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. 2021 Aug 24;14(9):837. doi: 10.3390/ph14090837

Table 2.

Phenolic compounds, encapsulated in lipid-based nanosystems for dermal. application.

Main Class Active Agent Technological/Biopharmaceutical Issue Lipid-Based Nanosystem/
Lipid Carrier		 Obtained Results References
Simple phenols and derivatives Hydroquinone Tendency to oxidation; hydrophilic structure hindering its topical application;
side-effects due to systemic
absorption		 SLNs/Precirol® ATO5

  • High hydroquinone encapsulation (app.90%);

  • long-standing physico-chemical stability;

  • enhanced skin accumulation

 [311]
Arbutin Highly hydrophilic compound;
limited skin permeation		 Liposomes/
Soybean phosphatidylcholine; cholesterol

  • Increased skin whitening efficacy;

  • Improved arbutin deposition in epidermis/dermis

 [312,313]
Thymoquinone
(benzo-quinone)		 Thermo/photosensitivity;
hydrophobicity		 Liposomes/
Phospholipon 90H®; cholesterol

  • Improved anti-inflammatory action compared to plain solution;

  • enhanced stability against degradation;

  • increased skin permeation

 [314]
Protocatechuic acid;
Ethyl protocatechuate (phenolic acid and derivative)		 Sparingly hydrosolubilty (1:50);
skin irritating properties;
photosensitivity		 SLNs/
Precirol ATO®5;
NLCs/
Miglyol®810 N: Precirol ATO®5 3:7

  • NLCs are the superior nanosystem concerning PDI and cell viability results compared to SLNs;

  • minimized skin irritation potential of protocatechuic acid; ensured UVB protection;

  • controlled release profile of phenolic acids without systemic exposure

 [315,316]
Ferulic acid
(phenolic acid)		 Poor water solubility;
low stability		 Nanoemulsion/
Isostearyl isosearate

  • Improved solubility and permeability of ferulic acid;

  • significant antioxidant effect

 [317]
Caffeic acid (hydroxyl-cinnamic acid) Limited skin permeation Liposomes/
egg phosphatidyl-choline;
cholesterol

  • High entrapment efficiency values (70%);

  • improved penetration compared to free caffeic acid;

  • preserved antioxidant activity

 [318]
Eugenol
(Clove oil);
(phenylpropene)		 Predisposition to oxidation SLNs/Stearic acid, Compritol®

  • Development of eugenol loaded SLNs incorporated in carbopol hydrogel;

  • improved eugenol deposition in epidermis, compared to reference formulation;

  • achieved controlled release profile;

  • sufficient occlusive properties

 [319]
Flavanoids Naringin
(flavanone)		 Limited aqueous solubility;
poor oral bioavailability		 Liposomes/
Epikuron-200; cholesterol,
Tween 80

  • Improved skin deposition;

  • high encapsulation efficiency (99%);

  • very good physical stability

[320]
Hesperidin
(flavanone glycoside)		 Poor aqueous solubility and bioavailability NLCs/
Cupuaçu butter, buriti oil

  • High encapsulation efficiency (96%);

  • sufficient physical stability;

  • noncytotoxic effect on melanoma cell lines

[321]
Isoflavone-aglycon-rich fraction (genistein, daidzein, glycitein) Limited aqueous solubility Nanoemulsion/
Egg lecithin (Lipoid E-80®), medium-chain triglycerides

  • Improved aqueous solubility;

  • development of nanoemulsion/hydrogel;

  • achieved active agent deposition in stratum corneum, epidermis and dermis (highest)

 [322]
Anthraquinones Aloe -emodin Hydrophobic compound, crystallizes in water Liposomes/
Hydrogenated soybean phosphatidyl-choline, cholesterol

  • Improved skin permeation;

  • low cytotoxicity

 [323]
Naphthoquinones Vitamin K1 (phylloquinone) Highly lipophilic compound;
photosensitivity		 Liposomes/
Soy phosphatidyl-choline, α-tocopherol

  • Elaboration of liposomal aqueous dispersion applied by nebulization;

  • Improved aqueous solubility;

  • increased deposition in epidermis and dermis compared to ointment formulation

 [324]
Xanthones Mangiferin Poor water solubility (0.111 mg/mL);
low bioavailability		 Nanoemulsion/
Almond oil, Lipoid ®S75

  • Enhanced permeation;

  • anti-inflammatory effect;

  • reduced edema and leukocyte infiltration

 [325]
Stilbenes Resveratrol Low aqueous
solubility;
photosensitivity		 SLNs/
Compritol 888 ATO
NLCs/
Compritol 888 ATO; Miglyol oil

  • Resveratrol loaded NLCs were superior to SLNs with respect to entrapment efficiency values, skin penetration, accumulation in dermis

 [326,327]
Pterostilbene None;
favorable characteristics compared to resveratrol (i.e., increased lipophilicity, membrane permeability and bioavailability)		 Liposomes/
Lecithin

  • Effectively prevents UVB-radiation induced skin carcinogenesis in mice

 [328]
Tannins Ellagic acid Low aqueous solubility and permeability NLCs/
Tristearin, Miglyol oil

  • Improved solubility;

  • high antioxidant activity

 [329]