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Latanoprost Loaded in Polymeric Nanocapsules for Effective Topical Treatment of Alopecia

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Abstract

Latanoprost has recently been used to treat alopecia as it causes an increase in the capillary density of patients. This work presents for the first time the development of polymeric nanocapsules containing latanoprost for the topical treatment of alopecia. Poly-ε-caprolactone nanocapsules loading latanoprost were developed by nanoprecipitation of the polymer on the surface of drug oily nanodroplets. The method encapsulated 93.9 ± 0.4% of the drug into nanocapsules of 197.8 (± 1.2) nm (PdI = 0.15 ± 0.01). The nanosystem presented a zeta potential equal to − 30.1 ± 1.8 mV and was stable for at least 90 days when stored at 6°C. The colloidal aqueous dispersion was non-irritating, according to the in vitro HET-CAM test. The nanocapsules improved latanoprost accumulation into the hair follicles when topically applied on porcine skin, delivering 30% more drug to these skin structures relative to the control solution (P < 0.05). Also, with a simple manual massage, latanoprost accumulation was increased by twofold (P < 0.05). In conclusion, in addition to being a stable and safe formulation, nanocapsules enhanced latanoprost accumulation into the hair follicles, being a nanosystem with high potential for use as a topical formulation for the treatment of androgenic alopecia.

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References

  1. Adil A, Godwin M. The effectiveness of treatments for androgenetic alopecia: a systematic review and meta-analysis. J Am Acad Dermatol. 2017;77:136–41. https://doi.org/10.1016/j.jaad.2017.02.054.

    Article  PubMed  Google Scholar 

  2. Messenger AG, Rundegren J. Minoxidil: mechanisms of action on hair growth. Br J Dermatol. 2004;150:186–94. https://doi.org/10.1111/j.1365-2133.2004.05785.x.

    Article  CAS  PubMed  Google Scholar 

  3. Pereira MN, Schulte HL, Duarte N, Lima EM, Sá-Barreto LL, Gratieri T, et al. Solid effervescent formulations as new approach for topical minoxidil delivery. Eur J Pharm Sci. 2017;96:411–9. https://doi.org/10.1016/j.ejps.2016.10.016.

    Article  CAS  PubMed  Google Scholar 

  4. Matos BN, Reis TA, Gratieri T, Gelfuso GM. Chitosan nanoparticles for targeting and sustaining minoxidil sulphate delivery to hair follicles. Int J Biol Macromol. 2015;75:225–9. https://doi.org/10.1016/j.ijbiomac.2015.01.036.

    Article  CAS  PubMed  Google Scholar 

  5. Nagai N, Iwai Y, Sakamoto A, Otake H, Oaku Y, Abe A, et al. Drug delivery system based on minoxidil nanoparticles promotes hair growth in C57BL/6 mice. Int J Nanomedicine. 2019;14:7921–31. https://doi.org/10.2147/IJN.S225496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Takeuchi I, Hida Y, Makino K. Minoxidil-encapsulated poly(L-lactide-co-glycolide) nanoparticles with hair follicle delivery properties prepared using W/O/W solvent evaporation and sonication. Biomed Mater Eng. 2018;29(2):217–28. https://doi.org/10.3233/BME-171724.

    Article  CAS  PubMed  Google Scholar 

  7. Jain B, Singh B, Katare OP, Vyas SP. Development and characterization of minoxidil-loaded liposomal system for delivery to pilosebaceous units. J Liposome Res. 2010;20:105–14. https://doi.org/10.1080/08982100903161449.

    Article  CAS  PubMed  Google Scholar 

  8. Meymandi SS, et al. Comparison of the efficacy of niosomal minoxidil with conventional minoxidil in the treatment of androgenetic alopecia: a randomized, controlled, double-blind clinical trial. J Dermatol Cosmet. 2014;5(2):53–60.

    Google Scholar 

  9. Mura S, Manconi M, Fadda AM, Sala MC, Perricci J, Pini E, et al. Penetration enhancer-containing vesicles (PEVs) as carriers for cutaneous delivery of minoxidil: in vitro evaluation of drug permeation by infrared spectroscopy. Pharm Dev Technol. 2013;18:1339–45. https://doi.org/10.3109/10837450.2012.685661.

    Article  CAS  PubMed  Google Scholar 

  10. Aljuffali IA, Sung CT, Shen FM, Huang CT, Fang JY. Squarticles as a lipid nanocarrier for delivering diphencyprone and minoxidil to hair follicles and human dermal papilla cells. AAPS J. 2014;16:140–50. https://doi.org/10.1208/s12248-013-9550-y.

    Article  CAS  PubMed  Google Scholar 

  11. Gomes MJ, et al. Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies. Int J Nanomedicine. 2014;9:1231–42. https://doi.org/10.2147/IJN.S45561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Padois K, Cantiéni C, Bertholle V, Bardel C, Pirot F, Falson F. Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil. Int J Pharm. 2011;416:300–4. https://doi.org/10.1016/j.ijpharm.2011.06.014.

    Article  CAS  PubMed  Google Scholar 

  13. Wang W, Chen L, Huang X, Shao A. Preparation and characterization of minoxidil loaded nanostructured lipid carriers. AAPS PharmSciTech. 2016;18:509–16. https://doi.org/10.1208/s12249-016-0519-x.

    Article  CAS  PubMed  Google Scholar 

  14. Goren A, Shapiro J, Roberts J, McCoy J, Desai N, Zarrab Z, et al. Clinical utility and validity of minoxidil response testing in androgenetic alopecia. Dermatol Ther. 2015;28(1):13–6. https://doi.org/10.1111/dth.12164.

    Article  PubMed  Google Scholar 

  15. Choi YM, Diehl J, Levins PC. Promising alternative clinical uses of prostaglandin F2α analogs: beyond the eyelashes. J Am Acad Dermatol. 2015;72:712–6. https://doi.org/10.1016/j.jaad.2014.10.012.

    Article  CAS  PubMed  Google Scholar 

  16. Ocampo-Garza J, Griggs J, Tosti A. New drugs under investigation for the treatment of alopecias. Expert Opin Investig Drugs. 2019;28:275–84. https://doi.org/10.1080/13543784.2019.1568989.

    Article  CAS  PubMed  Google Scholar 

  17. Bloch LD, et al. Latanoprost and minoxidil: comparative double-blind, placebo-controlled study for the treatment of hair loss. Surg Cosmet Dermatol. 2018;10:39–43. https://doi.org/10.5935/scd1984-8773.20181011015.

    Article  Google Scholar 

  18. Blume-Peytavi U, Lönnfors S, Hillmann K, Garcia Bartels N. A randomized double-blind placebo-controlled pilot study to assess the efficacy of a 24-week topical treatment by latanoprost 0.1% on hair growth and pigmentation in healthy volunteers with androgenetic alopecia. J Am Acad Dermatol. 2012;66:794–800. https://doi.org/10.1016/j.jaad.2011.05.026.

    Article  CAS  PubMed  Google Scholar 

  19. Coronel-Pérez IM, Rodríguez-Rey EM, Camacho-Martínez FM. Latanoprost in the treatment of eyelash alopecia in alopecia areata universalis. J Eur Acad Dermatol Venereol. 2010;24:481–5. https://doi.org/10.1111/j.1468-3083.2009.03543.x.

    Article  CAS  PubMed  Google Scholar 

  20. Miladi K, Sfar S, Fessi H, Elaissari A. Nanoprecipitation process: from particle preparation to in vivo applications. In: Vauthier C, Ponchel G, editors. Polymer nanoparticles for nanomedicines. Switzerland: Springer International Publishing; 2016. p. 17–53.

    Chapter  Google Scholar 

  21. Oliveira PM, Sampaio TR, França LCF, Gratieri T, Cunha-Filho M, Gelfuso GM. LC-MS bioanalytical method for simultaneous determination of latanoprost and minoxidil in the skin. J Pharm Biom Anal. 2020;113373:113373. https://doi.org/10.1016/j.jpba.2020.113373.

    Article  CAS  Google Scholar 

  22. Vinardell MP, Macian M. Comparative-study of the HET-CAM test and the Draize eye test for assessment of irritancy potential. Toxicol in Vitro. 1995;8:467–70.

    Article  Google Scholar 

  23. Angelo T, el-Sayed N, Jurisic M, Koenneke A, Gelfuso GM, Cunha-Filho M, et al. Effect of physical stimuli on hair follicle deposition of clobetasol-loaded lipid nanocarriers. Sci Rep. 2020;10:176. https://doi.org/10.1038/s41598-019-56760-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ushirobira CY, Afiune LAF, Pereira MN, Cunha-Filho M, Gelfuso GM, Gratieri T. Dutasteride nanocapsules for hair follicle targeting: effect of chitosan-coating and physical stimulus. Int J Biol Macromol. 2020;151:56–61. https://doi.org/10.1016/j.ijbiomac.2020.02.143.

    Article  CAS  PubMed  Google Scholar 

  25. Patzelt A, Richter H, Knorr F, Schäfer U, Lehr CM, Dähne L, et al. Selective follicular targeting by modification of the particle sizes. J Control Release. 2011;150:45–8. https://doi.org/10.1016/J.Jconrel.2010.11.015.

    Article  CAS  PubMed  Google Scholar 

  26. Radtke M, Patzelt A, Knorr F, Lademann J, Netz RR. Ratchet effect for nanoparticle transport in hair follicles. Eur J Pharm Biopharm. 2017;116:125–30. https://doi.org/10.1016/j.ejpb.2016.10.005.

    Article  CAS  PubMed  Google Scholar 

  27. Malikmammadov E, Tanir TE, Kiziltay A, Hasirci V, Hasirci N. PCL and PCL-based materials in biomedical applications. J Biomater Sci Polym Ed. 2018;29(7–9):863–93. https://doi.org/10.1080/09205063.2017.1394711.

    Article  CAS  PubMed  Google Scholar 

  28. Contri RV, Fiel LA, Alnasif N, Pohlmann AR, Guterres SS, Schäfer-Korting M. Skin penetration and dermal tolerability of acrylic nanocapsules: influence of the surface charge and a chitosan gel used as vehicle. Int J Pharm. 2016;507(1–2):12–20. https://doi.org/10.1016/j.ijpharm.2016.03.046.

    Article  CAS  PubMed  Google Scholar 

  29. Quintão WSC, et al. Microemulsions incorporating Brosimum gaudichaudii extracts as a topical treatment for vitiligo: in vitro stimulation of melanocyte migration and pigmentation. J Mol Liq. 2019;294:111685. https://doi.org/10.1016/j.molliq.2019.111685.

    Article  CAS  Google Scholar 

  30. Ferreira-Nunes R, Silva SMM, Souza PEN, Magalhães PO, Cunha-Filho M, Gratieri T, et al. Incorporation of Eugenia dysenterica extract in microemulsions preserves stability, antioxidant effect and provides enhanced cutaneous permeation. J Mol Liq. 2018;265:408–15. https://doi.org/10.1016/j.molliq.2018.06.023.

    Article  CAS  Google Scholar 

  31. Napolitano M, Cantelli M, Vastarella M, Nappa P, Fabbrocini G, Patruno C. Allergic contact dermatitis probably caused by latanoprost during treatment for alopecia areata. Contact Dermatitis. 2019;81:67–8. https://doi.org/10.1111/cod.13228.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would also like to thank “Sabugy Agroindustria e Comercio de Alimentos LTDA” for gently providing the porcine ears, as well as Ricardo Ferreira Nunes for his important technical assistance.

Funding

The authors acknowledge the Brazilian funding agency CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and University of Brasília (Editals DPI/UnB 04/2019 and 03/2020) for financial support, and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for providing the grants for ACS Oliveira and PM Oliveira.

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Authors and Affiliations

  1. Laboratory of Food, Drugs, and Cosmetics (LTMAC), School of Health Sciences, University of Brasília, Brasilia, DF, 70910-900, Brazil

    Ana Christina S. Oliveira, Paula M. Oliveira, Marcilio Cunha-Filho, Tais Gratieri & Guilherme M. Gelfuso

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  1. Ana Christina S. Oliveira
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  2. Paula M. Oliveira
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  3. Marcilio Cunha-Filho
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  4. Tais Gratieri
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  5. Guilherme M. Gelfuso
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Correspondence to Guilherme M. Gelfuso.

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Oliveira, A.C.S., Oliveira, P.M., Cunha-Filho, M. et al. Latanoprost Loaded in Polymeric Nanocapsules for Effective Topical Treatment of Alopecia. AAPS PharmSciTech 21, 305 (2020). https://doi.org/10.1208/s12249-020-01863-1

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