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.

Alopecia areata is managed with oral corticosteroids, which has known side effects for patients. Given that a topical application of formulations containing a corticoid and a substance controlling hair loss progression could reduce or eliminate such adverse effects and increase the patient’s adherence to the treatment, this study prepares polymeric and lipidic nanoparticles (PNPs and NLCs) to co-entrap minoxidil and betamethasone and compares the follicular drug delivery provided by topical application of these nanoparticles. The prepared PNPs loaded 99.1 ± 13.0% minoxidil and 70.2 ± 12.8% betamethasone, while the NLCs entrapped 99.4 ± 0.1 minoxidil and 80.7 ± 0.1% betamethasone. PNPs and NLCs presented diameters in the same range, varying from 414 ± 10 nm to 567 ± 30 nm. The thermal analysis revealed that the production conditions favor the solubilization of the drugs in the nanoparticles, preserving their stability. In in vitro permeation studies with porcine skin, PNPs provided a 2.6-fold increase in minoxidil penetration into the follicular casts compared to the control and no remarkable difference in terms of betamethasone; in contrast, NLCs provided a significant (specifically, a tenfold) increase in minoxidil penetration into the hair follicles compared to the control, and they delivered higher concentrations of betamethasone in hair follicles than both PNPs and the control. Neither PNPs nor NLCs promoted transdermal permeation of the drugs to the receptor solution, which should favor a topical therapy. Furthermore, both nanoparticles targeted approximately 50% of minoxidil delivery to the follicular casts and NLCs targeted 74% of betamethasone delivery to the hair follicles. In conclusion, PNPs and NLCs are promising drug delivery systems for enhancing follicular targeting of drugs, but NLCs showed superior performance for lipophilic drugs.

Alpha-phellandrene (α-PHE), a cyclic monoterpene abundant in volatile oils, has anti-inflammatory and healing properties. A cutaneous formulation using this bioactive could provide benefits in wound healing. However, a simple method that quantifies α-PHE in the skin is still required. Thus, the study aims to develop and validate a high-performance liquid chromatographic (HPLC-UV) method to quantify α-PHE extracted from the skin. The method uses a reversed-phase C18 column (15 cm × 4.6 mm, 5 μm) and a mobile phase consisting of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B) flowing at 0.5 mL/min. The phase concentration (A/B %) along the 40-min run time varied as described: 15/85 (0.01-10 min), 0/100 (10.1-20 min), and 15/85 (20.1-40 min). α-PHE was detected at 263 nm. The method was selective against skin and formulation interferents, linear (r = 0.9995) in a concentration range of 0.5-15.0 μg/mL, precise with an overall variation coefficient lower than 5.5%, accurately achieving recovery from the skin within 92-102%, and sensitive for the proposed application (detection limit = 0.05 µg/mL, quantification limit = 0.14 μg/mL). Finally, the validated method was tested in a skin penetration study, attesting to its success in developing topical formulations containing α-PHE.