Mechanistic Evaluation of Enhanced Curcumin Delivery through Human Skin In Vitro from Optimised Nanoemulsion Formulations Fabricated with Different Penetration Enhancers

Abstract

Curcumin is a natural product with chemopreventive and other properties that are potentially useful in treating skin diseases, including psoriasis and melanoma. However, because of the excellent barrier function of the stratum corneum and the relatively high lipophilicity of curcumin (log P 3.6), skin delivery of curcumin is challenging. We used the principles of a Quality by Design (QbD) approach to develop nanoemulsion formulations containing biocompatible components, including Labrasol and Lecithin as surfactants and Transcutol and ethanol as cosurfactants, to enhance the skin delivery of curcumin. The nanoemulsions were characterised by cryo-SEM, Zeta potential, droplet size, pH, electrical conductivity (EC) and viscosity (η). Physicochemical long-term stability (6 months) was also investigated. The mean droplet sizes as determined by dynamic light scattering (DLS) were in the lower submicron range (20–50 nm) and the average Zeta potential values were low (range: −0.12 to −2.98 mV). Newtonian flow was suggested for the nanoemulsions investigated, with dynamic viscosity of the nanoemulsion formulations ranging from 5.8 to 31 cP. The droplet size of curcumin loaded formulations remained largely constant over a 6-month storage period. The inclusion of terpenes to further enhance skin permeation was also examined. All nanoemulsions significantly enhanced the permeation of curcumin through heat-separated human epidermal membranes, with the greatest effect being a 28-fold increase in maximum flux (Jmax) achieved with a limonene-based nanoemulsion, compared to a 60% ethanol in water control vehicle. The increases in curcumin flux were associated with increased skin diffusivity. In summary, we demonstrated the effectiveness of nanoemulsions for the skin delivery of the lipophilic active compound curcumin, and elucidated the mechanism of permeation enhancement. These formulations show promise as delivery vehicles for curcumin to target psoriasis and skin cancer, and more broadly for other skin delivery applications.

Nanoemulsion Stabilized by Safe Surfactin from Bacillus subtilis as a Multifunctional, Custom-Designed Smart Delivery System

“…However, one can see that thanks to coumarin encapsulation in the nanoemulsion, the latter penetrates the skin (examined 1 h after application), stopping at the dermis border ( Figure 5 C,D). Similar results were obtained by Sarheed et al [ 59 ], Yousef et al [ 36 ] and Nastiti et al [ 60 ], whereby the encapsulation of loratadine, curcumin and resveratrol, respectively, in a nanoemulsion enhanced the permeability of these compounds through the skin.…”

“…Additionally, aggregation of molecules was observed in the nanoemulsions. Smaller particle sizes ranging from 20 to 50 nm were obtained by Yousef et al for a nanoemulsion with curcumin [ 36 ]. In their study they used other surfactants, which suggests that the choice of surfactant may influence the size of the particles.…”

Novel Nanocarriers for Targeted Topical Skin Delivery of the Antioxidant Resveratrol

“…The HLB (hydrophilic-lipophilic balance) of this surfactant is between 14-16 [33] and thus appropriate for o/w nanoemulsions. Transcutol ® P, a high purity grade of diethylene glycol monoethyl ether (DEGEE), was selected as the cosurfactant because it is an excellent and safe hydroalcoholic solubilizer and skin permeation enhancer without compromising skin integrity [28,[35][36][37][38]. PBS pH 6 was used as the aqueous phase to maintain the stability of RSV [12] and to support skin compatibility [25].…”

Evaluating the effect of rice (Oryza sativa L.: SRNC05053-6-2) crude extract on psoriasis using in vitro and in vivo models

“…Several natural products, such as curcumin 11 , 12 , cannabinoid 13 , anthocyanin (and its derivatives), were developed for the alleviation of psoriasis 14 – 19 . These products exert the desired effects on psoriasis via different mechanisms.…”