Self-assembled polydopamine nanoparticles improve treatment in Parkinson's disease model mice and suppress dopamine-induced dyskinesia

• Published in: Acta biomaterialia Vol. 109; pp. 220 - 228
• Main Authors: Vong, Long Binh, Sato, Yuna, Chonpathompikunlert, Pennapa, Tanasawet, Supita, Hutamekalin, Pilaiwanwadee, Nagasaki, Yukio
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2020; Elsevier BV
• Subjects: Animal models; Animals; BBB; Block copolymers; Cattle; Cell Line; Dihydroxyphenylalanine; Disease Models, Animal; Dopamine; Dopamine delivery; Dyskinesia; Dyskinesias - prevention & control; Hydrophobicity; Indoles - chemical synthesis; Indoles - pharmacokinetics; Indoles - therapeutic use; Indoles - toxicity; Levodopa; Levodopa - pharmacokinetics; Male; Medical treatment; Mice, Inbred C57BL; Mice, Inbred ICR; Movement disorders; MPTP; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Nanoparticles - toxicity; Neurodegenerative diseases; Neurotoxicity; Parkinson Disease - drug therapy; Parkinson's disease; Poly(l-DOPA); Polymer micelle-prodrug; Polymers - chemical synthesis; Polymers - pharmacokinetics; Polymers - therapeutic use; Polymers - toxicity; Precursors; Self-assembled drug; Self-assembly; Signs and symptoms; Toxicity; Self-assembled drug; Parkinson's disease; BBB; Dopamine delivery; Poly(l-DOPA); Polymer micelle-prodrug
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2020.03.021

Although Levodopa (l-DOPA), a dopamine precursor, exhibits a high risk of dyskinesia, it remains the primary treatment in Parkinson's disease (PD), a progressive neurodegenerative disorder. In this study, we designed poly(l-DOPA)-based self-assembled nanodrug (NanoDOPA) from amphiphilic block copolymer possessing poly(l-DOPA(OAc)2), which is a precursor of l-DOPA as a hydrophobic segment, for treatment in a PD model mouse. Under physiological enzyme treatment, the poly(l-DOPA(OAc)2) in the block copolymer was hydrolyzed to liberate l-DOPA gradually. Using the MPTP-induced PD mouse model, we observed that mice treated with NanoDOPA demonstrated a significant improvement of PD symptoms compared to the l-DOPA treatment. Interestingly, the NanoDOPA treatment did not cause the dyskinesia symptoms, which was clearly observed in the l-DOPA-treated mice. Furthermore, NanoDOPA exhibited remarkably lower toxicity in vitro compared to l-DOPA, in addition with no noticeable NanoDOPA toxicity observed in the treated mice. These results suggested that self-assembled NanoDOPA is a promising therapeutic in the treatment of PD. In this study, we proposed a therapeutic approach for the effective treatment of Parkinson's disease (PD) using newly designed poly(l-DOPA)-based self-assembled nanodrug (NanoDOPA) prepared from amphiphilic block copolymers possessing poly(l-DOPA(OAc)2), which is a precursor of l-DOPA as a hydrophobic segment, for treatment in a PD model mouse. Under physiological enzyme treatments, NanoDOPA was hydrolyzed to liberate l-DOPA gradually, improving the pharmacokinetic value of l-DOPA. The mice treated with NanoDOPA significantly improved PD symptoms compared to the l-DOPA treatment in a neurotoxin-induced PD mouse model. Interestingly, NanoDOPA treatment did not cause dyskinesia symptoms, which was observed in the l-DOPA-treated mice. The obtained results in this study suggested that self-assembled NanoDOPA is a promising therapeutic in the treatment of PD. [Display omitted]