Abstract
Over the past years, hair follicles have gained a lot of interest in the field of skin penetration research as they represent an important penetration pathway for topically applied substances. They function as reservoirs [1, 2] and also as portals of entry to the viable skin layers [3]. Under physiological conditions the intact stratum corneum significantly impairs skin penetration, especially of large hydrophilic molecules and particulate structures. Hair follicles, in contrast, represent interruptions in this barrier and the importance of the transfollicular route of penetration has been demonstrated by several independent studies on various animal skin models, where hairy skin was compared with hair follicle-free skin areas [4, 5]. The role of the follicular penetration pathway compared to transepidermal route was also demonstrated by selective blockage of the follicular orifices in porcine ear skin [6] as well as human skin explants [7]. In vivo experiments with caffeine applied as shampoo formulations on skin with open or sealed hair follicles further underlined the importance of hair follicles for the transdermal permeation and systemic delivery of hydrophilic drugs [8]. The follicular route seems to be of special importance for particle penetration in skin. Particulate structures ranging from liposomes to solid inorganic particles and microspheres up to a diameter of 10 μm were shown to aggregate and remain in hair follicle openings. Such observations provided the basis for the idea of hair follicle targeting with particulate drug carriers [9]. Modifications of nanoparticle physicochemical properties, use of permeabilizing agents, as well as partial removal of the stratum corneum are some of the methods which were shown to increase the hair follicle penetration of drug-loaded nanoparticles as well as their targeting ability [10, 11]. In the following chapter, we outline how hair follicles act as entry pathway and reservoir structure for topically applied particles. We review the penetration properties of specific particle types and the influence of hair follicle parameters, e.g., hair follicle types, growth activity, and sebum production as modifying factors of particle–skin interactions. In fact, studies by our group and others strongly suggest that the hair follicle provides an important interface for such interactions. Nanoparticle-based hair follicle targeting aims at utilizing these interactions for therapeutic purposes, e.g., to deliver functionalized particles loaded with active compounds selectively to the hair follicles or even to specific skin compartments and cell populations. Particle-based targeting of hair follicles may include deposition of active compounds in the follicular reservoir, targeting of active compounds to specific compartments within the follicular duct, e.g., sebaceous gland, stem cell region, or even targeting of specific cell populations such as perifollicular antigen-presenting cells (Fig. 9.1).
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References
Blume-Peytavi U, Vogt A. Human hair follicle: reservoir function and selective targeting. Br J Dermatol. 2011;165 Suppl 2:13–7.
Papakostas D, Rancan F, Sterry W, Blume-Peytavi U, Vogt A. Nanoparticles in dermatology. Arch Dermatol Res. 2011;303(8):533–50.
Mitragotri S. Modeling skin permeability to hydrophilic and hydrophobic solutes based on four permeation pathways. J Control Release. 2003;86(1):69–92.
Lademann J, Knorr F, Richter H, et al. Hair follicles—an efficient storage and penetration pathway for topically applied substances. Summary of recent results obtained at the Center of Experimental and Applied Cutaneous Physiology, Charite-Universitatsmedizin Berlin, Germany. Skin Pharmacol Physiol. 2008;21(3):150–5.
Mahe B, Vogt A, Liard C, et al. Nanoparticle-based targeting of vaccine compounds to skin antigen-presenting cells by hair follicles and their transport in mice. J Invest Dermatol. 2009;129(5):1156–64.
Grams YY, Whitehead L, Cornwell P, Bouwstra JA. Time and depth resolved visualisation of the diffusion of a lipophilic dye into the hair follicle of fresh unfixed human scalp skin. J Control Release. 2004;98(3):367–78.
Lademann J, Otberg N, Richter H, et al. Investigation of follicular penetration of topically applied substances. Skin Pharmacol Appl Skin Physiol. 2001;14 Suppl 1:17–22.
Otberg N, Teichmann A, Rasuljev U, Sinkgraven R, Sterry W, Lademann J. Follicular penetration of topically applied caffeine via a shampoo formulation. Skin Pharmacol Physiol. 2007;20(4):195–8.
Vogt A, Mandt N, Lademann J, Schaefer H, Blume-Peytavi U. Follicular targeting—a promising tool in selective dermatotherapy. J Investig Dermatol Symp Proc. 2005;10(3):252–5.
Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov. 2004;3(2):115–24.
Morrow DI, Garland MJ, McCarron PA, Woolfson AD, Donnelly RF. Innovative drug delivery strategies for topical photodynamic therapy using porphyrin precursors. J Environ Pathol Toxicol Oncol. 2007;26(2):105–16.
Lademann J, Richter H, Teichmann A, et al. Nanoparticles—an efficient carrier for drug delivery into the hair follicles. Eur J Pharm Biopharm. 2007;66(2):159–64.
Rolland A, Wagner N, Chatelus A, Shroot B, Schaefer H. Site-specific drug delivery to pilosebaceous structures using polymeric microspheres. Pharm Res. 1993;10(12):1738–44.
Sellheyer K, Krahl D. Skin mesenchymal stem cells: prospects for clinical dermatology. J Am Acad Dermatol. 2010;63(5):859–65.
Nishikawa-Torikai S, Osawa M, Nishikawa S. Functional characterization of melanocyte stem cells in hair follicles. J Invest Dermatol. 2011;131(12):2358–67.
Wang X, Tredget EE, Wu Y. Dynamic signals for hair follicle development and regeneration. Stem Cells Dev. 2012;21(1):7–18.
Vogt A, McElwee K, Blume-Peytavi U. Biology of the hair follicle. In: Blume-Peytavi U, Tosti A, Whiting D, Trueb R, eds. Textbook on Hair – From basic science to clinical application. Germay: Springer; 2008:1–22.
Vogt A, Hadam S, Heiderhoff M, et al. Morphometry of human terminal and vellus hair follicles. Exp Dermatol. 2007;16(11):946–50.
Toll R, Jacobi U, Richter H, Lademann J, Schaefer H, Blume-Peytavi U. Penetration profile of microspheres in follicular targeting of terminal hair follicles. J Invest Dermatol. 2004;123(1):168–76.
Vogt A, Combadiere B, Hadam S, et al. 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after transcutaneous application on human skin. J Invest Dermatol. 2006;126(6):1316–22.
Knorr F, Lademann J, Patzelt A, Sterry W, Blume-Peytavi U, Vogt A. Follicular transport route—research progress and future perspectives. Eur J Pharm Biopharm. 2009;71(2):173–80.
Hordinsky M. Advances in hair diseases. Adv Dermatol. 2008;24:245–59.
Meidan VM, Touitou E. Treatments for androgenetic alopecia and alopecia areata: current options and future prospects. Drugs. 2001;61(1):53–69.
Ohnemus U, Uenalan M, Inzunza J, Gustafsson JA, Paus R. The hair follicle as an estrogen target and source. Endocr Rev. 2006;27(6):677–706.
Zouboulis CC, Bornstein SR. Endocrinology of the skin—a promising joint adventure. Horm Metab Res. 2007;39(2):69–70.
Rancan F, Papakostas D, Hadam S, et al. Investigation of polylactic acid (PLA) nanoparticles as drug delivery systems for local dermatotherapy. Pharm Res. 2009;26(8):2027–36.
Meidan VM, Bonner MC, Michniak BB. Transfollicular drug delivery—is it a reality? Int J Pharm. 2005;306(1–2):1–14.
Teichmann A, Heuschkel S, Jacobi U, et al. Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an o/w microemulsion and an amphiphilic cream. Eur J Pharm Biopharm. 2007;67(3):699–706.
Wu H, Ramachandran C, Weiner ND, Roessler BJ. Topical transport of hydrophilic compounds using water-in-oil nanoemulsions. Int J Pharm. 2001;220(1–2):63–75.
Grice JE, Ciotti S, Weiner N, Lockwood P, Cross SE, Roberts MS. Relative uptake of minoxidil into appendages and stratum corneum and permeation through human skin in vitro. J Pharm Sci. 2010;99(2):712–8.
Huang Y, Yu F, Park YS, et al. Co-administration of protein drugs with gold nanoparticles to enable percutaneous delivery. Biomaterials. 2010;31(34):9086–91.
Munster U, Nakamura C, Haberland A, et al. RU 58841-myristate—prodrug development for topical treatment of acne and androgenetic alopecia. Pharmazie. 2005;60(1):8–12.
Chen H, Chang X, Du D, et al. Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting. J Control Release. 2006;110(2):296–306.
Jung S, Otberg N, Thiede G, et al. Innovative liposomes as a transfollicular drug delivery system: penetration into porcine hair follicles. J Invest Dermatol. 2006;126(8):1728–32.
Danhier F, Feron O, Preat V. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148(2):135–46.
Alvarez-Roman R, Naik A, Kalia YN, Guy RH, Fessi H. Skin penetration and distribution of polymeric nanoparticles. J Control Release. 2004;99(1):53–62.
Zvyagin AV, Zhao X, Gierden A, Sanchez W, Ross JA, Roberts MS. Imaging of zinc oxide nanoparticle penetration in human skin in vitro and in vivo. J Biomed Opt. 2008;13(6):064031.
Baroli B, Ennas MG, Loffredo F, Isola M, Pinna R, Lopez-Quintela MA. Penetration of metallic nanoparticles in human full-thickness skin. J Invest Dermatol. 2007;127(7):1701–12.
Mortensen LJ, Oberdorster G, Pentland AP, Delouise LA. In vivo skin penetration of quantum dot nanoparticles in the murine model: the effect of UVR. Nano Lett. 2008;8(9):2779–87.
Graf C, Meinke M, Gao Q, et al. Qualitative detection of single submicron and nanoparticles in human skin by scanning transmission x-ray microscopy. J Biomed Opt. 2009;14(2):021015.
Rancan F, Todorova A, Hadam S, et al. Stability of polylactic acid particles and release of fluorochromes upon topical application on human skin explants. Eur J Pharm Biopharm. 2012;80(1):76–84.
Zouboulis CC, Eady A, Philpott M, et al. What is the pathogenesis of acne? Exp Dermatol. 2005;14(2):143–52.
Gollnick H, Cunliffe W, Berson D, et al. Management of acne: a report from a Global Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003;49(1 Suppl):S1–37.
Leyden JJ. Topical treatment of acne vulgaris: retinoids and cutaneous irritation. J Am Acad Dermatol. 1998;38(4):S1–4.
Mordon S, Sumian C, Devoisselle JM. Site-specific methylene blue delivery to pilosebaceous structures using highly porous nylon microspheres: an experimental evaluation. Lasers Surg Med. 2003;33(2):119–25.
Honzak L, Sentjurc M. Development of liposome encapsulated clindamycin for treatment of acne vulgaris. Pflugers Arch. 2000;440(5 Suppl):R44–5.
Bhalerao SS, Raje Harshal A. Preparation, optimization, characterization, and stability studies of salicylic acid liposomes. Drug Dev Ind Pharm. 2003;29(4):451–67.
Manconi M, Sinico C, Valenti D, Lai F, Fadda AM. Niosomes as carriers for tretinoin: III. A study into the in vitro cutaneous delivery of vesicle-incorporated tretinoin. Int J Pharm. 2006;311(1–2):11–9.
Schafer-Korting M, Korting HC, Ponce-Poschl E. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig. 1994;72(12):1086–91.
Bernard E, Dubois JL, Wepierre J. Importance of sebaceous glands in cutaneous penetration of an antiandrogen: target effect of liposomes. J Pharm Sci. 1997;86(5):573–8.
Mehnert W, Mader K. Solid lipid nanoparticles: production, characterization and applications. Adv Drug Deliv Rev. 2001;47(2–3):165–96.
Schafer-Korting M, Mehnert W, Korting HC. Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev. 2007;59(6):427–43.
Date AA, Naik B, Nagarsenker MS. Novel drug delivery systems: potential in improving topical delivery of antiacne agents. Skin Pharmacol Physiol. 2006;19(1):2–16.
James KA, Burkhart CN, Morrell DS. Emerging drugs for acne. Expert Opin Emerg Drugs. 2009;14(4):649–59.
Stewart ME, Downing DT, Cook JS, Hansen JR, Strauss JS. Sebaceous gland activity and serum dehydroepiandrosterone sulfate levels in boys and girls. Arch Dermatol. 1992;128(10):1345–8.
Thiboutot D, Harris G, Iles V, Cimis G, Gilliland K, Hagari S. Activity of the type 1 5 alpha-reductase exhibits regional differences in isolated sebaceous glands and whole skin. J Invest Dermatol. 1995;105(2):209–14.
Stecova J, Mehnert W, Blaschke T, et al. Cyproterone acetate loading to lipid nanoparticles for topical acne treatment: particle characterisation and skin uptake. Pharm Res. 2007;24(5):991–1000.
Tabbakhian M, Tavakoli N, Jaafari MR, Daneshamouz S. Enhancement of follicular delivery of finasteride by liposomes and niosomes 1. In vitro permeation and in vivo deposition studies using hamster flank and ear models. Int J Pharm. 2006;323(1–2):1–10.
Kumar R, Singh B, Bakshi G, Katare OP. Development of liposomal systems of finasteride for topical applications: design, characterization, and in vitro evaluation. Pharm Dev Technol. 2007;12(6):591–601.
Hibberts NA, Howell AE, Randall VA. Balding hair follicle dermal papilla cells contain higher levels of androgen receptors than those from non-balding scalp. J Endocrinol. 1998;156(1):59–65.
Price VH. Testosterone metabolism in the skin. A review of its function in androgenetic alopecia, acne vulgaris, and idiopathic hirsutism including recent studies with antiandrogens. Arch Dermatol. 1975;111(11):1496–502.
Kaur IP, Kakkar S. Topical delivery of antifungal agents. Expert Opin Drug Deliv. 2010;7(11):1303–27.
Souto EB, Muller RH. SLN and NLC for topical delivery of ketoconazole. J Microencapsul. 2005;22(5):501–10.
Souto EB, Wissing SA, Barbosa CM, Muller RH. Development of a controlled release formulation based on SLN and NLC for topical clotrimazole delivery. Int J Pharm. 2004;278(1):71–7.
Souto EB, Muller RH. The use of SLN and NLC as topical particulate carriers for imidazole antifungal agents. Pharmazie. 2006;61(5):431–7.
Sanna V, Gavini E, Cossu M, Rassu G, Giunchedi P. Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: in-vitro characterization, ex-vivo and in-vivo studies. J Pharm Pharmacol. 2007;59(8):1057–64.
Bachhav YG, Mondon K, Kalia YN, Gurny R, Moller M. Novel micelle formulations to increase cutaneous bioavailability of azole antifungals. J Control Release. 2011;153(2):126–32.
Schwartz JR, Shah R, Krigbaum H, Sacha J, Vogt A, Blume-Peytavi U. New insights on dandruff/seborrhoeic dermatitis: the role of the scalp follicular infundibulum in effective treatment strategies. Br J Dermatol. 2011;165 Suppl 2:18–23.
Lademann J, Richter H, Schanzer S, et al. Penetration and storage of particles in human skin: perspectives and safety aspects. Eur J Pharm Biopharm. 2011;77(3):465–8.
Lademann J, Richter H, Schaefer UF, et al. Hair follicles—a long-term reservoir for drug delivery. Skin Pharmacol Physiol. 2006;19(4):232–6.
Combadiere B, Liard C. Transcutaneous and intradermal vaccination. Hum Vaccin. 2011;7(8):811–27.
Kanchan V, Panda AK. Interactions of antigen-loaded polylactide particles with macrophages and their correlation with the immune response. Biomaterials. 2007;28(35):5344–57.
Combadiere B, Vogt A, Mahe B, et al. Preferential amplification of CD8 effector-T cells after transcutaneous application of an inactivated influenza vaccine: a randomized phase I trial. PLoS One. 2010;5(5):e10818.
Liard C, Munier S, Arias M, et al. Targeting of HIV-p24 particle-based vaccine into differential skin layers induces distinct arms of the immune responses. Vaccine. 2011;29(37):6379–91.
Alkhalifah A. Topical and intralesional therapies for alopecia areata. Dermatol Ther. 2011;24(3):355–63.
Nakamura M, Jo J, Tabata Y, Ishikawa O. Controlled delivery of T-box21 small interfering RNA ameliorates autoimmune alopecia (Alopecia Areata) in a C3H/HeJ mouse model. Am J Pathol. 2008;172(3):650–8.
Domashenko A, Gupta S, Cotsarelis G. Efficient delivery of transgenes to human hair follicle progenitor cells using topical lipoplex. Nat Biotechnol. 2000;18(4):420–3.
Li L, Hoffman RM. The feasibility of targeted selective gene therapy of the hair follicle. Nat Med. 1995;1(7):705–6.
Branski LK, Masters OE, Herndon DN, et al. Pre-clinical evaluation of liposomal gene transfer to improve dermal and epidermal regeneration. Gene Ther. 2010;17(6):770–8.
Hachiya A, Sriwiriyanont P, Patel A, et al. Gene transfer in human skin with different pseudotyped HIV-based vectors. Gene Ther. 2007;14(8):648–56.
Zhao M, Saito N, Li L, et al. A novel approach to gene therapy of albino hair in histoculture with a retroviral streptomyces tyrosinase gene. Pigment Cell Res. 2000;13(5):345–51.
Franzen S. A comparison of peptide and folate receptor targeting of cancer cells: from single agent to nanoparticle. Expert Opin Drug Deliv. 2011;8(3):281–98.
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Rancan, F., Afraz, Z., Combadiere, B., Blume-Peytavi, U., Vogt, A. (2013). Hair Follicle Targeting with Nanoparticles. In: Nasir, A., Friedman, A., Wang, S. (eds) Nanotechnology in Dermatology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5034-4_9
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