Parkinson’s disease (PD) is the most common neurodegenerative disorder after Alzheimer’s disease, affecting 1–2% of the population over 65 years old (Brakedal et al., 2022, Tysnes and Storstein, 2017) and its prevalence is rapidly increasing as the population ages. PD is characterised by the gradual degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Currently, DA replacement therapies are the first choice in PD therapeutics, with L-DOPA still considered the gold standard treatment, providing effective relief of motor symptomatology. However, L-DOPA does not stop the progression of the disease and major side effects develop while its efficacy diminishes over time.

To date, the greatest challenge in the search for new treatments for PD has been to develop strategies that allow therapeutic agents to cross the blood-brain barrier (BBB). The BBB is a physiological barrier in the brain that controls the movement of substances between the brain and the rest of the body by preventing most molecules from reaching the brain (Cheng et al., 2022, Eltanameli et al., 2022, Karthivashan et al., 2020). The BBB presents a low and selective permeability and prevents the entry of nearly all large molecules and 98% of small molecules into the brain (Cheng et al., 2022, Pandian et al., 2022). Different parameters can determine the passage of molecules throughout the BBB, such as molecular weight, size, shape, ionisation state, lipophilicity, and plasma-protein binding affinity (Eltanameli et al., 2022). Several transporters and surface receptors are found in the BBB to facilitate the unidirectional movement of large and hydrophilic molecules across it, while lipophilic substances can easily enter the brain parenchyma through transcytosis (Cheng et al., 2022, Karthivashan et al., 2020).

The protective nature of the BBB limits the entry of therapeutic molecules and challenges the design of effective anti-PD drugs (Cheng et al., 2022, Jagaran and Singh, 2022). Thus, scientific interest is now focused on developing different strategies, invasive and non-invasive, to allow drugs to cross the BBB (Cheng et al., 2022, Pandian et al., 2022).