Niosomes for Topical Application of Antioxidant Molecules: Design and In Vitro Behavior

In the present study, gels based on xanthan gum and poloxamer 407 have been developed and characterized in order to convey natural antioxidant molecules included in niosomes. Specifically, the studies were conducted to evaluate how the vesicular systems affect the release of the active ingredient and which formulation is most suitable for cutaneous application. Niosomes, composed of Span 20 or Tween 20, were produced through the direct hydration method, and therefore, borate buffer or a micellar solution of poloxamer 188 was used as the aqueous phase. The niosomes were firstly characterized in terms of morphology, dimensional and encapsulation stability. Afterwards, gels based on poloxamer 407 or xanthan gum were compared in terms of spreadability and adhesiveness. It was found to have greater spreadability for gels based on poloxamer 407 and 100% adhesiveness for those based on xanthan gum. The in vitro diffusion of drugs studied using Franz cells associated with membranes of mixed cellulose esters showed that the use of a poloxamer micellar hydration phase determined a lower release as well as the use of Span 20. The thickened niosomes ensured controlled diffusion of the antioxidant molecules. Lastly, the in vivo irritation test confirmed the safeness of niosomal gels after cutaneous application

Ellagic acid containing Nanostructured Lipid Carriers for topical application: a preliminary study

Ellagic acid (EA) is a potent antioxidant substance of natural origin characterized by poor biopharmaceutical properties and low solubility in water that limit their use. The aim of the present study was to develop lipid based nanoparticle formulations able to encapsulate EA for dermal delivery purpose. The EA-loaded nanoparticles were prepared using two different lipid compositions, namely tristearin/tricaprylin (NLC-EA1) and tristearin/labrasol (NLC-EA2). The influence of formulations on size, entrapment efficiency and stability of EA-loaded nanoparticles was investigated. Cryo-TEM and SAXS analysess showed that no morphological differences are evident among all the types of loaded and unloaded NLC. The macroscopic aspect of both NLC-EA1 and NLC-EA2 did not change by time. No difference in size is appreciable between empty and drug-containing NLC, thus the nanoparticle diameter is not affected by the presence EA and in general no variations of the diameters occur during time. The percentage of entrapment efficiency of both EA-loaded nanoparticles was almost quantitative. In addition NLC-EA1 maintain EA stability for almost 2 months, while NLC-EA2 up to 40 days. FRAP assay showed an antioxidant activity around 60% for both the loaded NLC, as compared to the solution. Although both types of NLC are characterized by some toxicity, NLC-EA1 are less cytotoxic than NLC-EA2. Taken together these results demonstrated that the inclusion of EA within NLC could improve the water solubility, allowing for a reduction of the dosage. Moreover, the maintaining of high antioxidant effect and low toxicity were evidenced for both types of NLC-EA

Ethosomes and transethosomes for mangiferin transdermal delivery

Mangiferin is a natural glucosyl xanthone with antioxidant and anti-inflammatory activity, making it suitable for protection against cutaneous diseases. In this study ethosomes and transethosomes were designed as topical delivery systems for mangiferin. A preformulation study was conducted using different surfactants in association with phosphatidylcholine. Vesicle dimensional distribution was monitored by photon correlation spectroscopy, while antioxidant capacity and cytotoxicity were respectively assessed by free radical scavenging analysis and MTT on HaCaT keratinocytes. Selected nanosystems were further investigated by cryogenic transmission electron microscopy, while mangiferin entrapment capacity was evaluated by ultracentrifugation and HPLC. The diffusion kinetics of mangiferin from ethosomes and transethosomes evaluated by Franz cell was faster in the case of transethosomes. The suitability of mangiferin-containing nanovesicles in the treatment of skin disorders related to pollutants was investigated, evaluating, in vitro, the antioxidant and anti-inflammatory effect of ethosomes and transethosomes on human keratinocytes exposed to cigarette smoke as an oxidative and inflammatory challenger. The ability to induce an antioxidant response (HO-1) and anti-inflammatory status (IL-6 and NF-kB) was determined by RT-PCR and immunofluorescence. The data demonstrated the effectiveness of mangiferin loaded in nanosystems to protect cells from damage. Finally, to gain insight into the keratinocytes' uptake of ethosome and transethosome, transmission electron microscopy analyses were conducted, showing that both nanosystems were able to pass intact within the cells

Up-Cycling of Olea europaea L. Ancient Cultivars Side Products: Study of a Combined Cosmetic-Food Supplement Treatment Based on Leaves and Olive Mill Wastewater Extracts

In recent years, a reversal of the global economic framework has been taking place: from the linear model, there has been a gradual transition to a circular model where by-products from the agri-food industry are taken and transformed into value products (upcycling) rather than being disposed of. Olive tree pruning represents an important biomass currently used for combustion; however, the leaf part of the olive tree is rich in phenolic substances, including hydroxytyrosol. Mill wastewater is also discarded, but it still contains high amounts of hydroxytyrosol. In this study, cosmetic and food supplement formulations were prepared using biophenols extracted from leaves and wastewater and were tested in a placebo-controlled study on healthy volunteers using a combined cosmetic and food supplement treatment. A significant improvement in skin health indicators (collagen density, elasticity, etc.) and a 17% improvement against Photo-induced Irritative Stimulus was observed

Chemical Composition and Anti-Candida Activity of Mentha suaveolens Ehrh. Essential Oils Obtained by Different Distillation Processes

A comparative study on essential oils extracted from Mentha suaveolens Ehrh. from Italy is reported. Two extraction procedures were investigated: hydrodistillation and steam distillation, carried out as a continuous and fractionated procedure. Fresh and dried plant material from two harvests was used. The hydrodistillation method yielded a higher amount of essential oil. The dried plant was significantly richer in essential oil per kg of starting plant material. Gas chromatography-mass spectrometry analysis of 112 samples showed that the essential oils belong to the piperitenone oxide-rich chemotype. In addition, piperitenone, p-cymen-8-ol, and limonene were among the most abundant compounds in the different samples. A higher amount of piperitenone oxide was obtained by hydrodistillation, while steam distillation gave a higher percentage of piperitenone and limonene. The essential oils were characterized for their anti-Candida albicans activity; higher potency was observed for the samples rich in piperitenone oxide, with MIC values ranging from 0.39 to 0.78 mg·mL−1 (0.039% and 0.078% p/v). The results of this work provide a deep insight into the methodology of essential oil extraction and the associated chemical variability of M. suaveolens Ehrh. Some of the essential oils are potent against C. albicans and could be considered for potential use in therapy

A Probable Fatal Case of Oleander (Nerium oleander) Poisoning on a Cattle Farm: A New Method of Detection and Quantification of the Oleandrin Toxin in Rumen

Oleander (Nerium oleander) is an ornamental plant common in tropical and sub-tropical regions that is becoming increasingly widespread, even in temperate regions. Oleander poisoning may occur in animals and humans. The main active components contained in the plant are cardiac glycosides belonging to the class of cardenolides that are toxic to many species, from human to insects. This work describes a case of oleander poisoning that occurred on a small cattle farm and resulted in the fatality of all six resident animals. Furthermore, the investigation of the poisonous agent is described, with particular focus on the characterization of the oleandrin toxin that was recovered from the forage and rumen contents. The innovation of this study is the first description of the detection and quantification of the oleandrin toxin by liquid chromatography-high resolution mass spectrometry (LC-HRMS) in rumen

Application of the “in-oil nanoprecipitation” method in the encapsulation of hydrophilic drugs in PLGA nanoparticles

A novel “in-oil nanoprecipitation” method has been previously developed for the nanoincapsulation of water-soluble drugs in poly (D,L-lactide-co-glicolide) (PLGA) and in the present work it was applied to three hydrophilic model-drugs with different characteristics and molecular weight, namely protamine sulphate, sodium diclofenac and N6-ciclopentiladenosine (CPA). Although the same settings were used for all the model-drugs, the drug loading efficiency resulted higher for the protamine (around 93%), intermediate for diclofenac (around 50%) and very low for the CPA (around 7%), in close dependence on chemical-physical characteristics of the drugs. Also particle size resulted strictly model-drug dependent as well as the drug release rate. In the aim to improve the characteristics of the CPA–loaded nanoparticles, the effects of an additional excipient (lauric acid) or the substitution of PLGA with poly (D,L-lactide) polymer (PLA) was investigated by the evaluation of the in vitro drug release and the drug degradation kinetic in human whole blood. The results indicate that the proposed method seems promising for the nanoencapsulation of hydrophilic drugs in hydrophobic polymers and easily modifiable formolecules difficult to be incorporated into polymeric matrix

New class of proteasome 20S inhibitors: a crystallographic and molecular modelling study

In this communication the crystallographic structures of two protesome 20s inhibitors are reported, together with a conformational study of the molecules in the solid state, in vacuum and in a polar environment which is in turn the basis for a docking study of such inhibitors to the crystallographic structure of the proteasome