Development of sublingual films and electrospun nanofibers of pramipexole for the immediate relief of dyskinesias in Parkinson's disease.

Oral levodopa/carbidopa tablets remain the gold standard therapy for Parkinson's disease; however, long-term administration of these drugs has been associated with dyskinesias and "on-off" motor fluctuations. Non-ergot dopaminergic agonists such as pramipexole (PPX) have been proposed to mitigate these complications. Another common problem found in these patients is dysphagia, encouraging studies with alternative administration routes. In this context, this study aimed to develop polymeric films and nanofibers for the sublingual delivery of PPX. Polyvinyl alcohol (PVA) matrices, with or without chitosan (CH), were prepared by electrospinning and solvent casting techniques. Electrospun fibers exhibited greater elongation at break, enhanced hydration and faster disintegration than cast films. Incorporation of CH led to smaller fiber diameters (300 ± 70 nm) than CH-free nanofibers (513 ± 105 nm). Cast films (57.3 % to 74.82 %) provided faster PPX release than electrospun fibers (35.57 % to 48.87 %) within 75 s. The presence of CH in nanofibers reduced the mucoadhesion due to stronger chemical interactions between the polymers, also explaining the lower sublingual permeability of CH nanofibers compared to CH cast films (5.98 vs. 18.95 µg/cm2, respectively). In future studies, cast films should be prioritized due to increased mucoadhesion, release rate and sublingual permeability. Taken together, these effects would contribute to an immediate relief of motor symptoms in patients with Parkinson's disease. Further pharmacokinetics studies in humans are needed to confirm the benefits suggested here.