Systemic drug delivery often takes place through the skin due to its ease of use and better patient compliance. However, the outermost layer of the skin, the stratum corneum (SC) poses a significant barrier to drug application. The SC consists of enucleated dead cells that are surrounded by a lipid matrix, which constitutes a major limitation in the rate of drug diffusion. To maximise drug penetration through the SC, it is vital to comprehend the interaction of drug carriers with SC lipids. Towards this goal, scientists of the EU-funded NANOLEM (Understanding the physico-chemical basis of transdermal drug delivery using nanomaterials) project utilised model lipid membranes, which mimicked many aspects of skin lipid organisation. The primary objective was to investigate the mechanisms involved in the interactions between dermal membranes and nanogels, one of the most effective drug delivery systems. Scientists used N-isopropylacrylamide (NIPAM) as the monomer to generate various nanogels and optimised their size, particle rigidity and transition temperature. The generated nanogels were tested in various skin models based on ceramides, cholesterol and fatty acid mixtures or lipid bilayers. Both neutral and charged nanogels were screened for their efficiency to penetrate these lipid surfaces. Overall, the presence of fatty acids was critical in the formation of complexes and transport of nanogels. As expected, researchers envisage the type of body part and dermal condition to be important in the permeability to nanogels. Next, scientists discovered that the encapsulation efficiency of drugs depended on the structure of nanogels but did not affect nanogel size or morphology. The consensus was that particles with higher hydrophobicity and ability to adapt their conformation were the best candidates for effective transdermal transport. Taken together, the NANOLEM study performed a thorough investigation into nanoparticle-based dermal delivery systems. At the same time, it emphasised the need for future risk assessment of skin exposure to nanoparticles.
Nanoparticles, drug delivery, skin, NANOLEM, N-isopropylacrylamide, nanogel