AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Article Link
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

A novel chitosan nanocapsule for enhanced skin penetration of cyclosporin A and effective hair growth in vivo

Jin Sil Lee1,2,§Youngmin Hwang2Hyeryeon Oh1,2,§Sunghyun Kim1Jin-Hwa Kim3Jeung-Hoon Lee3Yong Chul Shin3,4Giyoong Tae2( )Won Il Choi1( )
Center for Convergence Bioceramic MaterialsConvergence R&D DivisionKorea Institute of Ceramic Engineering and Technology202Osongsaengmyeong 1-roOsong-eupHeungdeok-guCheongjuChungbuk202Republic of Korea
School of Materials Science and EngineeringGwangju Institute of Science and Technology123 Cheomdan-gwagiroBuk-guGwangju61005Republic of Korea
SKINMED Co.Ltd.Daejeon34028Republic of Korea
AmicogenInc.64 Dongburo 1259JinsungJinju52621Republic of Korea

§Jin Sil Lee and Youngmin Hwang contributed equally to this work.

Show Author Information

Graphical Abstract

Abstract

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.

Electronic Supplementary Material

Download File(s)
12274_2019_2546_MOESM1_ESM.pdf (1.8 MB)

References

1

Borel, J. F. ; Feurer, C. ; Gubler, H. U. ; Stähelin H. Biological effects of cyclosporin A: A new antilymphocytic agent. Agents Actions. 1994, 43, 179–186.

2

de Arriba, G. ; Calvino, M. ; Benito, S. ; Parra T. Cyclosporine A-induced apoptosis in renal tubular cells is related to oxidative damage and mitochondrial fission. Toxicol. Lett. 2013, 218, 30–38.

3

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.

4

Jiang, H. ; Yamamoto, S. ; Kato, R. Induction of anagen in telogen mouse skin by topical application of FK506, a potent immunosuppressant. J. Invest. Dermatol. 1995, 104, 523–525.

5

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.

6

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.

7

Horsley, V. ; Aliprantis, A. O. ; Polak, L. ; Glimcher, L. H. ; Fuchs, E. NFATc1 balances quiescence and proliferation of skin stem cells. Cell. 2008, 132, 299–310.

8

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.

9

Sawada, M. ; Terada, N. ; Taniguchi, H. ; Tateishi, R. ; Mori, Y. Cyclosporin A stimulates hair growth in nude mice. Lab. Invest. 1987, 56, 684–686.

10

Yamamoto, S. ; Kato, R. Hair growth-stimulating effects of cyclosporin A and FK506, potent immunosuppressants. J. Dermatol. Sci. 1994, 7, S47–S54.

11

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.

12

Ezure, T. ; Suzuki, Y. Involvement of sonic hedgehog in cyclosporine A induced initiation of hair growth. J. Dermatol. Sci. 2007, 47, 168–170.

13

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.

14

González, A. ; Ravassa, S. ; Beaumont, J. ; López, B. ; Díez, J. New targets to treat the structural remodeling of the myocardium. J. Am. Coll. Cardiol. 2011, 58, 1833–1843.

15

Polster, B. M. ; Basañez, G. ; Etxebarria, A. ; Hardwick, J. M. ; Nicholls, D. G. Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J. Biol. Chem. 2005, 280, 6447–6454.

16

Jain, S. ; Mittal, A. ; Jain, A. K. ; Mahajan, R. R. ; Singh, D. Cyclosporin a loaded PLGA nanoparticle: Preparation, optimization, in-vitro characterization and stability studies. Curr. Nanosci. 2010, 6, 422–431.

17

Watanabe, S. ; Mochizuki, A. ; Wagatsuma, K. ; Kobayashi, M. ; Kawa, Y. ; Takahashi, H. Hair growth on nude mice due to cyclosporin A. J. Dermatol. 1991, 18, 714–719.

18

Onoue, S. ; Sato, H. ; Kawabata, Y. ; Mizumoto, T. ; Hashimoto, N. ; Yamada, S. In vitro and in vivo characterization on amorphous solid dispersion of cyclosporine A for inhalation therapy. J. Control. Release2009, 138, 16–23.

19

Al-Meshal, M. A. ; Khidr, S. H. ; Bayomi, M. A. ; Al-Angary, A. A. Oral administration of liposomes containing cyclosporine: A pharmacokinetic study. Int. J. Pharm. 1998, 168, 163–168.

20

Müller, R. H. ; Runge, S. A. ; Ravelli, V. ; Thünemann, A. F. ; Mehnert, W. ; Souto, E. B. Cyclosporine-loaded solid lipid nanoparticles (SLN®): Drug-lipid physicochemical interactions and characterization of drug incorporation. Eur. J. Pharm. Biopharm. 2008, 68, 535–544.

21

Italia, J. L. ; Bhatt, D. K. ; Bhardwaj, V. ; Tikoo, K. ; Ravi Kumar M. N. V. PLGA nanoparticles for oral delivery of cyclosporine: Nephrotoxicity and pharmacokinetic studies in comparison to Sandimmune Neoral®. J. Control. Release2007, 119, 197–206.

22

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.

23

Zheng, Y. H. ; You, X. R. ; Guan, S. Y. ; Huang, J. ; Wang, L. Y. ; Zhang, J. A. ; Wu, J. Poly(Ferulic Acid) with an anticancer effect as a drug nanocarrier for enhanced colon cancer therapy. Adv. Funct. Mater. 2019, 29, 1808646

24

Choi, W. I. ; Lee, J. H. ; Kim, J. Y. ; Kim, J. C. ; Kim, Y. H. ; Tae, G. Efficient skin permeation of soluble proteins via flexible and functional nano-carrier. J. Control. Release2012, 157, 272–278.

25

Sapra, B. ; Jain, S. ; Tiwary, A. K. Effect of Asparagus racemosus extract on transdermal delivery of carvedilol: A mechanistic study. AAPS PharmSciTech. 2009, 10, 199–210.

26

Smith, J. ; Wood, E. ; Dornish, M. Effect of chitosan an epithelial cell tight junctions. Pharm. Res. 2004, 21, 43–49.

27

He, W. ; Guo, X. X. ; Zhang, M. Transdermal permeation enhancement of N-trimethyl chitosan for testosterone. Int. J. Pharm. 2008, 356, 82–87.

28

Biruss, B. ; Valenta, C. Skin permeation of different steroid hormones from polymeric coated liposomal formulation. Eur. J. Pharm. Biopharm. 2006, 62, 210–219.

29

Mohammed, M. A. ; Syeda, J. T. M. ; Wasan, K. M. ; Wasan, E. K. An overview of chitosan nanoparticles and its application in non-parenteral drug delivery. Pharmaceutics2017, 9, 53.

30

Tu, Y. ; Wang, X. ; Lu, Y. ; Zhang, H. ; Yu, Y. ; Chen, Y. ; Liu, J. ; Sun, Z. ; Cui, L. ; Gao, J. et al. Promotion of the transdermal delivery of protein drugs by N-trimethyl chitosan nanoparticles combined with polypropylene electret. Int. J. Nanomedicine2016, 11, 5549–5561.

31

He, W. ; Guo, X. X. ; Xiao, L. H. ; Feng, M. Study on the mechanisms of chitosan and its derivatives used as transdermal penetration enhancers. Int. J. Pharm. 2009, 382, 234–243.

32

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.

33

Hembram, K. C. ; Prabha, S. ; Chandra, R. ; Ahmed, B. ; Nimesh, S. Advances in preparation and characterization of chitosan nanoparticles for therapeutics. Artif. Cells Nanomed. Biotechnol. 2016, 44, 305–314.

34

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.

35

Chen, Y. ; Mohanraj, V. J. ; Wang, F. ; Benson, H. A. E. Designing chitosandextran sulfate nanoparticles using charge ratios. AAPS PharmSciTech2007, 8, 131–139.

36

Tiyaboonchai, W. Chitosan nanoparticles: A promising system for drug delivery. Naresuan Univ. J. 2003, 11, 51–66.

37

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. Release1993, 25, 89–98.

38

Vila, A. ; Sánchez, A. ; Tobío, M. ; Calvo, P. ; Alonso, M. J. Design of biodegradable particles for protein delivery. J. Control. Release2002, 78, 15–24.

39

Choi, W. I. ; Kamaly, N. ; Riol-Blanco, L. ; Lee, I. H. ; Wu, J. ; Swami, A. ; Vilos, C. ; Yameen, B. ; Yu, M. ; Shi, J. J. et al. A solvent-free thermosponge nanoparticle platform for efficient delivery of labile proteins. Nano Lett. 2014, 14, 6449–6455.

40

Cheon, J. W. ; Shim, C. K. ; Chung, S. J. ; Kim, D. D. Effect of tripolyphosphate (TPP) on the controlled release of cyclosporin a from chitosan-coated lipid microparticles. J. Korean Pharm. Invest. 2009, 39, 59–63.

41

Kapoor, Y. ; Dixon, P. ; Sekar, P. ; Chauhan, A. Incorporation of drug particles for extended release of Cyclosporine A from poly-hydroxyethyl methacrylate hydrogels. Eur. J. Pharm. Biopharm. 2017, 120, 73–79.

42

MacCuspie, R. I. Colloidal stability of silver nanoparticles in biologically relevant conditions. J. Nanopart. Res. 2011, 13, 2893–2908.

43

Huang, M. ; Khor, E. ; Lim, L. Y. Uptake and cytotoxicity of chitosan molecules and nanoparticles: Effects of molecular weight and degree of deacetylation. Pharm. Res. 2004, 21, 344–353.

44

Wikramanayake, T. C. ; Amini, S. ; Simon, J. ; Mauro, L. M. ; Elgart, G. ; Schachner, L. A. ; Jimenez, J. J. A novel rat model for chemotherapy-induced alopecia. Clin. Exp. Dermatol. 2012, 37, 284–289.

45

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.

46

Tong, T. ; Kim, N. ; Park, T. Topical application of oleuropein induces anagen hair growth in telogen mouse skin. PLoS One2015, 10, e0129578.

47

del Pozo-Rodríguez, A. ; Solinís, M. A. ; Gascón, A. R. ; Pedraz, J. L. Short- and long-term stability study of lyophilized solid lipid nanoparticles for gene therapy. Eur. J. Pharm. Biopharm. 2009, 71, 181–189.

48

Norouzi, M. ; Boroujeni, S. M. ; Omidvarkordshouli, N. ; Soleimani, M. Advances in skin regeneration: Application of electrospun scaffolds. Adv. Healthc. Mater. 2015, 4, 1114–1133.

49

Hasanovic, A. ; Zehl, M. ; Reznicek, G. ; Valenta, C. Chitosan-tripolyphosphate nanoparticles as a possible skin drug delivery system for aciclovir with enhanced stability. J. Pharm. Pharmacol. 2009, 61, 1609–1616.

50

Nair, S. S. Chitosan-based transdermal drug delivery systems to overcome skin barrier functions. J. Drug Deliv. Ther. 2019, 9, 266–270.

51

Sezer, A. D. ; Cevher, E. Topical drug delivery using chitosan nano- and microparticles. Expert Opin. Drug Deliv. 2012, 9, 1129–1146.

52

Roy, M. K. ; Takenaka, M. ; Kobori, M. ; Nakahara, K. ; Isobe, S. ; Tsushida, T. Apoptosis, necrosis and cell proliferation -inhibition by cyclosporine A in U937 cells (a human monocytic cell line). Pharmacol. Res. 2006, 53, 293–302.

53

Wongmekiat, O. ; Gomonchareonsiri, S. ; Thamprasert, K. Caffeic acid phenethyl ester protects against oxidative stress-related renal dysfunction in rats treated with cyclosporin A. Fundam. Clin. Pharmacol. 2011, 25, 619–626.

54

Yang, G. A. ; Chen, Q. A. ; Wen, D. ; Chen, Z. W. ; Wang, J. Q. ; Chen, G. J. ; Wang, Z. J. ; Zhang, X. D. ; Zhang, Y. Q. ; Hu, Q. Y. et al. A therapeutic microneedle patch made from hair-derived keratin for promoting hair regrowth. ACS Nano2019, 13, 4354–4360.

55

Begum, S. ; Gu, L. J. ; Lee, M. R. ; Li, Z. ; Li, J. J. ; Hossain, M. J. ; Wang, Y. B. ; Sung, C. K. In vivo hair growth-stimulating effect of medicinal plant extract on BALB/c nude mice. Pharm. Biol. 2015, 53, 1098–1103.

Nano Research
Pages 3024-3030
Cite this article:
Lee JS, Hwang Y, Oh H, et al. A novel chitosan nanocapsule for enhanced skin penetration of cyclosporin A and effective hair growth in vivo. Nano Research, 2019, 12(12): 3024-3030. https://doi.org/10.1007/s12274-019-2546-x
Topics:

934

Views

29

Crossref

N/A

Web of Science

29

Scopus

0

CSCD

Altmetrics

Received: 08 September 2019
Revised: 15 October 2019
Accepted: 16 October 2019
Published: 31 October 2019
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
Return