Innovative Alkanediol-Based Eutectic Solvents for Extracting/Pre-Formulating Dermatologically Valuable Free Fatty Acids from Spirulina and Porphyridium Cakes.

The growing demand for phycobiliproteins from microalgae generates a significant volume of by-products, such as extraction cakes. These cakes are enriched with products of interest for the cosmetics market, namely free fatty acids, particularly polyunsaturated (PUFA). In this work, two cakes, one of spirulina and one of Porphyridium cruentum, were valorized using innovative natural hydrophobic deep eutectic solvents (NaDES) based on alkanediols. The most promising NaDES, as determined by physicochemical properties and screening, are mixtures of alkanediols and fatty acids. These include the mixtures of 1,3-propanediol and octanoic acid (1:5, mol/mol) and 1,3-propanediol and octanoic and decanoic acid (1:3:1, mol/mol). Two extractive processes were implemented: ultrasound-assisted extraction and an innovative mechanical process involving dual asymmetric centrifugation. The second process resulted in the production of extracts significantly enriched in PUFA, ranging from 65 to 220 mg/g dry matter with the two cakes. The extracts and NaDES demonstrated good safety with respect to epidermal keratinocyte viability (>80% at 200 µg/mL). The study of their impact on commensal and pathogenic cutaneous bacteria demonstrated significant effects on the viability of Staphylococcus aureus and Staphylococcus epidermidis (>50% decrease at 200 µg/mL) while preserving Corynebacterium xerosis and Cutibacterium acnes. These results highlight the potential of valorizing these co-products using alkanediol-based NaDES, in a strategy combining an active vector (NaDES) and a growth regulator extract, for the management of cutaneous dysbiosis involving staphylococci.

Synthesis, Properties, and Biodegradability of Novel Sequence-Controlled Copolyesters Composed of Glycolic Acid, Dicarboxylic Acids, and C3 or C4 Diols.

We have previously reported that sequence-controlled copolyesters such as poly((ethylene diglycolate) terephthalate) (poly(GEGT)) showed higher melting temperatures than those of the corresponding random copolymers and high biodegradability in seawater. In this study, to elucidate the effect of the diol component on their properties, a series of new sequence-controlled copolyesters composed of glycolic acid, 1,4-butanediol or 1,3-propanediol, and dicarboxylic acid units was studied. 1,4-Butylene diglycolate (GBG) and 1,3-trimethylene diglycolate (GPG) were prepared by the reactions of 1,4-dibromobutane or 1,3-dibromopropane with potassium glycolate, respectively. Polycondensation of GBG or GPG with various dicarboxylic acid chlorides produced a series of copolyesters. Terephthalic acid, 2,5-furandicarboxylic acid, and adipic acid were used as the dicarboxylic acid units. Among the copolyesters bearing terephthalate or 2,5-furandicarboxylate units, the melting temperatures (Tm) of the copolyesters containing 1,4-butanediol or 1,2-ethanediol units were substantially higher than those of the copolyester containing the 1,3-propanediol unit. Poly((1,4-butylene diglycolate) 2,5-furandicarboxylate) (poly(GBGF)) showed a Tm at 90 °C, while the corresponding random copolymer was reported to be amorphous. The glass-transition temperatures of the copolyesters decreased as the carbon number of the diol component increased. Poly(GBGF) was found to show higher biodegradability in seawater than that of poly(butylene 2,5-furandicarboxylate) (PBF). On the other hand, the hydrolysis of poly(GBGF) was suppressed in comparison with that of poly(glycolic acid). Thus, these sequence-controlled copolyesters have both improved biodegradability compared to PBF and lower hydrolyzability than PGA.

Juçara Fruit (Euterpe Edulis Martius) Valorization Combining Emergent Extraction Technologies and Aqueous Solutions of Alkanediols.

Anthocyanins from juçara fruits were extracted by pressurized liquid extraction (PLE) or ultrasound-assisted extraction (UAE), using aqueous solutions of 1,2-alkanediols and glycerol ethers as biobased solvents. The PLE (100 bar, 13 min, 1 mL/min flow rate) in the optimal extraction conditions originated 23.1 mganthocyanins·gdry biomass-1. On the other hand, the UAE was 10 min long, and the optimal conditions using 1,2-propanediol were 42.6 wt%, 160 W, and pH 7.0, leading to 50 mganthocyanins·gdry biomass-1. Extractions at the UAE optimized conditions, with aqueous solutions of five different 1,2-alkanediols and three glycerol ethers were performed, and compared to water and ethanolic extracts. The biobased solvent solutions presented anthocyanin yields up to 33% higher than water, and were shown to be as efficient as ethanol/water, but generated extracts with higher antioxidant capacity. The anthocyanin-rich extract of juçara, obtained with 1,2-propanediol, was used in the production of a natural soap and incorporated into a cream, showing that the addition of the juçara extract resulted in an antioxidant capacity in both products.

Impact of Alkanediols on Stratum Corneum Lipids and Triamcinolone Acetonide Skin Penetration.

Alkanediols are widely used as multifunctional ingredients in dermal formulations. In addition to their preservative effect, considering their possible impact on drug penetration is also essential for their use. In the present study, the influence of 2-methyl-2,4-pentanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol on the skin penetration of triamcinolone acetonide from four different semisolid formulations was investigated. Furthermore, confocal Raman spectroscopy measurements were performed to examine the influence of the alkanediols on stratum corneum lipid content and order. Alkanediols were found to increase the penetration of triamcinolone acetonide. However, the extent depends strongly on the formulation used. In certain formulations, 1,2-pentanediol showed the highest effect, while in others the penetration-enhancing effect increased with the alkyl chain length of the alkanediol used. None of the tested alkanediols extracted lipids from the stratum corneum nor reduced its thickness. Notwithstanding the above, the longer-chained alkanediols cause the lipids to be converted to a more disordered state, which favors drug penetration. This behavior could not be detected for the shorter-chained alkanediols. Therefore, their penetration-enhancing effect is supposed to be related to an interaction with the hydrophilic regions of the stratum corneum.

The effect of alkanediols on the release of triamcinolone acetonide from semisolid dosage forms.

Alkanediols are frequently used as alternative antimicrobial preservatives for dermal formulations. However, these substances can also have an influence on the biopharmaceutical properties of the applied preparations. Therefore, the influence 2-methyl-2,4-pentanediol, 1,2-pentanediol, 1,2-hexanediol and 1,2-octanediol on the release of triamcinolone acetonide (TAA) from four different commonly used semi-solid vehicles was investigated. In addition, the solubility of TAA in aqueous alkanediol solutions was evaluated. It was observed that its solubility increases as a function of chain length of the alkanediol, with exception of 1,2-octanediol. This can be related to the corresponding solubility parameters. Despite alkanediols increase the aqueous solubility of TAA, polarization microscopic images revealed that a significant amount of the drug is present in the suspended state in all formulations. Therefore, TAA release was proportional to the square root of time, indicating Higuchi kinetic. Alkanediols modify the release of TAA depending on the used base. The addition of alkanediols to the hydrogel formulation result in a slightly augmented release rate of the drug with increasing chain length of the added alkanediol. In contrast, alkanediols having longer chain lengths diminish the TAA release rate from all tested creams. Consequently, TAA release revealed to be partially inequivalent upon the addition of alkanediols.

Scilla bifolia Wax as a Source of Diverse Long-Chain Resorcinols and Alkane-1,3-diols.

GC, GC/MS and NMR analyses of Scilla bifolia washings allowed for the identification of thirty-six long-chain compounds belonging to six homologous series (five of which are from the class of resorcinols, a group of biologically important phenols): 1-alkyl-3,5-dimethoxybenzenes, 5-alkyl-3-methoxy-2-methylphenols, 3-alkyl-5-methoxyphenols, 5-alkyl-2-methylresorcinols (five compounds from each of the series); 5-alkylresorcinols (six compounds) and 1,3-alkanediols (ten compounds). Many of these compounds rarely occur in Nature. Retention indices of these compounds, as well as indices of the corresponding trimethylsilyl derivatives, were reported, some of them for the first time. The exact regiochemistry was unambiguously determined by two-dimensional NMR experiments; in some cases, the complete NMR assignment was augmented by computer spin-simulation of 1 H-NMR spectra.

Investigations on Alkanediols as Alternative Preservatives in a Nonionic Hydrophilic Cream.

Alkanediols are often used as alternative antimicrobial preservatives for dermal formulations, e.g., hydrophilic creams. These substances show an antimicrobial effect due to their amphiphilic structure. At the same time, their amphiphilic behavior enables various interactions with the cream base itself. Therefore, the effect of four different alkanediols, namely 1,2-pentanediol, 2-methyl-2,4-pentanediol (hexylene glycol), 1,2-hexanediol, and 1,2-octanediol on the physical stability of a nonionic hydrophilic cream was investigated. Further, the incorporation of the alkanediols into lamellar structures of the cream was evaluated using differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) measurements. The interaction with the mixed crystals of the cream was found to increase with raising alkyl chain length of the added alkanediol. As a result, consistency and stability of the cream are slightly impaired. A test for efficacy of antimicrobial preservation according to the European Pharmacopoeia (Ph.Eur.) revealed that the antimicrobial activity is directly linked to the length of the alkyl chain of the alkanediols. 2-Methyl-2,4-pentanediol differs from both findings. This compound has non-vicinal hydroxy groups which result in a reduced amphiphilicity compared to the others. Consequently, it has a smaller impact on the colloidal structure of the cream and shows a comparatively low antimicrobial activity.

Insights on the Extraction Performance of Alkanediols and Glycerol: Using Juglans regia L. Leaves as a Source of Bioactive Compounds.

Glycerol and alkanediols are being studied as alternative solvents to extract phytochemicals from plant material, often as hydrogen bond donors in deep eutectic solvents (DESs). Many of those alcohols are liquid at room temperature, yet studies of their use as extraction solvents are scarce. In this work, glycerol and a series of alkanediols (1,2-ethanediol, 1,2-propanediol, 1,3-propanediol, 1,3-butanediol, 1,2-pentanediol, 1,5-pentanediol, and 1,2-hexanediol) were studied for the extraction of phenolic compounds from Juglans regia L. leaves, a rich source of this class of bioactive compounds. The extraction yield was quantified, and the bioactivity of both extracts and pure solvents was evaluated by measuring the anti-inflammatory and cytotoxic activities. The solvents showing the best combined results were 1,2 and 1,3-propanediol, as their extracts presented a high amount of phenolic compounds, close to the results of ethanol, and similar cytotoxicity against cervical carcinoma cells, with no impact on non-tumor porcine liver cells in the studied concentration range. On the other hand, none of the extracts (and solvents) presented anti-inflammatory activity. Overall, the results obtained in this work contribute to the study of alternative solvents that could potentially be used also as formulation media, highlighting the importance of walnut leaves as a source of bioactive compounds.

Effect of Hydroxyl Groups on Solubilization States of Alkandiols in DTAB Micelles: Application of a Differential Conductivity Technique.

The partition coefficients, Kx, of 1,2-alkanediols and α,ω-alkanediols between dodecyltrimethylammonium bromide (DTAB) micelles and water, and the change of the degree of counterion dissociation, dα/dXam, on DTAB micelles associated with solubilization of the alkanediols are determined by a differential conductivity technique. The standard Gibbs energy change of transfer per methylene group, ΔG0(CH2), is estimated from a dependence of logarithmic value of the Kx on the carbon number of alkyl chain in the alkanediols. The dα/dXam is independent of the carbon number of alkyl chain in the alkanediols. Comparing the present results with those of DTAB/1-alkanols system, it is suggested that solubilization states of the alkanediols in DTAB micelles are as follows: 1,2-alkanediols are solubilized as its alkyl chain is oriented to micellar interior just like 1-alkanols, while α,ω-alkanediols are solubilized as its alkyl chain is partly located in micellar surface region.

Acoustic nonlinearity parameter B/A determined by means of thermodynamic method under elevated pressures for alkanediols.

The so-called Beyer nonlinearity parameter B/A is calculated for 1,2- and 1,3-propanediol, 1,2-, 1,3-, and 1,4-butanediol, as well as 2-methyl-2,4-pentanediol by means of a thermodynamic method. The calculations are made for temperatures from (293.15 to 318.15) K and pressures up to 100 MPa. The decrease in B/A values with the increasing pressure is observed. In the case of 1,3-butanediol, the results are compared with corresponding literature data. The consistency is very satisfactory. A simple relationship between the internal pressure and B/A nonlinearity parameter has also been studied.