Percutaneous absorption and antibacterial activities of lipid nanocarriers loaded with dual drugs for acne treatment.

The aim of this study was to develop lipid nanocarriers that combine tretinoin and tetracycline for the efficient topical delivery to treat acne vulgaris. Two different nanocarriers, nanoemulsions (NEs) and nanostructured lipid carriers (NLCs), were prepared, and we examined their average size, zeta potential, drug encapsulation percentage, and drug permeation via the skin. The antibacterial activities of the nanosystems against Staphylococcus aureus, Pseudomonas aeruginosa, and Propionibacterium acnes were evaluated by an agar diffusion assay and the amount of total protein. A ca. 200-nm particle size was achieved with the prepared nanoparticles. The size increased when incorporating a cationic surfactant. Dual-drug loading did not largely affect the size of negatively charged nanoparticles, but significantly reduced the particle size of positively charged nanocarriers. NEs and NLCs exhibited high entrapment of tretinoin which ranged 60-100%. Tetracycline mainly resided in the aqueous phase, with ca. 10% of molecules located at the particulate interface. An in vitro skin permeation study showed that NLCs enhanced tetracycline flux by about 2-times over the control solution. Tretinoin permeation was generally unaffected after nanoparticulate encapsulation. There was no significant difference in tretinoin delivery before or after tetracycline incorporation, while tetracycline permeation significantly decreased by 2-fold in the dual-drug system. Nanoparticulate loading mostly maintained the antibacterial activity of tetracycline. Negatively charged NEs and NLCs even strengthened the antibacterial ability against S. aureus compared to the control solution. This is the first report examining skin permeation and antibacterial activities of dual-drug nanocarriers for acne treatment.

Evaluation of drug and sunscreen permeation via skin irradiated with UVA and UVB: comparisons of normal skin and chronologically aged skin.

BACKGROUND: Ultraviolet (UV) exposure is the predominant cause of skin aging. A systematic evaluation of drug skin permeation via photoaged skin is lacking. OBJECTIVES: The aim of this work was to investigate whether UVA and UVB affect absorption by the skin of drugs and sunscreens, including tetracycline, quercetin, and oxybenzone. METHODS: The dorsal skin of nude mice was subjected to UVA (24 and 39 J/cm(2)) or UVB (150, 200, and 250 mJ/cm(2)) irradiation. Levels of skin water loss, erythema, and sebum were evaluated, and histological examinations of COX-2 and claudin-1 expressions were carried out. Permeation of the permeants into and through the skin was determined in vitro using a Franz cell. In vivo skin uptake was also evaluated. Senescent skin (24 weeks old) was used for comparison. RESULTS: Wrinkling and scaling were significant signs of skin treated with UVA and UVB, respectively. The level of claudin-1, an indicator of tight junctions (TJs), was reduced by UVA and UVB irradiation. UVA enhanced tetracycline and quercetin skin deposition by 11- and 2-fold, respectively. A similar enhancement was shown for flux profiles. Surprisingly, a lower UVA dose revealed greater enhancement compared to the higher dose. The skin deposition and flux of tetracycline both decreased with UVB exposure. UVB also significantly reduced quercetin flux. The skin absorption behavior of chronologically aged skin approximated that of the UVA group, with photoaged skin showing higher enhancement. UV generally exhibited a negligible effect on modulating oxybenzone permeation. CONCLUSIONS: Skin disruption produced by UV does not necessarily result in enhanced skin absorption. It depends on the UV wavelength, irradiated energy, and physicochemical properties of the permeant. To the best of our knowledge, this is the first report establishing drug permeation profiles for UV-irradiated skin.