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

Shereen A Yousef; Yousuf H Mohammed; Sarika Namjoshi; Jeffrey E Grice; Heather A E Benson; Wedad Sakran; Michael S Roberts

doi:10.3390/pharmaceutics11120639

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

Pharmaceutics. 2019 Dec 1;11(12):639. doi: 10.3390/pharmaceutics11120639.

Authors

Shereen A Yousef^{1

2}, Yousuf H Mohammed¹, Sarika Namjoshi¹, Jeffrey E Grice¹, Heather A E Benson³, Wedad Sakran², Michael S Roberts^{1

4

5}

Affiliations

¹ Therapeutics Research Centre, University of Queensland Diamantina Institute, University of Queensland, 4102 Woolloongabba, QLD, Australia.
² Faculty of Pharmacy, Helwan University, 11795 Helwan, Egypt.
³ School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, 6845 Perth, Australia.
⁴ School of Pharmacy and Medical Sciences, University of South Australia, 5000 Adelaide, Australia.
⁵ Therapeutics Research Centre, Basil Hetzel Institute for Translational Medical Research, The Queen Elizabeth Hospital, 5011 Adelaide, Australia.

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 (J_max) 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.

Keywords: Quality by Design principles; curcumin; cutaneous drug delivery; nanoemulsions; permeation enhancers; skin permeation.