Dermocosmetic emulsions stabilized with lamellar liquid-crystalline phase as a vehicle for lactobionic acid - colloidal structure, efficacy and safety assessments

Увод Алфа-хидрокси киселине (енг. alphahydroxyacids, AHAs) представљају групу активних супстанци у препаратима на граници козметички производ – дерматолошки лек, тзв. дермокозметичким производима/козметоцеутицима. Поред доказане ефикасности и мултифункционалности, AHAs показују неповољан безбедносни профил на кожи, нарочито уколико су инкорпориране у неадекватне носаче. Тврди се да је представник новије генерације AHAs, првенствено лактобионска киселина (ЛК), безбеднија за примену на кожи. Савремена козметологија тежи формулацији ефикасних, нешкодљивих, естетски и еколошки прихватљивих производа. Фокус је посебно на природним сурфактантима као помоћним састојцима емулзионих носача, нарочито на шећерним ПАМ – алкил полиглукозидима (АПГ). Нема података о компатибилности ЛК и АПГ; информације о ефикасности и безбедности ЛК у емулзијама стабилисаним АПГ мешаним емулгаторима (сличним реалним дермокозметичким/ дермофармацеутским системима) оскудне су и нису добијене у складу са релевантним захтевима актуелних законских смерница – Уредбе EU 1223/2009 о козметичким производима. Циљ истраживања Циљ истраживања ове докторске дисертације био је: 1) формулација физички стабилних мултикомпонентних емулзија стабилисаних АПГ мешаним емулгаторима различитих дужина алкил ланаца, са и без ЛК; 2) процена колоидне структуре ових емулзија; 3) процена и поређење њихове безбедности и ефикасности на кожи у складу са захтевима важећих европских прописа. Тачније, свеобухватна испитивања спроведена су ради процене погодности емулзија са различитим АПГ мешаним емулгаторима да буду носачи за киселу и хигроскопну ЛК, као и ради одређивања и поређења ефикасности и безбедности 6% ЛК у односу на исту концентрацију гликолне киселине (ГК), представника старије генерације AHAs. Крајњи циљ била је свеобухватна процена погодности употребе ЛК и АПГ као алтернативних састојака дермокозметичких производа...Introduction Alphahydroxyacids (AHAs) represent the class of actives in border-line topical products – cosmeceuticals/dermocosmetics. Although AHAs exhibit multiple benefits to the skin, the application of cosmeceuticals containing "old generation" AHAs representatives is often limited due to their compromising safety profile, particularly when they are incorporated into unsuitable vehicle. There is a growing need for research into new skin- and environmentally-friendly actives and surfactants in the field of cosmetics; it is claimed that "new generation" AHAs, particularly lactobionic acid (LA), could be used as safer alternatives to "old" ones, while natural alkyl polyglucoside (APG) emulsifiers are in the focus of current researches as well. There is a lack of studies, complying with the Regulation (EC) No 1223/2009, which clarify the efficacy and safety of topical application of LA per se or LA incorporated into APG-based emulsions. Aim The aim of this study was to 1) formulate physically stable emulsions, similar to real pharmaceuticals/dermocosmetic vehicles, with or without LA, based on different mixed APG surfactants varying in the alkyl chain length; 2) assess the colloidal structure of the emulsions; 3) assess the main aspects of the efficacy and safety of investigated dermocosmetic APG-based emulsions containing LA, and compare them with the same aspects of APG-based emulsions containing glycolic acid (GA, old generation AHA). The appropriate tests were performed according to the requirements of the EC legislation, in order to investigate both LA and APGs as alternative cosmeceutical compounds..

Noviji prirodni šećerni emulgatori namenjeni izradi nosača za dermatološke lekove i kozmetički aktivne supstance - ispitivanje bezbednosti i efikasnosti

Despite a large number of different vehicles available nowadays, conventional emulsion systems remain one of the most commonly used for cosmetic and dermatological preparations. Popularly labelled as skin- and environmentally-friendly, alkyl polyglucoside (APG) sugar-based emulsifiers have attracted considerable interest with regard to their dermatological properties, since irritation potential of commonly used emulsifiers could affect the functionality and safety of dermopharmaceutics. The aim of this study was to promote the emulsion based on C16/18 APG as a prospective vehicle for topical drugs and cosmetic actives assessing the safety for use and skin hydration capacity. In accordance with the requirements of newer legislation in vitro, acute skin irritation test was performed using cytotoxicity assay on artificial skin. The results were compared with in vivo data obtained by measuring the skin biophysical parameters, such as: stratum corneum hydration (SCH), erythema index (EI), and transepidermal water loss (TEWL). Parameters were measured prior to (baseline values) and upon cessation of a 24-h occlusive treatment in 14 healthy human volunteers. In vivo moisturizing capacity of the emulsions was assessed in 16 healthy volunteers in a long-term trial measuring of SCH. This study showed, investigating the most frequently used APG, that emulsions based on these emulsifiers could probably be promoted as safe cosmetic/ dermopharmaceutical vehicles. Prospective safety for human use with the correlation between in vivo and in vitro findings was shown. In addition, the investigated vehicle per se showed an excellent skin moisturizing capacity which is essential in maintaining healthy skin, but also in improving dermatitis, which follows most pathological skin conditions.Emulzije su najčešće korišćeni nosači u izradi kozmetičkih proizvoda i dermatoloških lekova. Emulgatori, obavezni sastojci emulzija, mogu da poseduju visok potencijal da iritiraju kožu i oštećuju njenu barijeru. Nasuprot konvencionalnim, alkil poliglukozidi (APG) kao noviji, blagi, biodegradabilni emulgatori, danas privlače veliku pažnju. Smatra se da, osim što ne iritiraju, pokazuju dodatne pozitivne efekte pri lokalnoj aplikaciji kao što je vlaženje kože. Cilj studije bio je ispitivanje emulzija stabilisanih jednim od najčešće korišćenih C16/18 APG, i to u smislu bezbednosti za upotrebu i potencijala za hidrataciju kože. U skladu sa najnovijom zakonskom regulativom u ovoj oblasti, potencijal za lokalnu iritaciju određen je in vitro testom citotoksičnosti na veštačkoj koži, kao i in vivo merenjem biofizičkih parametara kože na humanim dobrovoljcima: električna kapacitivnost (SCH), eritema indeks (EI) i transepidermalni gubitak vode (TEWL). Merene su bazalne i vrednosti parametara 24h nakon aplikacije uzorka okluzijom. Kapacitet uzorka da efikasno i produženo hidratiše kožu određivan je in vivo merenjem parametra SCH nakon jednokratne aplikacije. Ispitujući emulzije stabilisane jednim od najčešće korišćenih APG, studija je pokazala da se ovi emulgatori verovatno mogu smatrati bezbednim u izradi kozmetič- kih/dermofarmaceutskih nosača, pri čemu su rezultati in vivo i in vitro ispitivanja bili su u međusobnom skladu. Nije registrovan iritacioni potencijal korišćenog APG, inače čest problem pri upotrebi konvecionalnih emulgatora starijih generacija, a pokazan je odličan potencijal emulzija sa C16/18 APG za efikasnu i prolongiranu hidrataciju. Poslednje može biti od velikog značaja u tretmanu zdrave, ali naročito kože zahvaćene dermatitisom koji je pratilac većine patoloških stanja kože

Effect of variable frequency electromagnetic field on deposit formation in installations with geothermal water in Sijarinjska spa (Serbia)

In this paper we have examined the effect of variable frequency electromagnetic field generated with a homemade device on deposit formation in installations with geothermal water from Sijarinjska Spa. The frequency alteration of the electromagnetic field in time was made by means of the sinusoidal and saw-tooth function. In laboratory conditions, with the flow of geothermal water at 0.015 l/s and temperature of 60 °C for 6 hours through a zig-zag glass pipe, a multiple decrease of total deposit has been achieved. By applying the saw-tooth and sinusoidal function, the decrease in contents of calcium and deposit has been achieved by 8 and 6 times, respectively. A device was also used on geothermal water installation in Sijarinjska Spa (Serbia), with the water flow through a 1'' diameter non-magnetic prochrome pipe at 0.15 l/s and temperature of 75 °C in a ten-day period. A significant decrease in total deposit and calcium in the deposit has also been achieved

Evaluation of in vivo effects on surfactant-irritated human skin, antioxidant properties and phenolic composition of five Ericaceae species extracts

Arbutus unedo, Bruckentalia spiculifolia, Calluna vulgaris, Erica arborea and Erica carnea possess strong antioxidant activity and they are traditionally used for the treatment of various skin diseases. The present study investigated the total phenylpropanoid content, antioxidant properties and phenolic composition of dry leaf ethanol extracts of these species. Furthermore, the in vivo effects of gels, each containing 2% of a single extract were tested on the artificially irritated human skin using the objective methods of skin biophysical measurements (erythema index (EI), pH of the skin and electrical capacitance (EC) as a measure of skin hydration level were assessed). In total, 13 components were identified by RP-HPLC coupled with DAD detection; quercitrin, quercetin 3-O-glucoside and gallic acid were detected in all investigated samples while chlorogenic acid and quercetin were present in 4 samples. Regarding the in vivo study, all investigated gels significantly decreased the skin irritation level and reversed the pH of the skin disturbed by preirritation, while results were contradictory regarding skin hydration measurements. In conclusion, the assessed in vivo topical effects of investigated extracts matched well with their phenylpropanoid content as well as with assessed antioxidant activities

Matične ćelije alpske ruže, skvalen maslinovog ulja i prirodni alkil-poliglukozidni emulgator - da li su odgovarajući sastojci kremova za vlaženje - in vivo efikasnost na zdravoj i koži iritiranoj natrijum lauril sulfatom?

Background/Aim. Since skin moisturization may be achieved by both actives and chosen carrier, plant stem cells, squalene and natural alkyl polyglucoside emulsifier may be potential components of contemporary cosmetic products. The aim of the study was in vivo evaluation of the skin irritation potential and the efficacy of Alpine Rose stem cells incorporated into liposomes and olive oil squalene as ingredients of moisturizing creams, with respect to the novel emulsifier used for creams' stabilization. Methods. With the employment of noninvasive skin biophysical measurements, skin hydration (EC), transepidermal water loss (TEWL), erythema index (EI) and viscoelasticity were measured on 76 healthy volunteers. In the first phase, skin irritation after a 24-hour occlusion and the long-term efficacy of creams (a 21-day study) on healthy skin were evaluated. Phase II of the study focused on the cream efficacy assessment after a 6-day treatment of sodium lauryl sulfate-irritated skin. Results. After a 24-hour occlusion, there were no significant changes in the EI for any tested sample. In the second phase of the study, the EI was not significantly altered for the cream containing squalene, while the application of all active samples resulted in a significant reduction of TEWL. In both phases of the study an EC increase was recorded, especially for the squalene-containing cream. Conclusion. Due to the lack of skin irritation and skin barrier impairment along with the marked hydration effect, it could be said that the investigated actives incorporated into alkyl polyglucoside emulsifier-stabilized creams may be safely applied as ingredients for "tailor-made" cosmetic moisturizers intended for normal and dry skin care, whereas olive oil squalene could be used for the treatment of irritated or sensitive skin as well.Uvod/Cilj. S obzirom na to da vlaženje kože može biti postignuto izborom kako aktivnih supstanci, tako i odgovarajućeg nosača, biljne matične ćelije, skvalen i prirodni alkil poliglukozidni emulgator mogu biti potencijalni sastojci savremenih kozmetičkih proizvoda. Cilj ovog rada bio je in vivo procena iritiranog potencijala i efikasnosti matičnih ćelija alpske ruže dodatih u liposome i skvalena maslinovog ulja, kao sastojaka vlažećih krema, imajući u vidu nov emulgator koji je korišćen za njihovu stabilizaciju. Metode. Upotrebom neinvazivnih metoda zasnovanih na biofizičkim merenjima na koži, kod 76 zdravih dobrovoljaca mereni su: hidratacija kože (EC), transepidermalni gubitak vlage (TEWL), eritema indeks (EI) i viskoelastičnost kože. U prvoj fazi studije vršena je procena iritacije kože nakon 24-h okluzije, kao i procena efikasnosti krema nakon primene na zdravoj koži dobrovoljaca u trajanju od 21 dana. Druga faza studije bila je bazirana na proceni efikasnosti krema nakon 6-dnevnog tretmana kože prethodno iritirane natrijum-lauril-sulfatom. Rezultati. Nakon 24-h okluzije nije bilo značajne promene vrednosti EI ni kod jednog ispitivanog krema. U drugoj fazi studije, krem sa skvalenom nije značajno uticao na promenu vrednosti EI, dok je primena svih aktivnih krema dovela do značajnog sniženja vrednosti TEWL. U obe faze studije zabeležen je porast EC, naročito nakon primene krema koji sadrži skvalen. Zaključak. Uzevši u obzir odsustvo nadraženosti kože i narušavanja kožne barijere, kao i porast hidratacije površinskog sloja kože, može se reći da se ispitivane aktivne supstance ubačene u kreme stabilizovane alkil-poliglukozidnim emulgatorom mogu bezbedno koristiti kao komponente tzv. "skrojenih" kozmetičkih ovlaživača namenjenih za negu zdrave i suve kože, dok se skvalen maslinovog ulja može koristiti i za negu iritirane i osetljive kože

Polyglycerol ester-based low energy nanoemulsions with red raspberry seed oil and fruit extracts: Formulation development toward effective in vitro/in vivo bioperformance

This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions were obtained via phase inversion composition (PIC) method at room temperature by dilution of microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic, rheological and Differential Scanning Calorimetry (DSC) investigations. The results have shown that the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet size (Z-ave: 50 to 70 nm, PDI value ≤ 0.1). The highest antioxidant activity (~92% inhibition of the DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles and significant improvement in skin hydration during 2 h after application for all nanoemulsions. Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin protection and hydration

THE INFLUENCE OF POLAR AND NON-POLAR EMOLLIENTS ON THE STRUCTURE AND SKIN MOISTURIZING POTENTIAL OF THE EMULSIONS STABILIZED BY MIXED EMULSIFIER

The appropriate moisture content in the stratum corneum, as a superficial layer of the epidermis, provides softness and flexibility of the skin in different environmental conditions, and maintaining of skin humidity is very important in dermatology and dermocosmetology. In this paper, we investigated the skin moisturizing potential after a single application and structure of the emulsion of o/w type, stabilized by mixed emulsifier glycerylmonostearate self-emulsifying (GMSse), which contained polar emollients (PEG-7 glicerylcocoate and myristyl myristate) and non-polar emollient (liquid paraffin), in a concentration of 10% (emulsions E1-E3, respectively). The emulsion structure was investigated by polarization microscopy, and the presence of different anisotropic structure was observed. The moisturizing potential after a single application and skin pH were investigated by skin bioengineering. Emulsions with polar emollients (E1 and E2) showed a statistically significant increase in skin moisture content after 30 minutes; 300 min after applications it did not exist; emulsion with a non-polar emollient (E3) showed significant moisturizing potential after 30 min and after 300 min probably as a consequence of occlusion. Nature and polarity of emollients affected the structure and properties of emulsions stabilized by anisotropic structures, and also the moisturizing level and pH of the skin immediately after their application

Two alkyl polyglucoside natural surfactants varying in chain length in stabilization of lactobionic acid containing emulsions: physicochemical characterization and in vitro irritation potential assessment

There is a growing need for research into new skin and environmentally-friendly actives and surfactants in the field of cosmetics. This paper focuses on different natural alkylpolyglucoside (APG) emulsifiers (cetearyl alcohol and coco glucoside; arachidyl behenyl alcohol and arachidyl glucoside), which can form lyotropic liquid crystals, in order to promote them as cosmetic excipients. APG-based emulsions as carriers for extremely hygroscopic and acidic cosmetic active, lactobionic acid (LA), belonging to alpha-hydroxy acids (AHAs) were also studied. In the first part of the study, physicochemical properties (assessed by rheology, polarization microscopy and pH and conductivity measurements) and in vitro safety profile (skin irritation test using a cytotoxicity assay) of vehicles were determined in order to compare and estimate their applicability as cosmetic excipients. In the second part, the same methods were conducted in order to establish how those emulsions perform as carriers for different percents of LA. The study showed that both vehicles based on different APGs could be promoted as cosmetic excipients. Either of the APG based emulsions could be vehicles for 6% LA. Cetearyl alcohol and coco glucoside, more hydrophillic emulsifier, is acceptable carrier for 10% LA due to better cytotoxicity profile. The importance of a better cytotoxicity profile without neglecting satisfying physical stability for cosmetic formulations was emphasized

Stability, antioxidant activity, in vivo safety and efficacy of creams with standardized wild apple fruit extract: a comparison of conventional and biodegradable emulsifiers

Objective The aim of the study was in vitro and in vivo characterization of cosmetic cream with 6% of standardized wild apple fruit extract, stabilized by conventional non-ionic emulsifier-CEW, in order to determine the influence of emulsifiers (conventional vs. biodegradable) on the characteristics of creams and their effects on the skin. Methods Organoleptic and physico-chemical (pH values and electrical conductivity) analysis was performed, determination of fruit acids-FAs content (using HPLC analysis) and estimation of its antioxidant activity-AA (using DPPH test) during 180 days. In vivo study included following examinations: screening of safety profile (after creams application under occlusion during 24 h at human skin); skin moisturizing potential, transepidermal water loss-TEWL, skin pH after 28 days of cream application and hypopigmentation efficacy 7 days of cream application at artificially induced skin hyperpigmentation. Results Investigated cosmetic cream-CEW showed satisfactory organoleptic, physico-chemical characteristics, stability, FAs content (0.13%) and AA (19.25 +/- 0.67 %RSC) after preparation, which remained unchanged over the study period. In vivo investigation revealed absence of skin irritation after CEW's application under occlusion. An increase of skin moisturization (after 14 days Delta EC was 18.52 +/- 11.51 and after 28 days of applications 16.52 +/- 9.36) during 28 day-study, with unchanged TEWL and skin pH values was shown. Decrease of melanin index was revealed, too (after 7 days Delta MI was -31.40 +/- 16.50). Conclusion Cosmetic cream stabilized by conventional emulsifier showed better antioxidant potential and weaker moisturizing and hypopigmentation effects related to the cream with same composition but stabilized by biodegradable emulsifiers. Based on all mentioned above, investigated cosmetic cream might be considered for potential use as modern, stable, safe and efficient cosmetic product in the prevention and/or treatment of oxidative stress-related skin changes and/or damages, for moisturization of dry, even irritated skin as well as for lightening of hyperpigmented skin

Does lactobionic acid affect the colloidal structure and skin moisturizing potential of the alkyl polyglucoside-based emulsion systems?

Moisturizing creams are the most prescribed products in dermatology, essential in maintaining healthy skin as well as in the topical treatment of some diseases. The irritation potential of commonly used emulsifiers and moisturizing ingredients, but also their mutual interactions, could affect the functionality and safety of those dermopharmaceutics. The aim of this study was to promote moisturizing alkyl polyglucoside (APG)-based emulsion as vehicle for lactobionic acid (LA), advantageous representative of the alphahydroxyacids (AHAs)-multifunctional moisturizers, assessing the safety for use (in vitro acute skin irritation test using cytotoxicity assay compared with in vivo data obtained using skin bioengineering methods) and in vivo moisturizing capacity (bioengineering of the skin). In order to investigate possible interactions between APG mild natural emulsifier-based emulsion and LA, a deeper insight into the colloidal structure of the placebo and the emulsion with LA was given using polarization and transmission electron microscopy, rheology, thermal and texture analysis. This study showed that APG-based emulsions could be promoted as safe cosmetic/dermopharmaceutical vehicles and carriers for extremely acidic and hygroscopic AHA class of actives (specifically LA); prospective safety for human use of both APG and LA with the correlation between in vivo and in vitro findings was shown. However, it was revealed that LA strongly influenced the colloidal structure of the emulsion based on APGs and promoted the formation of lamellar structures which reflects onto the mode of water distribution within the cream. The advantageous skin hydrating potential of LA-containing emulsion vs. placebo was unlikely to be achieved, pointing that emulsions stabilized by lamellar liquid crystalline structures probably are not satisfying carriers for highly hygroscopic actives in order to reach the full moisturizing potential. Safe and effective use on dry skin is presumed