Formulation and characterisation of resveratrol-loaded nanostructured lipid carriers for use in combination with scalp cooling therapy to mitigate chemotherapy-induced follicular cytotoxicity and hair loss

Hair loss represents a highly traumatic side-effect of chemotherapy treatment, it significantly affects psychological well-being, self-esteem and quality-of-life, with the fear of alopecia causing severe anxiety for cancer patients. While effective in eliminating cancer cells, chemotherapy drugs collaterally damage hair follicles resulting in chemotherapy-induced alopecia (CIA). Scalp cooling is a breakthrough treatment for patients, being the only clinically proven method to prevent CIA, with 50-65% of patients experiencing low grade alopecia (thus negating use of head covers and/or wigs during treatment). Our recent biological studies showed that optimal cooling effectively protects cells in human hair follicles from chemotherapy drug-mediated damage, whereas suboptimal cooling is less effective. However, combining cooling with an antioxidant that blocks reactive oxygen species (ROS) restores this protective effect against chemotherapy-induced hair follicle damage. In this study we focused on encapsulating the antioxidant resveratrol (RV) in nanostructured lipid carriers (NLCs) to optimise follicular targeting as a precursor to scalp cooling. We aimed for a particle size above 200 nm to limit systemic absorption and found that the nanoparticles had the desired properties when formulated with propylene glycol dicaprylate as the liquid lipid. RV-loaded NLCs remained stable at 4°C for > 6 months, with less than 10% variation in their size, polydispersity index (PDI), and zeta potential (ZP). Transmission electron microscopy (TEM) confirmed formation of Type I NLCs, featuring imperfect crystals that suggest a disordered lattice, facilitating RV's presence as disordered crystals or amorphous clusters within the matrix. Skin deposition studies demonstrated that RV-loaded NLCs reach the follicular reservoir within 6 hours, confirming their potential for co-application with scalp cooing for combating CIA.