A novel chitosan nanocapsule for enhanced skin penetration of cyclosporin A and effective hair growth in vivo
- 40 Downloads
Hair loss due to medical conditions, such as alopecia, male pattern baldness, and cancer chemotherapy treatment, has been a common problem for many individuals. Cyclosporin A (CsA), a fungal metabolite, has been reported to be a hair growth modulatory agent and is a potential drug for hair regeneration. However, the effect of topical application of CsA is limited by its poor water solubility. Several delivery systems developed to enhance its solubility still showed poor skin penetration. To overcome these limitations, in this study, we have developed a novel chitosan nanocapsule platform using Pluronic F127 and chitosan without any chemical crosslinking or complicated preparation steps for the enhanced water solubility and high transdermal penetration of CsA. The chitosan nanocapsules (ChiNCs) optimized in terms of structural stability by using chitosan with various molecular weights ranging from 3 to 100 kDa enhanced the skin permeation of CsA through human cadaver skin in vitro. Topical administration of the CsA loaded ChiNCs increased the hair follicles by c.a. 7 times higher than that of the control group, and effectively induced hair growth in C57BL/6 mice in vivo. These results suggest that ChiNCs could be used as a platform for effective transdermal delivery of various hydrophobic drugs.
Keywordschitosan nanocapsule cyclosporin A transdermal delivery hair growth
Unable to display preview. Download preview PDF.
This research was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (Nos. NRF-2018R1D1A1B07043620 and 2018R1A4A1024963) and the grant of Korea Institute of Ceramic Engineering and Technology (KICET).
- N’Guessan, B. B.; Sanchez, H.; Zoll, J.; Ribera, F.; Dufour, S.; Lampert, E.; Kindo, M.; Geny, B.; Ventura-Clapier, R.; Mettauer B. Oxidative capacities of cardiac and skeletal muscles of heart transplant recipients: Mitochondrial effects of cyclosporin-A and its vehicle Cremophor-EL. Fundam. Clin. Pharmacol. 2014, 28, 151–160.CrossRefGoogle Scholar
- Maurer, M.; Handjiski, B.; Paus, R. Hair growth modulation by topical immunophilin ligands: Induction of anagen, inhibition of massive catagen development, and relative protection from chemotherapy-induced alopecia. Am. J. Pathol. 1997, 150, 1433–1441.Google Scholar
- Paus, R.; Stenn, K. S.; Link, R. E. The induction of anagen hair growth in telogen mouse skin by cyclosporine A administration. Lab. Invest. 1989, 60, 365–369.Google Scholar
- Paus, R.; Handjiski, B.; Eichmuller, S.; Czarnetzki, B. M. Chemotherapy-induced alopecia in mice. Induction by cyclophosphamide, inhibition by cyclosporine A, and modulation by dexamethasone. Am. J. Pathol. 1994, 144, 719–734.Google Scholar
- Sawada, M.; Terada, N.; Taniguchi, H.; Tateishi, R.; Mori, Y. Cyclosporin A stimulates hair growth in nude mice. Lab. Invest. 1987, 56, 684–686.Google Scholar
- Xu, W. R.; Fan, W. X.; Yao, K. Cyclosporine A stimulated hair growth from mouse vibrissae follicles in an organ culture model. J. Biomed. Mater. Res. 2012, 26, 372–380.Google Scholar
- Lan, S. W.; Liu, F. L.; Zhao, G. F.; Zhou, T.; Wu, C. L.; Kou, J. N.; Fan, R. R.; Qi, X. J.; Li, Y. H.; Jiang, Y. X. et al. Cyclosporine A increases hair follicle growth by suppressing apoptosis-inducing factor nuclear translocation: A new mechanism. Fundam. Clin. Pharmacol. 2015, 29, 191–203.CrossRefGoogle Scholar
- Wu, J.; Zhao, L. L.; Xu, X. D.; Bertrand, N. C.; Choi, W. I.; Yameen, B. S.; Shi, J. J.; Shah, V.; Mulvale, M.; MacLean, J. L. et al. Hydrophobic cysteine poly(disulfide)-based redox-hypersensitive nanoparticle platform for cancer theranostics. Angew. Chem., Int. Ed. 2015, 54, 9218–9223.CrossRefGoogle Scholar
- Alishahi, A.; Mirvaghefi, A.; Tehrani, M. R.; Farahmand, H.; Koshio, S.; Dorkoosh, F. A.; Elsabee, M. Z. Chitosan nanoparticle to carry vitamin C through the gastrointestinal tract and induce the non-specific immunity system of rainbow trout (Oncorhynchus mykiss). Carbohydr. Polym. 2011, 86, 142–146.CrossRefGoogle Scholar
- Zhuo, Y.; Han, J.; Tang, L.; Liao, N.; Gui, G. F.; Chai, Y. Q.; Yuan, R. Quenching of the emission of peroxydisulfate system by ferrocene functionalized chitosan nanoparticles: A sensitive “signal off” electro-chemiluminescence immunosensor. Sens. Actuators, B: Chem. 2014, 192, 791–795.CrossRefGoogle Scholar
- Tiyaboonchai, W. Chitosan nanoparticles: A promising system for drug delivery. Naresuan Univ. J. 2003, 11, 51–66.Google Scholar
- Niwa, T.; Takeuchi, H.; Hino, T.; Kunou, N.; Kawashima, Y. Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D, L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior. J. Control. Release 1993, 25, 89–98.CrossRefGoogle Scholar
- Lin, W. H.; Xiang, L. J.; Shi, H. X.; Zhang, J.; Jiang, L. P.; Cai, P. T.; Lin, Z. L.; Lin, B. B.; Huang, Y.; Zhang, H. L. et al. Fibroblast growth factors stimulate hair growth through β-catenin and Shh expression in C57BL/6 mice. BioMed Res. Int. 2015, 2015, 730139.Google Scholar