Development of a Polymeric Membrane Impregnated with Poly-Lactic Acid (PLA) Nanoparticles Loaded with Red Propolis (RP).

The main objectives of this study were to develop and characterize hydrophilic polymeric membranes impregnated with poly-lactic acid (PLA) nanoparticles (NPs) combined with red propolis (RP). Ultrasonic-assisted extraction was used to obtain 30% (w/v) red propolis hydroalcoholic extract (RPE). The NPs (75,000 g mol-1) alone and incorporated with RP (NPRP) were obtained using the solvent emulsification and diffusion technique. Biopolymeric hydrogel membranes (MNPRP) were obtained using carboxymethylcellulose (CMC) and NPRP. Their characterization was performed using thermal analysis, Fourier transform infrared (FTIR), total phenols (TPC) and flavonoids contents (TFC), and antioxidant activity through the radical scavenging assay with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and Ferric reducing antioxidant power (FRAP). The identification and quantification of significant RP markers were performed through UPLC-DAD. The NPs were evaluated for particle size, polydispersity index, and zeta potential. The TPC for RPE, NPRP, and MNPRP was 240.3 ± 3.4, 191.7 ± 0.3, and 183.4 ± 2.1 mg EGA g-1, while for TFC, the value was 37.8 ± 0.9, 35 ± 3.9, and 26.8 ± 1.9 mg EQ g-1, respectively. Relevant antioxidant activity was also observed by FRAP, with 1400.2 (RPE), 1294.2 (NPRP), and 696.2 µmol Fe2+ g-1 (MNPRP). The primary markers of RP were liquiritigenin, isoliquiritigenin, and formononetin. The particle sizes were 194.1 (NPs) and 361.2 nm (NPRP), with an encapsulation efficiency of 85.4%. Thermal analysis revealed high thermal stability for the PLA, nanoparticles, and membranes. The DSC revealed no interaction between the components. FTIR allowed for characterizing the RPE encapsulation in NPRP and CMC for the MNPRP. The membrane loaded with NPRP, fully characterized, has antioxidant capacity and may have application in the treatment of skin wounds.

Interaction between bioactive compound 11a-N-tosyl-5-deoxi-pterocarpan (LQB-223) and Calf thymus DNA: Spectroscopic approach, electrophoresis and theoretical studies.

The interaction of small molecules with DNA has been quite important, since this biomolecule is currently the major target for a wide range of drugs in clinical use or advanced clinical research phase. Thus, the present work aimed to assess the interaction process between the bioactive compound 11a-N-tosyl-5-carba-pterocarpan, (LQB-223), that presents antitumor activity, with DNA, employing spectroscopic techniques, electrophoresis, viscosity and theoretical studies. Through UV-vis and molecular fluorescence spectroscopy, it was possible to infer that the preferential quenching mechanism was static, characterized by non-fluorescent supramolecular complex formation between the LQB-223 and DNA. The binding constant was 1.94∙103Lmol-1 (30°C) and, according to the thermodynamic parameters, the main forces involved in the interaction process are hydrophobic. Potassium iodide assay, competition with ethidium bromide, fluorescence contact energy transfer and melting temperature profile of DNA were employed to evaluate the binding mode. Except for KI assay, all results obtained indicated minor groove as the preferential binding mode of LQB-223 to DNA. These observations were supported by ionic strength assay, viscosity and molecular dynamics and docking studies. Finally, electrophoresis analysis demonstrated that the interaction does not promote DNA fragmentation, but it leads to variation in the migration profile after increasing the ligand concentration.

Cardiovascular effects induced by N-(4'-dihydro)-piperoylthiomorpholine in normotensive rats.

OBJECTIVES: We have tested the cardiovascular effects of N-(4'-dihydro)-piperoylthiomorpholine (LASSBio 365) on rats using an in-vivo and in-vitro approach. METHODS: LASSBio 365 (0.025, 0.05, 0.1, 0.25, 0.5 or 1 mg/kg, randomly injected) was administered to conscious unrestrained rats and the mean arterial pressure and heart rate were measured. The effects of LASSBio 365 (3 x 10⁻6-3 x 10⁻4 m) on rat isolated aortic rings with and without endothelium were investigated. Key findings LASSBio 365 induced a dose-dependent decrease in mean arterial pressure and heart rate (ED50 = 158 ± 53 µg/kg). The effects evoked by LASSBio 365 (0.5 mg/kg) were inhibited by pretreatment with atropine. In anaesthetized rats, electrocardiogram recordings revealed second/third degree sinoatrial and atrioventricular blockade induced by the compound, which were completely inhibited after cardiac muscarinic blockade or cervical bilateral vagotomy. In rat isolated aortic rings, LASSBio 365 (3 x 10⁻6-3 x 10⁻4 m) was capable of antagonizing the contractile effects induced by phenylephrine (1 µm) or KCl (80 mm) (IC50 = 107 ± 6; 92 ± 6 µm, respectively). This effect was not inhibited after removal of the vascular endothelium (IC50 = 84 ± 4; 92 ± 10 µm, respectively). LASSBio 365 (10⁻6-10⁻4 m) antagonized CaCl2-induced contractions in a concentration-dependent manner. Furthermore, LASSBio 365 (98 µm) inhibited contractions produced by noradrenaline (1 µm), but not those induced by caffeine (20 mm). CONCLUSIONS: These results suggested that LASSBio 365 produced negative chronotropism and reduced peripheral resistance that were probably due to the stimulation of cardiac muscarinic pathways. Peripheral vasodilation was probably linked to voltage-dependent Ca²+-channel blockade and/or specific inhibition of Ca²+ release from noradrenaline-sensitive intracellular stores.

Design, synthesis and antiinflammatory activity of novel phthalimide derivatives, structurally related to thalidomide.

As part of an ongoing effort to develop new thalidomide analogues as antiinflammatory lead-candidates, this paper describes the synthesis and antiinflammatory activity of novel N-phenyl-phthalimide functionalized derivatives (4a-d, 5a,b, 6a,b). The target compounds were assayed in an acute lung inflammatory model and all compounds were able to inhibit TNF-alpha production and subsequent neutrophil recruitment in the LPS-acute lung inflammatory model.