'All-natural' anti-wrinkle emulsion serum with Acmella oleracea extract: A design of experiments (DoE) formulation approach, rheology and in vivo skin performance/efficacy evaluation.

OBJECTIVE: The growing consumers' preferences and concerns regarding healthy ageing, youthful skin appearance, environmental protection and sustainability have triggered an ever-increasing trend towards natural, eco-friendly and ethically sourced anti-ageing products. Accordingly, this paper describes design and evaluation of novel, safe, effective and high-quality emulsion serums, completely based on ingredients of natural origin, intended for improving facial fine lines and wrinkles. METHODS: Model formulations, stabilized by an innovative glycolipid mixed emulsifier (lauryl glucoside/myristyl glucoside/polyglyceryl-6 laurate) and containing Acmella oleracea extract as a model anti-ageing active, were prepared by cold process and fully assessed regarding their rheological behaviour (continuous rotational and oscillatory tests) and physical stability (dynamic-mechanical thermoanalysis - DMTA test). To study and optimize the simultaneous influence of varied formulation factors (emollients and emulsifier concentrations) on critical rheological attributes of the developed serums, a central composite design within 'design of experiments' approach was employed. The general skin performance - preliminary safety and anti-wrinkle efficacy of selected model serum, was evaluated in human volunteers, by employing several objective, non-invasive bioengineering techniques. RESULTS: Rheological characterization revealed favourable shear-thinning flow behaviour with yield point, and dominating elastic character (storage modulus G' > loss modulus G") in both amplitude and frequency sweeps, which together with relatively small structural change obtained in DMTA test indicated overall satisfying rheological and stability properties of formulated serums. From the established design space, and taking into account formulation cost and carbon footprint, promising model serum (desired/optimal apparent viscosity, yield point and loss factor, rather small and constant structural change), containing 15% of emollients and 1% of emulsifier, was chosen for in vivo evaluations. Screening of skin irritation effects revealed the absence of potential irritancy of investigated serum, suggesting overall satisfying skin tolerability/preliminary safety. Silicone skin replica image analysis demonstrated noticeable reduction/improvement in all measured skin wrinkle parameters after only 2 weeks of test serum application in periorbital and perioral areas, indicating its rapid and beneficial effects on the facial expression lines and wrinkles. CONCLUSION: Altogether, the results corroborate the promising potential of the developed Acmella oleracea extract-loaded emulsion serum as safe, effective and non-invasive natural anti-wrinkle product.

OBJECTIF: Les préférences et les préoccupations croissantes des consommateurs concernant le vieillissement sain, l'apparence jeune de la peau, la protection de l'environnement et la durabilité ont déclenché une tendance toujours croissante vers des produits anti-âge naturels, respectueux de l'environnement et éthiques. En conséquence, ce document décrit le plan et l'évaluation de nouveaux sérums d'émulsion sûrs, efficaces et de haute qualité, entièrement basés sur des ingrédients d'origine naturelle, destinés à améliorer les ridules et rides du visage. MÉTHODES: Des formulations modèles stabilisées par un émulsifiant mixte glycolipide innovant (lauryl glucoside/myristyl glucoside/polyglycéryl-6 laurate) et contenant de l'extrait d'Acmella oleracea comme anti-vieillissement actif de modèle, ont été préparées par un procédé à froid et ont été pleinement évaluées en ce qui concerne leur comportement rhéologique (tests de rotation continue et examens oscillatoires) et stabilité physique (analyse thermomécanique dynamique - DMTA). Pour étudier et optimiser l'influence simultanée de facteurs de formulation variés (concentrations d'émollients et d'émulsifiants) sur les attributs rhéologiques critiques des sérums développés, une conception composite centrale dans le cadre d'une approche « conception d'expériences ¼ a été employée. Les performances cutanées générales - sécurité préliminaire et efficacité antirides du sérum du modèle sélectionné ont été évaluées chez des sujets humains volontaires, en utilisant plusieurs techniques de bio-ingénierie objectives et non invasives. RÉSULTATS: La caractérisation rhéologique a révélé un comportement favorable du débit de cisaillement avec une limite de rendement et une domination du caractère élastique (modulus de stockage G' > module de perte G) dans les balayages d'amplitude et de fréquence, qui, avec un changement structurel relativement faible obtenu dans l'analyse DMTA, a indiqué des propriétés rhéologiques et de stabilité satisfaisante globales des sérums. A partir de l'espace de conception établi, et en tenant compte du coût de composition et de l'empreinte carbone, un sérum modèle prometteur (viscosité apparente souhaitée/optimale, seuil de rendement et facteur de perte, changement structurel assez faible et constant), contenant 15 % d'émollients et 1 % d'émulsifiant, a été choisi pour les évaluations in vivo. Le dépistage des effets d'irritation cutanée a révélé l'absence d'irritation potentielle du sérum expérimental, suggérant une tolérance cutanée/une sécurité préliminaire globalement satisfaisante. L'analyse de l'image de la réplique cutanée en silicone a démontré une réduction/amélioration notable de tous les paramètres de rides cutanées mesurés après seulement deux semaines d'application du sérum test dans les zones périorbitaires et péribuccales, indiquant ses effets rapides et bénéfiques sur les lignes d'expression et les rides du visage. CONCLUSION: Au total, les résultats corroborent le potentiel prometteur du sérum d'émulsion à base d'extrait d'Acmella oleracea développé comme un produit anti-rides naturel sûr, efficace et non invasif.

Parenteral nanoemulsions of risperidone for enhanced brain delivery in acute psychosis: Physicochemical and in vivo performances.

This work aimed to deepen the lately acquired knowledge about parenteral nanoemulsions as carriers for brain delivery of risperidone, a poorly water-soluble antipsychotic drug, through establishing the prospective relationship between their physicochemical, pharmacokinetic, biodistribution, and behavioral performances. For this purpose, two optimized risperidone-loaded nanoemulsions, stabilized by lecithin or lecithin/polysorbate 80 mixture, and costabilized by sodium oleate, were produced by high-pressure homogenization. The characterization revealed the favorable droplet size, narrow size distribution, high surface charge, with proven stability to autoclaving and long-term stability for at least one year at 25±2°C. Pharmacokinetic and tissue distribution results demonstrated improved plasma, liver, and brain pharmacokinetic parameters, resulting in 1.2-1.5-fold increased relative bioavailability, 1.1-1.8-fold decreased liver distribution, and about 1.3-fold improved brain uptake of risperidone active moiety following intraperitoneal administration of nanoemulsions relative to solution in rats. In behavioral study, investigated nanoemulsions showed pronounced reduction in basal and, more pertinently, amphetamine-induced locomotor activity in rats, with an early onset of antipsychotic action, and this effect lasted at least 90min after drug injection. Together, these findings corroborate the applicability of parenteral nanoemulsions as carriers for enhanced brain delivery of risperidone, further suggesting their promise in acute psychosis treatment or other emergency situations.

Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles for two poorly water-soluble drugs: physicochemical characterization and in vivo skin performance.

Two types of biocompatible surfactants were evaluated for their capability to formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly water-soluble model drugs differing in properties and concentrations: alkyl polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated surfactants (glycereth-7-caprylate/ caprate and polysorbate 80). Phase behavior, structural inversion and microemulsion solubilization potential for sertaconazole nitrate and adapalene were found to be highly dependent on the surfactants structure and HLB value. Performed characterization (polarized light microscopy, pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a formulation containing glycereth- 7-caprylate/caprate as suitable for incorporation of both drugs, whereas alkyl polyglucoside-based systems did not exhibit satisfying solubilization capacity for sertaconazole nitrate. Further, monitored parameters were strongly affected by sertaconazole nitrate incorporation, while they remained almost unchanged in adapalene-loaded vehicles. In addition, results of the in vivo skin performance study supported acceptable tolerability for all investigated formulations, suggesting selected microemulsions as promising carriers worth exploring further for effective skin delivery of model drugs.