Rúbia Darc Machado

Lafoensia pacari`s leaves have phenolic compounds which may lead to photoprotective and antioxidant properties. The aim of this study was to investigate these activities in the L. pacari phenolics-containing extract (LPE) and to obtain gel cream formulations containing LPE and that have photochemoprotective activity. Phenolic compounds and antioxidant activity were determined. Polyacrylamide & C13-14 Isoparaffin & Laureth-7 (Focus gel® 305) formulation, it added synthetic sunscreen Ethylhexyl methoxycinnamate (Eusolex 2292®) or with both Eusolex 2292® and LPE were prepared. The in vitro sun protection factor (SPF) of these formulations was determined by diffuse reflectance spectroscopy. Preliminary stability of gel creams was evaluated. Total phenols and flavonoids content were 3.31% and 0.315%, respectively. LPE showed antioxidant activity by DPPH, with an EC50 of 5.3 µg. mL-1 and by FRAP methods, in which 1g of the extract reduces 323.62 µM/L of ferrous sulfate. LPE showed an additive effect on the value of SPF when associated with Ethylhexyl methoxycinnamate, an increase of 22% in FPS of the formulation (F3). The data obtained allow us to suggest a trend towards the photoquimoprotective effect of the L. pacari phenolics-containing extract in the studied conditions.

The LQFM05 is a prototype drug designed for treatment of psychiatric disorders, such as schizophrenia, exhibiting anxiolytic- and antidepressant-like (12 or 24 µmol/kg) effects in classical behavioral tests. In order to evaluate its pharmacokinetic properties, a liquid chromatography method coupled to a quadrupole time of flight mass spectrometry system (LC-QTOF/MS) was developed and fully validated for LQFM05 analysis in rat plasma and tissue samples (brain, heart, liver, and kidneys). Liquid–liquid extraction, solid phase extraction and protein precipitation were assessed as clean-up procedures for biological samples and analyte enrichment. Plasma and tissue samples underwent protein precipitation as a preliminary step, using acetonitrile. Linearity was fully demonstrated for the dynamic range (10.0 to 900.0 ng/mL), with r² values higher than 0.99 (RSD_slope ≤ 2%, F_cal < F_tab, C_cal < C_tab). Biodistribution studies in rats revealed high brain tissue concentrations (12.4 µg/g), suggesting elevated drug affinity to the main therapeutic target tissue, showing a blood partition coefficient of 1.9. Kidneys also showed great exposure and tissue affinity, suggesting a potential extrahepatic clearance. Likewise, all examined tissues exhibited satisfactory LQFMF05 distribution. The mass fragmentation spectrum indicated the presence of its main metabolite, LQFM235, yielded by high hepatic hydroxylation route, an equally bioactive derivative. Lastly, the developed LC-QTOF/MS method was shown to be sensitive (LOQ = 10 ng/mL), precise and accurate for LQFM05 determination in tissue homogenates and plasma samples.

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-β-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-β-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (K_c < 500 M⁻¹). PSO and 5-MOP permeability rate decreased after adding HP-β-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-β-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-β-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.