Considering a growing demand for medicinal/cosmetic products with natural actives, this study focuses on the low-energy nanoemulsions (LE-NEs) prepared via the Phase inversion composition (PIC) method at room temperature as potential carriers for natural oil. Four different red raspberry seed oils (ROs) were tested, as follows: cold-pressed vs. CO₂-extracted, organic vs. non-organic, refined vs. unrefined. The oil phase was optimized with Tocopheryl acetate and Isostearyl isostearate, while water phase was adjusted with either glycerol or an antioxidant hydro-glycolic extract. This study has used a combined approach to formulation development, employing both conventional methods (pseudo-ternary phase diagram − PTPD, electrical conductivity, particle size measurements, microscopical analysis, and rheological measurements) and the methods novel to this area, such as textural analysis and Raman spectroscopy. Raman spectroscopy has detected fine differences in chemical composition among ROs, and it detected the interactions within nanoemulsions. It was shown that the cold-pressed, unrefined, organic grade oil (RO2) with 6.62% saturated fatty acids and 92.25% unsaturated fatty acids, was optimal for the LE-NEs. Textural analysis confirmed the existence of cubic gel-like phase as a crucial step in the formation of stable RO2-loaded LE-NEs, with droplets in the narrow nano-range (125 to 135 nm; PDI ≤ 0.1). The DPPH test in methanol and ABTS in aqueous medium have revealed a synergistic free radical scavenging effect between lipophilic and hydrophilic antioxidants in LE-NEs. The nanoemulsion carrier has improved the biological effect of raw materials on HeLa cervical adenocarcinoma cells, while exhibiting good safety profile, as confirmed on MRC-5 normal human lung fibroblasts. Overall, this study has shown that low-energy nanoemulsions present very promising carriers for topical delivery of natural bioactives. Raman spectroscopy and textural analysis have proven to be a useful addition to the arsenal of methods used in the formulation and characterization of nanoemulsion systems.

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.

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 li-posomes 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), transepi-dermal water loss (TEWL), erythema index (EI) and viscoelas-ticity 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, espe-cially 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 in-vestigated actives incorporated into alkyl polyglucoside emulsi-fier-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.

The aim of this study was to assess and improve the oxidative stability of red raspberry seed oil–RO, a potential topical ingredient derived from food industry by-products, on its own and when incorporated in low energy nanoemulsion (NE). The RO’s oxidative stability was assessed at 5, 25, and 40 °C during one month of storage and expressed in: peroxide value, p-anisidine, and thiobarbituric reactive substances—TBARS value, while for NEs, lipid hydroperoxides and TBARS values were monitored. Both synthetic (butylated hydroxytoluene—BHT and ethylenediaminetetraacetic acid—EDTA), and natural (oregano essential oil—ORE and oak fruit extract—OAK) antioxidants were used. Pure RO and RO with BHT or ORE were stable at 5 °C and 25 °C, but at 40 °C BHT showed only moderate protection, while ORE was prooxidant. NEs prepared with new biodegradable polyglycerol esters-based surfactants, with droplet sizes of < 50 nm and narrow size distribution, showed improved physicochemical stability at room temperature, and especially at 40 °C, compared to NEs with polysorbate 80, which required the addition of antioxidants to preserve their stability. Natural antioxidants ORE and OAK were compatible with all NEs; therefore, their use is proposed as an effective alternative to synthetic antioxidants.

In this study several essential oils (EOs): basil - BA, lemon balm - LB and oregano - OR were incorporated into nanoemulsions (NEs) as prospective carriers for natural and sensitive bioactives. NEs were prepared via the phase inversion composition (PIC) method, which is an energy-efficient cold process. Physicochemical stability of NEs was confirmed by particle size distribution analysis, electrical conductivity and pH value measurements, as well as by optical microscopy observations. The type of EO and the surfactant and oil mix concentration were found to be crucial factors governing the NE properties and stability. Raman spectra of the EOs confirmed main active ingredients and provided detection of interactions with the nanocarrier, which is a novel application of this technique. The antioxidant activity towards DPPH radical in methanol was concentration-dependent with a similar trend for individual oils and oil-loaded NEs (OR> LB> BA). However, the ABTS test in an aqueous medium revealed notable change in the order of activity after EO nanonisation at higher EO concentrations. Overall, it was found that OR-NE was the most effective and stable system, since OR acted as a co-stabiliser in the NE formulation, and its remarkably high antioxidant activity was successfully preserved during 6 months of storage.

Background/Objectives: Nanoemulsions (NEs) are highly promising drug delivery systems that can be made user-friendlier by thickening to nanoemulsion gels (NEGs). However, in order to be regulatory accepted, such a transformation requires systematic understanding of the underlying interactions and stabilization mechanisms, especially when the incorporated active pharmaceutical ingredient may infiltrate the stabilizer layer. Methods: NEs with/without ibuprofen were submitted through direct vs. indirect gelation using three different gelling agents (carbomer 980, xanthan gum, or polyacrylate crosspolymer-6). Multi-technique characterization was employed to demonstrate nanoparticle preservation within the gel networks, a point often neglected when studying nanogels. Results: The nanoemulsion with the most favorable properties (55.07 ± 0.82 nm, PDI 0.075 ± 0.022) was successfully transformed into nanoemulgels with all three gelling agents, both by an indirect and direct approach. The combination of Fourier-transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) revealed complex interactions and electron paramagnetic resonance spectroscopy (EPR)-discerned localization of the small-molecule model drug within the surfactants/co-solvents’ microenvironment, while atomic force microscopy (AFM) successfully visualized nanodroplets, with or without the presence of aggregates originating from the applied gelling agent. Conclusions: A series of complementary techniques confirmed the preservation of nanodroplets after transformation while highlighting the potential of novel polyacrylate crosspolymer-6 to produce robust gel network while effectively increasing zeta potential from −11.07 to −30.5 mV and allowing for satisfactory ibuprofen release from nanoparticles.