The influence of sebaceous content on the performance of nanosystems designed for the treatment of follicular diseases

Nanostructures have been proposed as drug delivery systems in the treatment of hair follicle-related conditions because of their well-reported tendency to accumulate into the hair follicle shafts extending drug release. However, little is known about colloids behavior under diseased conditions as acne vulgaris, folliculitis, hidradenitis suppurativa, or capillary keratosis, in which there is an excess of sebum secretion that clogs the hair follicles. Here, we evaluated the influence of the sebaceous content on the performance of nanosystems by using an in vitro sebaceous skin model, in which the skin was massaged with a mixture of mutton tallow and vegetable oil in a 1:1 (w/w) preceding the permeation experiments. A nanostructured lipid carrier containing clindamycin phosphate (~90% of encapsulation efficiency) was used as a formulation model. Nanoparticles presented a mean diameter of 391.9 ± 8.6 nm, PDI of 0.16 ± 0.05, and positive zeta potential (+18.5 ± 1.5 mV). Stability studies confirmed nanoparticles were stable throughout all experiments, and drug release studies confirmed the controlled release profile. The results indicated the nanosystem performance was superior to the free drug in targeting the hair follicle in conventional skin permeation experiments, but no advantages of the colloidal system were observed when using the sebaceous skin model. Hence, the sebaceous content hampered nanoparticles deposition into the hair follicle shafts. In conclusion, the physiological skin condition must be considered when designing targeted drug delivery systems. The novel sebaceous skin model proposed in this paper can be used to evaluate, in a more realistic condition, the performance of the nanostructured systems intended for topical drug delivery in conditions of excess sebaceous secretion. [Display omitted]