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.

[Skin Leishmaniosis : Epidemiological And Clinical-Biological Study In Two Public Hospitals In Nouakchott]. / Leishmaniose Cutanee : Etude Epidemiologique Et Clinico-Biologique Dans Deux Hopitaux Publics De Nouakchott.

Many cases of cutaneous leishmaniasis are observed during hospital consultations in Nouakchott. The objective of our study is to collect all cases of cutaneous leishmaniasis in Nouakchott and to study its epidemiological and clinico-biological characteristics. METHOD: This is a prospective multicenter descriptive study conducted in two specialized hospital departments in Nouakchott from September 1st, 2016 to the end of October 2017. All patients with suspicious lesions of cutaneous leishmaniasis during this period were selected. Parasitological skin sampling, PCR and histology have been performed to patients. RESULTS: Twenty one out of 9000 patients were diagnosed during the study period, with an average age of 23 years (ranging from 3 to 70 years). A male predominance was noted with a sex ratio of 2/1. The most frequent locations are the discovered parts of the body (the 4 members). The ulcero-crusty form is encountered in 2/3 of the cases. L. major is more frequently identified (61.9%) followed by L infantum in 23.8% of cases. Meglume Antimoniate was administered intralesionally in 57.1% of patients. In Nouakchott, cutaneous leishmaniasis is not uncommon. The cases observed are related to an origin or a stay in the southern regions.

De nombreux cas de leishmaniose cutanée sont observés lors des consultations hospitalières à Nouakchott. L'objectif de notre étude est de recueillir tous les cas de leishmanioses cutanées à Nouakchott et d'en étudier les caractéristiques épidémiologiques et clinico-biologiques. MÉTHODE: Il s'agit d'une étude multicentrique descriptive prospective réalisée dans 2 services hospitaliers spécialisés de Nouakchott du 1er septembre 2016 à la fin du mois d'octobre 2017. Tous les patients présentant des lésions suspectes de leishmaniose cutanée durant cette période ont été retenus. Un prélèvement cutané à visée parasitologique, une PCR et une histologie ont été effectués aux patients. RÉSULTATS: Vingt et un patients sur 9000 consultants ont été diagnostiqués durant la période d'étude, avec un âge moyen de 23 ans (variant de 3 à 70 ans). Une prédominance masculine a été notée avec un sexe ratio de 2/1. Les localisations les plus fréquentes sont les parties découvertes du corps (les 4 membres). La forme ulcéro-crouteuse est rencontrée dans 2/3 des cas. L. major est plus fréquemment identifiée (61,9 %) suivi de L infantum dans 23,8% des cas. L'Antimoniate de Meglume a été administré par voie intralésionnelle chez 57,1% des patients. A Nouakchott, la Leishmaniose cutanée n'est pas rare. Les cas observés sont liés à une origine ou un séjour dans les régions du Sud.

Leishmaniose cutanée : étude épidémiologique et clinico-biologique dans deux hôpitaux publics de Nouakchott

De nombreux cas de leishmaniose cutanée sont observés lors des consultations hospitalières à Nouakchott. L'objectif de notre étude est de recueillir tous les cas de leishmanioses cutanées à Nouakchott et d'en étudier les caractéristiques épidémiologiques et clinico-biologiques. Méthode : Il s'agit d'une étude multicentrique descriptive prospective réalisée dans 2 services hospitaliers spécialisés de Nouakchott du 1er septembre 2016 à la fin du mois d'octobre 2017. Tous les patients présentant des lésions suspectes de leishmaniose cutanée durant cette période ont été retenus. Un prélèvement cutané à visée parasitologique, une PCR et une histologie ont été effectués aux patients. Résultats : Vingt et un patients sur 9000 consultants ont été diagnostiqués durant la période d'étude, avec un âge moyen de 23 ans (variant de 3 à 70 ans). Une prédominance masculine a été notée avec un sexe ratio de 2/1. Les localisations les plus fréquentes sont les parties découvertes du corps (les 4 membres). La forme ulcéro-crouteuse est rencontrée dans 2/3 des cas. L. major est plus fréquemment identifiée (61,9 %) suivi de L infantum dans 23,8% des cas. L'Antimoniate de Meglume a été administré par voie intralésionnelle chez 57,1% des patients. A Nouakchott, la Leishmaniose cutanée n'est pas rare. Les cas observés sont liés à une origine ou un séjour dans les régions du Sud

Flow of essential elements in subcellular fractions during oxidative stress.

Essential trace elements are commonly found in altered concentrations in the brains of patients with neurodegenerative diseases. Many studies in trace metal determination and quantification are conducted in tissue, cell culture or whole brain. In the present investigation, we determined by ICP-MS Fe, Cu, Zn, Ca, Se, Co, Cr, Mg, and Mn in organelles (mitochondria, nuclei) and whole motor neuron cell cultured in vitro. We performed experiments using two ways to access oxidative stress: cell treatments with H2O2 or Aß-42 peptide in its oligomeric form. Both treatments caused accumulation of markers of oxidative stress, such as oxidized proteins and lipids, and alteration in DNA. Regarding trace elements, cells treated with H2O2 showed higher levels of Zn and lower levels of Ca in nuclei when compared to control cells with no oxidative treatments. On the other hand, cells treated with Aß-42 peptide in its oligomeric form showed higher levels of Mg, Ca, Fe and Zn in nuclei when compared to control cells. These differences showed that metal flux in cell organelles during an intrinsic external oxidative condition (H2O2 treatment) are different from an intrinsic external neurodegenerative treatment.