Hair Follicle Targeting with Nanoparticles

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).