L. Vong, Yuna Sato, Pennapa Chonpathompikunlert, Supita Tanasawet, P. Hutamekalin, Y. Nagasaki
{"title":"Self-Assembled Polydopamine Nanoparticles Improve Treatment in Parkinson's Disease Model Mice and Suppress Dopamine-Induced Dyskinesia","authors":"L. Vong, Yuna Sato, Pennapa Chonpathompikunlert, Supita Tanasawet, P. Hutamekalin, Y. Nagasaki","doi":"10.2139/ssrn.3539216","DOIUrl":null,"url":null,"abstract":"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. Statement of significance In this study, we proposed a therapeutic approach for the effective treatment of Parkinson 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-assembly NanoDOPA is a promising therapeutic in the treatment of PD.","PeriodicalId":105746,"journal":{"name":"AMI: Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2020-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"32","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AMI: Acta Biomaterialia","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2139/ssrn.3539216","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 32
Abstract
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. Statement of significance In this study, we proposed a therapeutic approach for the effective treatment of Parkinson 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-assembly NanoDOPA is a promising therapeutic in the treatment of PD.