Follicle-Targeted Delivery of Betamethasone and Minoxidil Co-Entrapped in Polymeric and Lipid Nanoparticles for Topical Alopecia Areata Treatment.

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.

Chromatographic method for dacarbazine quantification in skin permeation experiments.

Dacarbazine (DTIC) is a chemotherapeutic drug currently used for the systemic treatment of melanomas. Considering the easy access to these tumors, a topical route of drug administration could provide a more comfortable and less toxic treatment. However, DTIC quantification aiming at the design of topical formulations is challenging, pondering all the interferents present in the drug samples recovered from the skin. Hence, this work intended to validate a selective chromatographic method for DTIC determination in skin permeation studies. A reversed-phase C18 column was used as a stationary phase, and gradient elution of a mobile phase consisting of methanol and pH 6.5 sodium phosphate monohydrate buffer (0.01 mol/L) at a flow rate of 1.0 mL/min was implemented. DTIC was detected at 364 nm. The method was selective against skin interferents, linear (r = 0.9995) in a concentration range of 1.0-15.0 µg/mL, precise with an overall variation coefficient lower than 3.8%, accurate achieving recovery from the skin layers within 91-112%, and sensitive for the proposed application (detection limit = 0.10 µg/ mL, quantification limit = 0.30 µg/mL). Furthermore, the analytical method was successfully tested in in vitro skin permeation studies. In conclusion, the developed method is appropriate for DTIC analysis from the skin sample matrix.

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.