Three novel non-nitrogenous cassane diterpenoids from Erythrophleum suaveolens (Guill. et Perr.) Brenan (Fabaceae).

During our research to contribute to the elucidation of the chemical composition of the root bark of E. suaveolens, six non-nitrogenous cassane diterpenoids (1-6) were isolated and identified. Of these secondary metabolites, three have never been previously described: Cassan-13,15-dien-3-oxo-17-oic acid (2), Cassan-15-en-[7,17]-γ-lactone (3) and 6α-hydroxy-cassamic acid (5). The other are known but, never isolated from the root barks of E. suaveolens (Fabaceae): Cassan-13,15-dien-17-oic acid (1), 6α-hydroxy-cassamic acid methyl esther (4) and cassamic acid (6). Their structures were established according to the spectroscopic data (NMR 1D and 2D, HR-ESI-MS and IR), in comparison with those of literature. The originality of this study lies in the fact that three new natural molecules were isolated and identified. In addition, all the isolated compounds (1-6) were reported for the first time from the root barks of E. suaveolens.

Development of dermopharmaceutical forms based on the fruit of Alchornea cordifolia (Euphorbiaceae) for the treatment of dermatophytes.

Our work was to develop an ointment and a lotion from the fruit juice of Alchornea cordifolia for the treatment of dermatophytes. The juice from the cold pressing of the fruit pulp of A. cordifolia was lyophilized. The ointments and lotions obtained from the lyophilizate have been evaluated in vitro on different Trichophyton species (Trichophyton rubrum, Trichophyton interdigitale, Trichophyton soudanense, and Trichophyton mentagrophytes) according to two techniques, incorporation and direct connection. In vivo tests on white mice were performed after T. mentagrophytes infestation on scarified skin parts. The reference substance was griseofulvin. The 125 mg/ml lyophilizate solution of the fruit pulp showed an activity identical to that of the 125 mg/ml solution of griseofulvin. The lotions were made with ethanol at different degrees and at concentrations of 1/50 and 1/100. Ointments at different concentrations of the lyophilizate (20%, 33%, and 50%) were made with different types of excipients. All lotions and ointments showed in vitro antifungal activity identical to that of griseofulvin up to 16 and 30 days of incubation. The ointments showed better in vivo activity compared to lotions, and the 50% vaseline-based ointment revealed an activity identical to that of griseofulvin, with a healing time of 8 days. The lyophilizate of A. cordifolia fruit juice was formulated as an ointment and lotion, maintained a good antifungal activity in vitro and in vivo on Trichophyton species, compared to griseofulvin.

Spectroscopic data of new cassane diterpenoids from the root bark of Erythrophleum suaveolens.

The data are related to the research article entitled ''New cassane diterpenoids from the root bark of Erythrophleum suaveolens'' (Jacques et al., 2019). The article provides method of purification and data to determine structure of two novel cassane diterpenoid amines: 3ß-hydroxy-3-methylbutanoyloxy-6α-hydroxy-nor-cassamine (1) and 3ß-hydroxy-3-methylbutanoyloxy-erythrosuamine (2). This data in brief provides IR, NMR and Q-TOF-MS spectra, along with fragmentation pathways that allowed to the identification of both new compounds.

Dexamethasone palmitate large porous particles: A controlled release formulation for lung delivery of corticosteroids.

We have optimized a formulation of a prodrug of dexamethasone (DXM), dexamethasone palmitate (DXP) for pulmonary delivery as a dry powder. Formulations were prepared by spray drying DXP with 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC) and Hyaluronic Acid (HA) as excipients. Large porous particles around 13 µm were produced with a tap density of 0.05g/cm3 and a Fine particle fraction around 40%. The palmitate moiety favors DXP insertion into DPPC bilayers therefore limiting its in vitro release as shown by differential scanning calorimetry. After administering DXP powder intratracheally to rats by insufflation, bronchoalveolar lavage fluid (BALF) and blood samples were collected up to 24h and DXP and DXM concentrations were determined by HPLC analysis after extraction. PK parameters were evaluated according to a non-compartmental model. We observe that DXP remains for up to 6h in the epithelial lining fluid (ELF) of the lungs at very high concentration. In addition, DXP concentration decreases according to two characteristic times. Consequently, DXM can be detected at rather important concentration in ELF up to 24h. The passage of DXP from the lungs to the bloodstream is very poor whereas DXM seems to be absorbed in the blood more easily. These results suggest that once administered DXP undergoes two different processes: hydrolysis into DXM due to the presence of esterases in the lungs and distribution in the lung tissue. This formulation appears promising to reduce systemic exposure and prolong the effect of the drug locally.

Thermosensitive and mucoadhesive pluronic-hydroxypropylmethylcellulose hydrogel containing the mini-CD4 M48U1 is a promising efficient barrier against HIV diffusion through macaque cervicovaginal mucus.

To be efficient, vaginal microbicide hydrogels should form a barrier against viral infections and prevent virus spreading through mucus. Multiple particle tracking was used to quantify the mobility of 170-nm fluorescently labeled COOH-modified polystyrene particles (COOH-PS) into thermosensitive hydrogels composed of amphiphilic triblock copolymers with block compositions EOn-POm-EOn (where EO refers to ethylene oxide and PO to propylene oxide) containing mucoadhesive hydroxypropylmethylcellulose (HPMC). COOH-PS were used to mimic the size and the surface charge of HIV-1. Analysis of COOH-PS trajectories showed that particle mobility was decreased by Pluronic hydrogels in comparison with cynomolgus macaque cervicovaginal mucus and hydroxyethylcellulose hydrogel (HEC; 1.5% by weight [wt%]) used as negative controls. Formulation of the peptide mini-CD4 M48U1 used as an anti-HIV-1 molecule into a mixture of Pluronic F127 (20 wt%) and HPMC (1 wt%) did not affect its anti-HIV-1 activity in comparison with HEC hydrogel. The 50% inhibitory concentration (IC50) was 0.53 µg/ml (0.17 µM) for M48U1-HEC and 0.58 µg/ml (0.19 µM) for M48U1-F127-HPMC. The present work suggests that hydrogels composed of F127-HPMC (20/1 wt%, respectively) can be used to create an efficient barrier against particle diffusion in comparison to conventional HEC hydrogels.

Note on the formulation of thermosensitive and mucoadhesive vaginal hydrogels containing the miniCD4 M48U1 as anti-HIV-1 microbicide.

The miniCD4 M48U1 was formulated into thermosensitive and mucoadhesive pluronic(®) hydrogels as anti-HIV-1 microbicide. The release kinetics of M48U1 from F127/HPMC (20/1 wt%) and F127/F68/HPMC (22.5/2.5/1 wt%) studied during 24h by using Franz diffusion cells showed that HEC hydrogel (1.5 wt%) used as control released 93% of the peptide, while about 25% of M48U1 remained in pluronic(®) hydrogels. The formulation of M48U1 in pluronic(®) hydrogels ensures a local delivery because no diffusion of the peptide was detected through vaginal Cynomolgus macaque mucosa using Ussing chamber. Finally, toxicological studies showed no significant difference in the HeLa cell viability of the pluronic(®) hydrogels in comparison with HEC and phosphate buffer saline.

Tracheal relaxation of five Ivorian anti-asthmatic plants: role of epithelium and K⁺ channels in the effect of the aqueous-alcoholic extract of Dichrostachys cinerea root bark.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Boerhavia diffusa (Nyctaginaceae), Baphia nitida, Cassia occidentalis, Desmodium adscendens (Fabaceae), and root bark of Dichrostachys cinerea (Fabaceae) are used in Ivory Coast for the treatment of asthma. The aim of this study was to evaluate the potential airway relaxant activity of different extracts of these plants. MATERIALS AND METHODS: Extracts of different polarities (H(2)O, EtOH/H(2)O, MeOH and CH(2)Cl(2)) were obtained from these five plants. Their ex vivo relaxant activity was tested in mice isolated trachea precontracted with carbachol (1 µM). RESULTS: Cumulative concentrations of most extracts induced moderate to strong relaxation, the methanolic extracts being the most potent and the polar extracts the most active at the concentrations used, supporting the traditional use of these five plants as anti-asthmatic remedies. We further investigated the molecular and cellular mechanisms of the mouse trachea relaxant effect of the aqueous-alcoholic extract of Dichrostachys cinerea root bark, the most potent extract. Its effect was not modified in the presence of ß-adrenoceptor antagonists (propranolol or ICI 118,551) or a PKA inhibitor (H89). By contrast, it was decreased after depolarization-induced precontraction (with 80 mM KCl), in the presence of some K(+) channels blockers [4-aminopyridine as voltage-dependent K(+) (K(v)) channel blocker and tetraethylammonium chloride as large conductance Ca(2+)-activated K(+) (BK(Ca)) channel blocker, but not with glibenclamide, an ATP-sensitive K(+) (K(ATP)) channel blocker] or after epithelium removal. CONCLUSIONS: The mouse tracheal relaxant effect of Dichrostachys cinerea EtOH/H(2)O extract was independent of ß(2)-adrenoceptors activation and cAMP/PKA pathway, but dependent on epithelium and K(+) channels, namely K(v) and BK(Ca) channels. Further investigation will be required to identify the component(s) responsible for this airways relaxant activity.

Formulation of mucoadhesive vaginal hydrogels insensitive to dilution with vaginal fluids.

The main objective of this work was to design thermosensitive and mucoadhesive vaginal hydrogels able to keep their rheological and mucoadhesive properties after dilution with vaginal fluids. Formulations were composed of pluronic F127 or a mix of two pluronics F127 and F68. Both formulations contained hydroxypropylmethyl cellulose (HPMC) as a mucoadhesive polymer. The determination of gelling temperature (T(gel)) after dilution with simulated vaginal fluid (SVF) demonstrated that hydrogels were resistant to dilution and T(gel) values were close to 30°C. Ex vivo mucoadhesion experiments conducted on porcine vaginal mucosa founded on the technique of traction of the adhesive/adherent joint allowed the characterization of mucoadhesive properties of hydrogels by measuring work of adhesion (W) and maximum force of detachment (F(max)). In the case of F127-based hydrogels, W and F(max) were lowered after dilution with SVF. However, in the case of F127/F68-based hydrogels, W, F(max) and mucoadhesion profiles were weakly affected by dilution. These differences could be attributed to the higher elasticity of F127/F68/HPMC (22.5/2.5/1% w/w) hydrogel in comparison with F127/HPMC one (20/1% w/w). Indeed, rheological analyses of the formulations showed that both elastic (G') and viscous moduli (G'') were higher for F127/F68/HPMC (22.5/2.5/1% w/w) than for F127/HPMC hydrogel (20/1% w/w). However, we demonstrated that the higher elasticity of the hydrogel was due to the higher total pluronic concentration and not due to the presence of F68 in the formulation.

What can isothermal titration microcalorimetry experiments tell us about the self-organization of surfactants into micelles?

The aim of the present review is to give a concise analysis of the thermodynamic parameters obtained from isothermal titration microcalorimetry (ITC) experiments for the characterization of the self-organization of surfactants into micelles. This review is also focused on works describing some methods allowing to overcome ITC limitation and to extract accurate thermodynamic values from ITC data.

A concise analysis of the effect of temperature and propanediol-1, 2 on Pluronic F127 micellization using isothermal titration microcalorimetry.

This article aims to explore the possibility of using isothermal titration microcalorimetry (ITC) for the investigation of F127 micellization and to study the effect of temperature and addition of propanediol-1,2 on F127 micellization behavior. From this work, ITC proved efficient to be used as a tool for the determination of the critical micellization concentration (CMC) and the enthalpy of micellization (DeltaH(mic)) of F127, from which the other thermodynamic parameters were calculated (free energy (DeltaG(mic)), entropy (DeltaS(mic)), and heat capacity of micellization (DeltaC(p,mic))). The micellization of F127 was confirmed to be a strongly endothermic process with predominance of hydrophobic interactions (TDeltaS(mic)>DeltaH(mic)) and the correlation of enthalpy and entropy of micelle formation exhibits an excellent linearity. The temperature dependence of F127 micellization was revealed by using ITC, since the CMCs values were, respectively, 0.197, 0.095, 0.085, and 0.079 mM for temperatures 28, 29, 30, and 31 degrees C. Secondly, by the addition of propanediol-1,2 to the micellization medium containing 1.187 mM of F127, the CMC was shifted to lower values (0.095, 0.081, 0.077, 0.069 and 0.066 mM, respectively, for propanediol-1,2 concentrations of 0%, 1.4%, 2.3%, 2.8%, and 3.7% w/v in the micellization medium). Finally, ITC was used as diagnostic tool with the aim of checking the reproducibility of the experiments independently on the kinetic and the dynamic aspects related to the micelle formation breakup. However, in this work we proved that the use of ITC for the determination of the CMC and thermodynamic parameters associated with F127 micellization is limited to a range of temperatures when sigmoidal curves were obtained.