Penetration enhancing effects of selected natural oils utilized in topical dosage forms

Abstract

Context: Various natural products, including oils, have been utilized as penetration enhancers due to their “safety profiles”. These oils contain fatty acids promoting skin permeability through lipid fluidization within the stratum corneum; and might therefore be able to effectively enhance transdermal drug delivery.

Objective: We investigated possible penetration enhancing properties of selected oils, utilizing flurbiprofen as marker compound in emulgel formulations. The formulations were compared to a liquid paraffin emulgel and a hydrogel to establish any significant penetration enhancing effects.

Methods: Gas chromatographic analysis of the natural oils was performed at ambient temperature to determine the fatty acid composition in each selected natural oils. Franz cell diffusion studies and tape stripping methods were employed to study delivery of the marker into, and through the skin.

Results: The following rank order for the emulgel flux-values was obtained: Hydrogel >>>> olive oil >> liquid paraffin >> coconut oil > grape seed oil >> Avocado oil ≥ Crocodile oil >> Emu oil.

Discussion: Results suggested that oils containing predominantly mono-unsaturated oleic acid, on average increased the flux of the marker to a larger extent than oils containing an almost even mixture of both mono- and poly-unsaturated fatty acids. Oils comprising saturated fatty acids (SFAs) with alkyl chains between C₁₂ and C₁₄, increased the marker flux to a higher extent than oils containing C₁₆–C₁₈ SFAs. Effects observed for branched fatty acids, however, did not vary significantly from effects for unbranched fatty acids with the same carbon chain length.

Conclusion: Natural oils possess penetration enhancing effects.     

Transitioning to sustainable urban water management systems: how to define expected service functions?

Sustainable water management is a worldwide challenge for the twenty-first century. It involves replacing traditional management approaches with a new concept, often referred to as sustainable urban water management (SUWM). This paradigm shift means that SUWM systems must include new services, some of which have already emerged. However, no publications have presented the expected SUWM system in terms of the full range of services it would need to include, and no publications have proposed a method for identifying the services the system must provide. This paper proposes a method for identifying these services and presents a generic petal diagram to represent the service functions of the SUWM system. Moreover, this paper presents a new method for defining these services in a specific territory. This method is based on the confrontation between a general representation and the objectives of the stakeholders in a given system in a given territory. The method is illustrated with a full-scale case study on the Doua eco-campus (Lyon University). This method is intended to aid practitioners to manage its system and to transition to SUWM. It is designed to improve the transparency of decision formulation and to involve stakeholders in the process.     

Phenolic composition in different genotypes of Guabiju fruits (Myrcianthes pungens) and their potential as antioxidant and antichemotactic agents

Fruits of Myrcianthes pungens Berg. Legr. (Myrtaceae), known as guabiju, are widely consumed fresh as well as dried, processed into jam, marmalade, and juices. In this study, chemical composition and antichemotactic and antioxidant activities of fruits from a wild type (GB) and 2 genotypes, PL2 and PL1, of guabiju were investigated. Total anthocyanins for the genotypes ranged from 334 to 531 mg/100 g dry weight (dwt). Total flavonoids and polyphenols ranged from 79.8 to 154 mg/100 g and 2438 to 4613 mg/100 g (dwt), respectively. A reversed phase liquid chromatography method with photodiode array detection was used to determine chemical profiles of the main anthocyanins found in the extracts. An HPLC method for the quantification of flavonoids is proposed, providing a simple procedure with rapid sample preparation. All samples contained 5 identical anthocyanidins, distributed differently, with cyanidin as the main compound. Identified flavonoids were quercitrin, hyperoside, and isoquercitrin; their relative amounts varied among the extracts. The antioxidant activity of guabiju methanolic extract was comparable to that of Trolox, and at a test concentration of 0.25 mg/mL, GB and PL2 activities were higher than those exhibited by Trolox. Total dry extracts of guabiju exhibited greater inhibition of chemotaxis at a concentration of 4 μg/mL, except for GBH (wild-type hydrolyzed extract) which already presented high values at a concentration of 2 μg/mL. These results suggest that the consumption of this fruit, rich in polyphenols, may be beneficial to human health. Practical Application: The paper is the first attempt on the improvement of this native fruit, since it is widely consumed regularly as part of the South American diet. The content of phenolic compounds demonstrates that consumption of guabiju would be beneficial to human health. Differences among samples, originating from open pollination of plants growing on the same site, lead to the conclusion that improvements can be made in the chemical composition and beneficial activity of guabiju fruits by simply selecting genotypes for these characteristics among open-pollinated seedlings.     

Hydrothermal treatment of strand particles of pine for the improvement of OSB panels

The aim of this study was to evaluate the effect of hydrothermal treatment in strand particles of pine used for oriented strand boards (OSB) production. Strand particles of pine were hydrothermally treated at 130, 150 and 170 °C for 7 and 21 min, for the determination of chemical composition, pH, equilibrium moisture content, particles mass loss, and contact angle of these particles with phenol–formaldehyde resin. Afterwards, OSB panels were produced using 8% phenol–formaldehyde resin, with a nominal density of 0.7 g/cm³, and pressing cycle at 170 °C and 3.14 MPa for 8 min. Then, the panels were kept in climate chamber until mass stabilization for the determination of their physical and mechanical properties, and for comparison with the European standards. The hydrothermal treatment in the particles decreased carbohydrate, especially mannan, xylan and arabinans, resulting in reduced equilibrium moisture content, pH, and contact angle, and increasing buffer capacity and mass loss. In OSB panels, treated particles caused the drop in the equilibrium moisture content and reduction of the thickness swelling of the panel, without reducing the mechanical strength, making the hydrothermal treatment very attractive. The hydrothermal treatment at 170 °C for 7 min allowed the resulting OSB panel being classified into the categories 1 and 2 of the European standard, expanding its range of use.     

Protein Ligation-Assisted Reconstitution of Split HRP Fragments for Facile Production of HRP Fusion Proteins in E. coli

Horseradish peroxidase (HRP) is a pivotal biocatalyst for biosensor development and fine chemical synthesis. HRP proteins are mostly extracted and purified from the roots of horseradish because the solubility and productivity of recombinant HRP in bacteria are significantly low. In this study, we investigate the reconstitution system of split HRP fragments to improve its soluble expression levels in E. coli allowing the cost-effective production of bioactive HRPs. To promote the effective association between two HRP fragments (HRPn and HRPc), we exploit SpyTag-SpyCatcher chemistry, a versatile protein coupling method with high affinity and selectivity. Each HRP fragment was genetically fused with SpyTag and SpyCatcher, respectively, exhibiting soluble expression in the E. coli cytoplasm. The engineered split HRPs were effectively and irreversibly reconstituted into a biologically active and stable assembly that can catalyze intrinsic enzymatic reactions. Compared to the chaperone co-expression system, our approach shows that the production yield of soluble HRP is comparable, but the purity of the final product is relatively high. Therefore, our results can be applied to the high-yield production of recombinant HRP variants and other difficult-to-express proteins in bacteria without complex downstream processes.     

Spin-Crossover Grafted Monolayer of a Co(II) Terpyridine Derivative Functionalized with Carboxylic Acid Groups

The synthesis and characterization of a new Co(II) spin-crossover (SCO) complex based on 4′-(4-carboxyphenyl)−2,2′:6′,2″-terpyridine ligand are reported. This complex can be successfully grafted on silver surface maintaining the SCO behavior. Thus, atomic force microscopy (AFM), matrix assisted laser desorption ionization – time-of-flight mass spectrometry (MALDI-TOF MS), Raman spectroscopy, and XPS measurements, upon surface deposition, evidence the formation of a monolayer of intact molecules grafted through carboxylate groups to the Ag surface. Three different techniques: Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and X-ray absorption spectroscopy (XAS), supported by first-principles calculations, confirm that the deposited molecules undergo a gradual spin transition with temperature. This phenomenon is unprecedented for a monolayer of molecules directly grafted onto a metallic surface from solution.     

Synthesis and SAR Studies of Isoquinoline and Tetrahydroisoquinoline Derivatives as Melatonin Receptor Ligands

In our constant search for new successors of agomelatine, we report herein a new series of compounds resulting from bioisosteric modulation of the naphthalene ring. The isoquinoline and tetrahydroisoquinoline derivatives were synthesized and pharmacologically evaluated. This isosteric replacement of the naphthalene group of agomelatine has led to potent agonist and partial agonist compounds with nanomolar melatonergic binding affinities. Overall, the presence of a nitrogen atom was accompanied with a decrease in the binding affinity toward both MT₁ and MT₂ and the loss of 5HT_2C response, especially for tetrahydroisoquinoline in comparison with the parent compound. Interestingly, due to the presence of this nitrogen atom, a notable improvement in the pharmacokinetic properties was observed for all compounds.