The treatment of the skin is challenging due to the strong barrier function of the outermost skin layer, the stratum corneum (SC). This layer is formed by dead flat cells embedded into a lipid matrix forming a lamellar structure which exhibits spacing between 6-10 nm. Drug delivery across the skin requires the modification of the tissue permeability, without promoting non-desirable effects.
The use of nanostructured lipid systems, with size small enough for passing through the narrow intercellular spaces of the SC has demonstrated to be a good alternative for skin treatment[1]. In the present work, oleic acid (OA), a skin penetration enhancer with recognized skin benefits [2] was combined with different phosphatidylcholines to form new nanostructures for topical application.
Size and polydispersity index of the nanostructures were characterized by dynamic light scattering (DLS), while shape and morphology were evaluated using cryogenic transmission electron microscopy (Cryo-TEM). Additionally, the phase behavior of the systems was determined by differential scanning calorimetry (DSC). The interaction of these systems with the skin was assessed in vitro by treatment of pig skin with Rhodamine B labeled systems and subsequent visualization of skin sections using fluorescence microscopy.
Images acquired by Cryo-TEM showed discoidal shaped structures or polyhedral vesicles depending on the constitutive molecules used (Figure 1). Average size of these systems determined by DLS was found to be around 20 and 100 nm respectively. According to DSC experiments, alkaline pH and increased amounts of OA produced a decrease in the main transition temperature of the membranes.
Fluorescence microscopy images showed a different permeation behavior of the nanostructures as a function of their composition. Overall, the main part of the molecules was retained inside the SC and follicles, while a smaller fraction was able to reach deeper layers of the skin (Figure 2).
In conclusion, the versatility of these systems and the enhancing effect of OA regarding skin permeation make evident the potential use of these nanostructures to act as delivery systems for skin and follicular applications.
[1] G. Rodríguez et al., J Biomed Nanotechnol, 11(2), 282-90, 2015.
[2] C.R. Cardoso et al., Immunobiology, 216 (3), 409–415, 2011.
