Enhancing the transdermal penetration of nanoconstructs: could hyaluronic acid be the key?

Nanoconstructs, such as liposomes, polymeric micelles, gold nanoparticles, carbon nanomaterials and nanocrystalline quantum dots, have been widely investigated for diagnostic, bioimaging and therapeutic applications [1]. Nanoconstructs have been also extensively explored in the field of dermatology. For example, liposomes and polymeric nanoparticles loaded with drugs were applied as topical administration agents for the treatment of skin diseases such as psoriasis, dermatitis and skin cancer [2,3]. Titanium dioxide and zinc oxide (ZnO) nanoparticles have been used as sun-screen formulation for the protection of skin from UV by the scattering, absorption and reflection of UV [4]. Silver nanoparticles are commercially used as wound and burn dressing agents with antibacterial effects [5]. Quantum dots and ZnO nanoparticles were utilized as bioimaging agents for the diagnosis of skin diseases [6,7]. Moreover, gold nanoconstructs and carbon nanomaterials have been actively investigated as promising agents for the photothermal ablation therapy of skin cancers due to their high light-to-heat conversion capability [8,9]. For further applications of nanoconstructs in dermatology, we need efficient transdermal delivery carriers of the nanoconstructs. The transdermal delivery has several advantages over other administration routes, such as oral delivery and needle based injection. The advantages include noninvasive treatment, self-administration, improved patient compliance and avoidance of hepatic first-pass metabolism or digestion system [10]. Despite these benefits, the low skin permeability of nanoconstructs such as polymers, proteins, hydrophilic drugs and nanoparticles limited their wide applications to the transdermal delivery. To facilitate the transdermal delivery of nanoconstructs, additional treatments have been adopted using penetration enhancers, iontophoresis, ultrasound and microneedles [11]. However, these methods require physical perturbations to the skin tissue, causing skin damage in some cases [12]. A noninvasive molecular carrier for transdermal delivery would have compelling advantages. The understanding for the characteristics of skin layers can be a good starting point for the development of transdermal delivery carriers of nanoconstructs. Stratum corneum (SC), the outermost skin layer, is the main barrier composed of densely packed dead cells forming hydrophobic surfaces. For the penetration of hydrophobic SC, hydrophobic molecules have clear benefits over hydrophilic molecules. The hydrophobic molecules can infiltrate into densely packed lipid layers in SC. However, nanoconstructs are usually formulated to have hydrophilic surfaces enhancing the physiological stability in the biological conditions. This contradicting requirement of hydrophobicity and hydrophilicity for transdermal delivery should be reconciled to enhance the physiological stability and the skin permeability by lipid disruption in SC. Recently, hyaluronic acid (HA) has been investigated as a promising transdermal delivery carrier. HA is a naturally occurring linear polysaccharide composed of repeating units of d-glucuronic acid and N-acetylEnhancing the transdermal penetration of nanoconstructs: could hyaluronic acid be the key?