Versatile Palladium-catalyzed intramolecular cyclization to access new luminescent azaphosphaphenalene motifs.

Using a straightforward sequence of diphosphonylation and a Pd-catalysed concerted-metalation-deprotonation (CMD), a synthetic strategy towards polyaromatic phosphorus containing heterocycles was developed. Herein, we report the synthesis and characterization of new azaphosphaphenalenes, using easily accessible palladium catalysts and starting materials. The key tetrahydroquinoline intermediates of the reaction were synthesised via a fast and effective procedure and could be isolated as such, or further reacted towards the target polyaromatic structures. The obtained products showed interesting luminescent properties and their emission, excitation and quantum yields were evaluated.

Monoketonic Curcuminoid-Lidocaine Co-Deliver Using Thermosensitive Organogels: From Drug Synthesis to Epidermis Structural Studies.

Organogels (ORGs) are remarkable matrices due to their versatile chemical composition and straightforward preparation. This study proposes the development of ORGs as dual drug-carrier systems, considering the application of synthetic monoketonic curcuminoid (m-CUR) and lidocaine (LDC) to treat topical inflammatory lesions. The monoketone curcuminoid (m-CUR) was synthesized by using an innovative method via a NbCl5-acid catalysis. ORGs were prepared by associating an aqueous phase composed of Pluronic F127 and LDC hydrochloride with an organic phase comprising isopropyl myristate (IPM), soy lecithin (LEC), and the synthesized m-CUR. Physicochemical characterization was performed to evaluate the influence of the organic phase on the ORGs supramolecular organization, permeation profiles, cytotoxicity, and epidermis structural characteristics. The physico-chemical properties of the ORGs were shown to be strongly dependent on the oil phase constitution. Results revealed that the incorporation of LEC and m-CUR shifted the sol-gel transition temperature, and that the addition of LDC enhanced the rheological G'/G″ ratio to higher values compared to original ORGs. Consequently, highly structured gels lead to gradual and controlled LDC permeation profiles from the ORG formulations. Porcine ear skin epidermis was treated with ORGs and evaluated by infrared spectroscopy (FTIR), where the stratum corneum lipids were shown to transition from a hexagonal to a liquid crystal phase. Quantitative optical coherence tomography (OCT) analysis revealed that LEC and m-CUR additives modify skin structuring. Data from this study pointed ORGs as promising formulations for skin-delivery.

Physicochemical data of oleic acid-poloxamer organogel for intravaginal voriconazole delivery.

Functional polymeric nanoparticles have attracted attention for different biomedical applications, including drug delivery. Poloxamers (PL), a synthetic copolymers of poly(ethyleneoxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), that exhibit thermoreversible behavior in aqueous solutions. Physicochemical properties of Oleic Acid-Poloxamer (OA-PL) organogel for intravaginal controlled Voriconazole (VRC) delivery were assessed using three different oils (isopropyl myristate - IPM, isopropyl palmitate - IPP, and oleic acid - OA, in order to select the most suitable oil phase for increasing the solubility of the drug and its dispersion in the final aqueous phase. Organogel structural organization was assessed by VRC partition coefficient, differential scanning calorimetry (DSC), rheological analysis, and drug release assay. These data are complementary to the research article entitled "Sodium alginate in oil-poloxamer organogels for intravaginal drug delivery: influence on structural parameters, drug release mechanisms, cytotoxicity and in vitro antifungal activity" - Materials Science and Engineering: C, 2019. 99: p. 1350-1361.

Sodium alginate in oil-poloxamer organogels for intravaginal drug delivery: Influence on structural parameters, drug release mechanisms, cytotoxicity and in vitro antifungal activity.

Local administration of antimicrobial agents is the first therapeutic approach for the treatment of Candida albicans infections. The duration of contact of formulations with the vaginal mucosa is critical for therapeutic efficacy. This study describes the development of organogels employing an oil phase composed of oleic acid (OA) and an aqueous phase consisting of the poloxamer PL407, alone or in association with PL188, together with 0.25-1% sodium alginate (SA), in order to obtain an intravaginal drug delivery system capable of modulating the release of voriconazole (VRC). VRC was solubilized in oleic acid homogenized with the PL-SA aqueous phase, at a final concentration of 5 mg/mL. Physicochemical characterization was performed for evaluation of the influence of SA on organogel structural organization, biopharmaceutical properties, pharmacological efficacy, and cytotoxicity, envisaging use of the formulation for the treatment of vaginal candidiasis. The enthalpy variation values showed greater changes in the presence of PL188 and after the incorporation of SA or VRC in the organogels. Rheological analysis showed Tsol-gel values in the ranges 11-39 °C and 27-30 °C for the OA-PL407 and OA-PL407-188 formulations, respectively. Oscillatory analysis of OA-PL407-188 showed that G' was ~20-fold higher than G″, even after submitting the formulation to temperature variation. VRC-OA-PL407 showed fast drug release from 0.5 to 4 h, maintaining total release (~100%) up to 24 h. The incorporation of SA in the organogels enabled modulation of VRC release, with different release percentages for 0.25% SA (~75%), 0.5% SA (~55%), and 1% SA (~35%). The formulation was non-cytotoxic towards HeLa and Vero cell lines. In diffusion tests, it was able to prevent the growth of Candida albicans and Candida krusei. In conclusion, the results suggested that OA-PL407-188-SA organogels could be possible new systems for VRC delivery, with potential for use in future vaginal applications.