Advancing Parkinson's Disease Treatment: Overcoming Blood-Brain Barrier Challenges with Polymeric Micelles
Abstract
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Pathophysiology of Parkinson's disease (PD) is characterized by significant barriers to effective pharmacotherapy, primarily due to the limitation of the intact blood-brain barrier (BBB), the rapid metabolism of drug substances in the body, and the low bioavailability of most drugs. Traditional treatments, such as levodopa and dopamine agonists, provide temporary symptomatic relief and have limited half-lives and peripheral side effects, as well as strongly inconsistent plasma concentrations. Such drawbacks have spurred interest in nanocarrier-based drug delivery systems, which could offer targeted, prolonged neurotherapeutic delivery to the central nervous system. Polymeric micelles (PMs) are considered versatile and are mainly used due to their nanoscale size, biocompatibility, adaptable core-shell structure, and ability to entrap hydrophobic and hydrophilic molecules. The current study focused on the design, development, and evaluation of PM-based delivery to PD (especially rotigotine-loaded micelles and multifunctional structures that simultaneously provide antioxidants or neuroprotective factors). Furthermore, the study described essential formulation approaches, including ligand-functionalized surfaces to target the BBB, pH- or redox-controlled drug release, and intranasal delivery. The study discussed these methods in terms of improving drug localization and extending the treatment's effects in the brain. Although pre-clinical research has demonstrated high potential, the clinical implementation of PM-based systems remains limited by scalability challenges, regulatory ambiguity, and limited availability of long-term safety data. However, when such difficulties are overcome through standardized characterization, stringent pharmacokinetic analysis, and improved approval pathways, PMs could be a viable solution for a sustained, targeted, and possibly disease-modifying treatment in PD.
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