TABLE 2.
A summary of different types of nanoparticles, the loaded cargo, particle size, and advantages of drug encapsulation in melsma management.
| Nanocarrier | Drug | Drug percentage | Particle size | Entrapment efficiency (%EE) and loading capacity (%LC) | Advantages/Outcome | Reference(s) |
|---|---|---|---|---|---|---|
| SLNs a | Hydroquinone | 2% | 86 nm | %EE: 89.50% ± 4.50% | • Enhanced skin deposition | Ghanbarzadeh et al. (2015a), Salimi and Hajiani (2018) |
| • Higher drug accumulation within skin layers | ||||||
| %LC: 11.20% ± 1.30% | ||||||
| • Reduced systemic absorption | ||||||
| Kojic acid | 0.2% | 156.97 ± 7.15 nm | %EE: 59.02% ± 0.74% | • Improve dermal delivery of kojic acid | Khezri et al., 2020a | |
| %LC: 14.75% ± 1.63% | ||||||
| NLCs b | Hydroquinone | 5% | 393.30 ± 28.23 nm | %EE: 22.13% ± 2.66% | • Enhanced drug stability | Wu et al. (2017) |
| • Diminished skin irritation | ||||||
| LC: 19.28% ± 4.77% | • Improved skin penetration | |||||
| • Enhanced protection against UVA/UVB radiation | ||||||
| Azelaic acid | NA c | 81.57 ± 9.6 nm | NA | • Targeted drug delivery to the melanocytes | Kumari et al. (2015) | |
| • Improved effectiveness | ||||||
| • Delayed drug release | ||||||
| • Reduced adverse drug reactions effects due to the gradual exposure of the skin with lower concentrations of azelaic acid | ||||||
| Liposomes | Azelaic acid & 4-n-butylresorcinol and retinol | NA | NA | NA | • Reduced melasma severity | Kusumawardani et al. (2019) |
| Hydroquinone | 4% | 126 nm | NA | • Preserved therapeutic effectiveness | Taghavi et al. (2019a) | |
| Azelaic acid | 20% | 500 nm | %EE: 85.73% | • Maintain therapeutic efficacy | Ayumi et al., 2019; Akl (2022b), Pasca et al. (2022) | |
| • Lower recurrence rate | ||||||
| • Fewer adverse reactions | ||||||
| Kojic acid and hydroquinone | NA | 10 µm | NA | • High encapsulation efficiency | Divanbeygikermani et al. (2018), Kusumawardani et al. (2019) | |
| • High protection against photodegradation and oxidation of hydroquinone | ||||||
| • Prolonged drug release pattern | ||||||
| Arbutin and coumaric acid | 0.05% arbutin and 0.05% coumaric acid | 569.67 nm | %EE: 91.08% for arbutin and 80.92% for coumaric acid | • Improved drug stability | Taghavi et al. (2019a), Huang et al. (2019) | |
| • Enhanced drug solubility | ||||||
| • Sustained drug release | ||||||
| Arbutin | 4% | 179.9–212.8 nm | %EE: 17.6% ± 1.38% | • Maintain therapeutic efficacy | Wen et al. (2006b) | |
| Tranexamic acid | 5% | 126 nm | NA | • A significant reduction in melasma area and severity index | Banihashemi et al. (2015b) | |
| • No serious adverse drug reaction | ||||||
| Resulted in omparative clinical responses to hydroquinone 4% as an standard medication for melasma management | ||||||
| Niosomes | Kojic acid and hydroquinone | NA | <10 µm | NA | • Prolonged drug release pattern | Divanbeygikermani et al. (2018) |
| Arbutin | 0.5% | 114.76 nm | %EE: 35.55% ± 1.59% | • High encapsulation efficiency of arbutin within niosomes | Radmard et al. (2021) | |
| • Enhanced in vivo skin permeation and topical delivery along with reduced transdermal delivery in comparison to arbutin plain gel | ||||||
| • No potential toxicity and high cell viability percentage of about 86% | ||||||
| • No skin irritation potentail | ||||||
| Nanoemulsions | Arbutin and coumaric acid | NA | Pore diameter of 1–50 µm | NA | • Zero-order drug release pattern | Huang et al. (2019) |
| Azelaic acid | 1% | 419 nm | %EE: 84.65% | • Enhanced skin penetration | Jacobus Berlitz et al. (2019) | |
| • Decreased tyrosinase activity | ||||||
| • Improve skin permeation and targeted delivery to dermis and epidermis | ||||||
| • No cytotoxicity potential | ||||||
| • Promising for dermal melasma management | ||||||
| Licorce | 1% | 62.7 nm | NA | • Enhanced whitening effect | Atrux-Tallau et al. (2014a) | |
| • Enhanced epidermal and dermal bioavailability | ||||||
| Enhanced in vitro cellular uptake | ||||||
| Microemulaion | Ascorbic acid | 4% | <100 nm | NA | • Improved skin permeation | Pakpayat et al. (2009) |
| • Enhanced skin protection against UV radiation | ||||||
| • Targeted delivery to the epidermis and dermis layers | ||||||
| • Promising for melasma management and relieve of oxygen matrix damage | ||||||
| Alpha arbutin, lactic acid, and niacinamide | NA | <100 nm | NA | • Enhanced drug stability | Surini and Mellani (2017a) | |
| • Concurrent administration of three active ingredients with various mechanism of actions for melasma management | ||||||
| Hydroquinone | 4% | 358 nm | NA | • Reduced skin irritation or epidermal layer disturbance | Üstündağ Okur et al. (2019) | |
| • Enhanced skin permeation through the stratum corneum | ||||||
| • Enhanced in vitro drug release | ||||||
| • Enhanced photostability of the loaded drug | ||||||
| Kojic acid and arbutin | 0.25% kojic acid & 0.25% arbutin | 25–30 nm | NA | • Enhanced photostability of the loaded drugs | Gallarate et al. (2004) | |
| • The presence of linalool in the prepared formulation could enhance kojic acid photostability | ||||||
| Gold nanoparticles | Arbutin | 0.5% | 10.30–17.13 nm | NA | • Enhanced anti-inflammatory properties | Park et al., 2019b |
| • Improved bioavailability | ||||||
| • Significantly reduced intracellular and extracellular melanin content | ||||||
| • Increases tyrosinase enzyme inhibition | ||||||
| • Reduced arbutin-related toxicities | ||||||
| Polymeric nanoparticles | Kojic acid | 10 µM | 441 nm | %EE: 3.6% | Wang et al. (2012b) | |
| Azelaic acid | 10% | 38.3–117.7 nm | NA | • Significant reduction in melanin synthesis | Tomić et al. (2019a) | |
| • Improved skin diffusivity | ||||||
| • Improved skin bioavailability | ||||||
| • Enhanced water solubility and dissolution rate | ||||||
| Ascorbic acid | 50 mg | 209–260 nm | %EE: 69%–96% | • Sustained drug release within 8 h | Duarah et al. (2017a) | |
| • Enhanced ex vivo skin permeation | ||||||
| Nanocrystals | Azelaic acid | 10% | 38.3–117.7 nm | NA | • Improved skin diffusivity | Tomić et al. (2019a) |
| • Improved skin bioavailability | ||||||
| • Enhanced water solubility and dissolution rate | ||||||
| Transfersomes | Ascorbic palmitate | ∼13% | 110 nm | %EE: 91.3% | • Enhanced drug penetration and deposition within the epidermis layer | Wen et al. (2006b), Li et al. (2021) |
| %LC: 11.9% | • Sustained drug release | |||||
| • Reduced skin irritation | ||||||
| Linoleic acid | 0.05% and 0.1% | 151.2 nm and 237.2 nm | %EE: 23.55 ± 5.29 and 62.64 ± 5.49 | • Enhanced stability of the loaded linoleic acid | Celia et al. (2012) | |
| • Increased penetration through the stratum corneum layer | ||||||
| Fullerenes | L-ascorbic acid and arbutin | 50 µM | NA | NA | • Diminished UVA-induced melanogenesis | Xiao et al. (2007a), Xiao et al. (2007b) |
| • Reduced melanin synthesis |
a
Solid lipid nanoparticles.
b
Nanostructured lipid carriers.
c
Data not available.