croton lechleri barks bring prospects for its use as a natural antioxidant and open opportunity to explore new technological applications.