Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity

Abstract

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. CO 2extracted, 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

Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance

“…Among the available nanoemulsion production methods, the low energy methods performed with minimal energy input (e.g., Phase inversion composition method at room temperature) are highly suitable for natural and thermo-sensitive molecules [ 9 , 15 ]. Methods that are based on the physico-chemical bottom-up approach rely on the release of chemical energy when carefully selected ingredients are mixed in a specific way, leading to surfactant self-assembly and spontaneous formation of small nanodroplets [ 14 , 15 , 30 ].…”

“…Nanoemulsions were prepared according to the phase inversion composition (PIC) method [ 9 , 15 ] by stepwise addition of the water phase to the organic phase (surfactants/cosurfactant and oils) under continuous vortex mixing at 1300 rpm, to obtain a maximum sample volume of 5 to 10 mL. During the optimization phase, the following components were mixed at various ratios: surfactants (P4L and TS), oil phase (EP, red raspberry seed oil and cosurfactants) and water phase (water, glycerol) to detect the minimal SOR and SER necessary to form nanoemulsions with mean droplet sizes < 100 nm and narrow polydispersity index (PDI < 0.15).…”

“…The DPPH assay in methanol was performed similarly to our previous work [ 9 ], with small modifications. Nanoemulsions were tested at several concentrations (10, 30 and 50 µL/mL), while the nanoemulsion solutions in methanol served as blanks.…”

“…Hydro-ethanolic extract from red raspberry fruit was shown to inhibit UVB-induced secretion of matrix metalloproteinase 1 and 3 and inflammatory factors IL-6 and IL-1β, while promoting type I procollagen synthesis, thus exhibiting anti-photoaging effects [ 5 ]. Other types of hydrophilic and lipophilic extracts obtained from berries and from wood waste products (such as oak acorns) also exhibit antioxidant and anti-carcinogenic activity [ 6 , 7 , 8 , 9 , 10 ]. The above-mentioned extracts are rich in bioactives which are usually sensitive to heat, light and air, thus requiring effective carriers and mild processing conditions to preserve their activity.…”

“…Thus, nanoemulsions of the oil-in-water (O/W) type are considered more favorable for skin application due to higher water content, lower skin irritation potential and commercial reasons [ 12 , 13 , 16 ]. Other desirable nanoemulsion features well-suited for topical formulations include pleasant visual appearance, high fluidity and good spreadability on skin surface, while the large surface area of small nanodroplets on the skin leads to improved or controlled penetration of active molecules [ 9 , 17 ].…”