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. 2022 Dec 20:17:6447-6465.
doi: 10.2147/IJN.S376750. eCollection 2022.

Neem Oil or Almond Oil Nanoemulsions for Vitamin E Delivery: From Structural Evaluation to in vivo Assessment of Antioxidant and Anti-Inflammatory Activity

Federica Rinaldi #  1 , Patrizia Nadia Hanieh #  1 , Linda Maurizi  2 , Catia Longhi  2 , Daniela Uccelletti  3 , Emily Schifano  3 , Elena Del Favero  4 , Laura Cantù  4 , Caterina Ricci  4 , Maria Grazia Ammendolia  5 , Donatella Paolino  6 , Francesca Froiio  6 , Carlotta Marianecci  1 , Maria Carafa  1
Affiliations

Neem Oil or Almond Oil Nanoemulsions for Vitamin E Delivery: From Structural Evaluation to in vivo Assessment of Antioxidant and Anti-Inflammatory Activity

Federica Rinaldi et al. Int J Nanomedicine. .

Abstract

Purpose: Vitamin E (VitE) may be classified in "the first line of defense" against the formation of reactive oxygen species. Its inclusion in nanoemulsions (NEs) is a promising alternative to increase its bioavailability. The aim of this study was to compare O/W NEs including VitE based on Almond or Neem oil, showing themselves antioxidant properties. The potential synergy of the antioxidant activities of oils and vitamin E, co-formulated in NEs, was explored.

Patients and methods: NEs have been prepared by sonication and deeply characterized evaluating size, ζ-potential, morphology (TEM and SAXS analyses), oil nanodroplet feature, and stability. Antioxidant activity has been evaluated in vitro, in non-tumorigenic HaCaT keratinocytes, and in vivo through fluorescence analysis of C. elegans transgenic strain. Moreover, on healthy human volunteers, skin tolerability and anti-inflammatory activity were evaluated by measuring the reduction of the skin erythema induced by the application of a skin chemical irritant (methyl-nicotinate).

Results: Results confirm that Vitamin E can be formulated in highly stable NEs showing good antioxidant activity on keratinocyte and on C. elegans. Interestingly, only Neem oil NEs showed some anti-inflammatory activity on healthy volunteers.

Conclusion: From the obtained results, Neem over Almond oil is a more appropriate candidate for further studies on this application.

Keywords: C. elegans; HaCaT; O/W nanodispersion; anti-inflammatory activity; healthy volunteers; α-tocopherol.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

None
Graphical abstract
Figure 1
Figure 1
Morphological observations of nanoemulsions by transmission electron microscopy. Upper row: Almond-based NEs; bottom row: Neem-based NEs. (A and D): NEs before sonication (samples A and N); (B and E): Empty NEs after sonication (samples A1 and N1); (C and F): Vit-E loaded NEs (samples A1E and N1E).
Figure 2
Figure 2
SAXS profiles of NEs. (A) Neem-based NEs intensity profiles: unloaded N1 (gray dots), VitE-loaded N1E (black triangles) in log-log scale. (B) Almond-based NEs intensity profiles: unloaded A1 (Orange dots), VitE-loaded A1E (magenta diamonds) in log-log scale. Solid lines are the best fits for the form factors of the particles.
Figure 3
Figure 3
Pyrene spectra. (A) Fluorescence emission spectrum of pyrene. (B) sample spectra.
Figure 4
Figure 4
Time stability of NEs size and charge. (A): Top row: unloaded NEs; bottom row: VitE-loaded NEs. Left column: Neem-based NEs; right column: Almond-based NEs. (B) Chemical time stability of Vitamin E loaded in NEs as compared to free VitE, up to 90 days at room temperature.
Figure 5
Figure 5
Cell viability of human keratinocytes after A1E, A1, N1E or N1 nanoemulsions exposure. HaCaT cells were pretreated with various concentrations (respect to surfactant) of NEs for 24 h. Data are reported as percentages of the control. Data are expressed as means ± standard deviations from at least three independent experiments performed in triplicate. Asterisks indicate statistically significant differences at p ≤ 0.01.
Figure 6
Figure 6
Analysis of oxidative stress responses in transgenic sod-3::GFP nematodes. Median fluorescence intensity of sod-3::GFP worm strain at the stage of 13 days adult fed heat killed OP50 (control) supplemented with (A) A1E, A1, (B) N1E and N1 nanoemulsions at different dilutions. Statistical analysis was evaluated by one-way ANOVA with the Bonferroni post-test; asterisks indicate significant differences (*p<0.01; **p<0.01; ***p<0.01). Bars represent the mean of three independent experiments.
Figure 7
Figure 7
In vivo skin tolerability of the formulation expressed as variation of the erythema index (ΔEI). Results are the mean of three experiments ± standard deviation. Data obtained testing formulation A1, A1E, N1 and N1E were compared to the ones carried out by saline solution. *p < 0.05, **p < 0.01, and ***p < 0.001.
Figure 8
Figure 8
In vivo anti-inflammatory activity of formulations evaluated as their ability to reduce chemically induced skin erythema. Results are expressed as variation of the erythema index (ΔEI) and are the mean of three experiments ± standard deviation. Data obtained testing formulation A1, A1E, N1 and N1E were compared to the ones carried out by saline solution. **p < 0.01, and ***p < 0.001.
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