Curcumin quantification in skin and mucosa: Optimization of extraction and chromatographic method validation.

Curcumin is a natural phenol found in the rhizome of Curcuma longa. It has been studied to treat several human carcinomas, such as melanomas and breast, head and neck, prostate, and ovary cancers. Here, we develop and validate a method for recovering curcumin from the skin layers and mucosa and selectively quantifying it, aiming to support permeation studies in developing topical formulations containing the natural compound. Recovery of curcumin from the stratum corneum, remaining skin, and mucosa was performed using ethanol, DMSO/ethanol, and DMSO, respectively, under mild stirring for specific periods. The separation of curcumin from the other curcuminoids, skin, and mucosa interferents was obtained using a C18 column as a stationary phase. The mobile phase was composed of pH 3.0 phosphoric acid at 1.0 mmol/L and acetonitrile (47:53, v/v), which flowed at 1 mL min-1. UV-Vis detection of curcumin was at 424 nm. The chromatographic method was selective, linear (r > 0.999), with a regression curve in the concentration range from 1.0 to 30.0 µg mL-1, robust, precise, and accurate, with curcumin recovery rates higher than 95 ± 7 % from the mucosa, 82 ± 2 % from the stratum corneum, and 65 ± 10 % from the remaining skin. Finally, the method was successfully used in a skin permeation test performed with porcine skin and mucosa. The validated method is, therefore, suitable for the recovery and quantification of curcumin from the skin layers and mucosa, favoring the development of new topical formulations destined for these sites of administration.

Topical Treatment for Scarring and Non-Scarring Alopecia: An Overview of the Current Evidence.

Alopecia is a clinical condition related to hair loss that can significantly affect both male and female adults' quality of life. Despite the high market demand, only few drugs are currently approved for alopecia treatment. Topical formulations still bring drawbacks, such as scalp irritation with frequent use, and low drug absorption to the site of action, which limits the efficacy. The most recent research points out that different formulation technology could circumvent the aforementioned flaws. Such technology includes incorporation of drugs in rigid or deformable nanoparticles, strategies involving physical, energetical and mechanical techniques, such as iontophoresis, sonophoresis, microneedling, and the use of solid effervescent granules to be hydrated at the moment of application in the scalp. In this paper, the progress of current research on topical formulations dedicated to the treatment of alopecia is reviewed and discussed.

Nanostructured lipid carriers for hair follicle-targeted delivery of clindamycin and rifampicin to hidradenitis suppurativa treatment.

Hidradenitis suppurativa is a chronic and debilitating inflammatory condition related to a permanent obstruction of the pilosebaceous units. Until nowadays, therapeutic options are unsatisfactory. Here, we propose nanostructured lipid carriers (NLC) entrapping an association of clindamycin phosphate (CDM) and rifampicin (RIF) as a topical alternative for the treatment of the disease. Chemical compatibility between the drugs was demonstrated using thermal analysis combined with ATR-FTIR and X-ray powder diffraction assays. Nanocarriers' diameter was narrowly distributed (polydispersity index = 0.2) around 400 ± 14 nm, they possess a negative surface charge (-48.9 ± 0.7 mV) and high drug entrapment efficiencies (80.2 ± 0.4 % and 93.4 ± 0.7 % for CDM and RIF, respectively). The formulation proved to be safe for the topical application, as it was non-irritant on both HET-CAM and reconstructed human epidermis (RHE) assays. Spin-label EPR indicated an NLC affinity for the lipidic domains of stratum corneum, which could benefit the targeting of the sebaceous units. Indeed, when applied on the skin in vitro, even when mimicking the sebaceous condition, NLC accumulated into the hair follicles openings, not altering the amount of accumulated CDM and significantly increasing by 12-fold the uptake of RIF in these structures. In conclusion, developed NLC formulation incorporating the antibiotics CDM and RIF is a promising strategy for the topical treatment of hidradenitis suppurativa or other infections that may affect the pilosebaceous units.

Targeted clindamycin delivery to pilosebaceous units by chitosan or hyaluronic acid nanoparticles for improved topical treatment of acne vulgaris.

We developed chitosan or hyaluronic acid nanoparticles to entrap clindamycin and evaluated for the first time the impact of these two polymeric nanosystems on the targeted drug delivery to the pilosebaceous units, considering the sebaceous characteristics of skin affected by acne. Chitosan and hyaluronic acid nanoparticles respectively presented diameters of 362 ± 19 nm and 417 ± 9 nm (PDI < 0.47), entrapped 42 % and 48 % of the clindamycin content (drug loading of 8.8 % and 0.5 %) and had opposite surface charges (+27.7 ± 0.9 mV and -30.2 ± 2.7 mV). Although only the hyaluronic acid nanoparticles showed increased deposition of the drug into the pilosebaceous structures, both nanoparticles revealed enhanced targeted delivery of clindamycin to these structures as compared to commercial formulation (53 ± 20 % and 77 ± 9% of the total drug that penetrated the skin was found on the pilosebaceous units from, respectively, chitosan and hyaluronic acid nanoparticles). Remarkably, the "targeting potential" of the nanoparticles was more pronounced when the skin was pretreated to simulate a sebaceous condition. In conclusion, both polymeric nanocarriers targeted drug delivery to the pilosebaceous structures at different extensions and, in the case of oily skin conditions, such targeting was increased.