Nanotechnology-enabled Bromocriptine Delivery for Parkinson's Disease: Overcoming Pharmacokinetic Barriers and Advancing Brain Targeting

Bromocriptine (BRC) is a semi-synthetic ergot alkaloid and potent dopamine D2 receptor agonist used to manage a variety of dopamine dysfunction disorders. Over the past few decades, BRC has been used therapeutically for metabolic, endocrinological, and neurological disorders. Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopaminergic neurons in the substantia nigra degenerate, depleting the striatum of dopamine. Globally, PD affects nearly 1% of individuals over 60 years of age, with its prevalence increasing as age advances. BRC exerts its therapeutic effects primarily through stimulation of dopamine D2 receptors, thereby modulating dopaminergic signalling and reducing the functional consequences of dopamine depletion. BRC could be used alone or as an adjunct with levodopa to reduce levodopa-induced dyskinesia and motor fluctuations. However, BRC has significant pharmacokinetic limitations, including poor oral absorption (28%) and low bioavailability (6%), due to its high lipophilicity, plasma protein binding, and first-pass metabolism.

A comprehensive literature search was carried out using databases including PubMed, Scopus, and Google Scholar (January 2008-June 2026) using various keywords such as 'bromocriptine', 'nanoparticle', 'nanoformulation', 'blood-brain barrier', and 'Parkinson's disease' to identify and critically appraise bromocriptine-specific nanocarrier studies.

In order to overcome the challenges associated with BRC delivery, nanoformulations have emerged as promising drug-delivery strategies. Lipid-based nanoparticles, including solid lipid nanoparticles and nanostructured lipid carriers, have shown potential to improve drug bioavailability. Numerous studies have shown that nanoemulsions have improved solubility and overcome brain targeting challenges. However, clinical studies are needed to determine whether the benefits observed with these nanoformulations can translate into clinically meaningful outcomes.