Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 172, Issue -, Pages 78-88Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2022.02.003
Keywords
Minoxidil; Latanoprost; Nanoparticle; Alopecia; Hair follicle; Skin
Categories
Funding
- CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [303066/2018-0]
- University of Brasilia [DPI/DPG 02/2021]
- CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
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This study aimed to develop a safe formulation based on nanostructured lipid carriers (NLC) that can deliver minoxidil and latanoprost to the hair follicles. The results showed that the NLC effectively encapsulated the drugs, penetrated into the hair follicles, and demonstrated good tolerance.
Alopecia is a condition associated with different etiologies, ranging from hormonal changes to chemotherapy, that affects over 80 million people in the USA. Nevertheless, there are currently few FDA-approved drugs for topical treatment, and existing formulations still present skin irritation issues, compromising treatment adher-ence. This work aimed to develop a safe formulation based on nanostructured lipid carriers (NLC) that entrap an association of minoxidil and latanoprost and target drug delivery to the hair follicles. To do so, thermal tech-niques combined with FTIR were used to assess the chemical compatibility of the proposed drug association. Then, NLC with 393.5 +/- 36.0 nm (PdI < 0.4) and +22.5 +/- 0.2 mV zeta potential were produced and shown to entrap 86.9% of minoxidil and 99.9% of latanoprost efficiently. In vitro, the free drug combination was indicated to exert positive effects over human primary epidermal keratinocytes, supporting cell proliferation, migration and inducing the mRNA expression of MKI67 proliferation marker and VEGF - a possible effector for minoxidil-mediated hair growth. Interestingly, such a favorable drug combination profile was optimized when delivered using our NLC. Furthermore, according to the HET-CAM and reconstructed human epidermis assays, the nanoformulation was well tolerated. Finally, drug penetration was evaluated in vitro using porcine skin. Such experiments indicated that the NLC could be deposited preferentially into the hair follicles, causing a consid-erable increase in the penetration of the two drugs in such structures, compared to the control (composed of the free compounds) and generating a target-effect of approximately 50% for both drugs. In summary, present results suggest that hair follicle-targeted delivery of the minoxidil and latanoprost combination is a promising alter-native to treat alopecia.
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