Biodegradable Nanoparticles Loaded with Levodopa and Curcumin for Treatment of Parkinson’s Disease

Abstract

Background: Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. Levodopa (L-DOPA) remains the gold-standard drug available for treating PD. Curcumin has many pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anti-amyloid, and antitumor properties. Copolymers composed of Poly (ethylene oxide) (PEO) and biodegradable polyesters such as Poly (ε-caprolactone) (PCL) can self-assemble into nanoparticles (NPs). This study describes the development of NH2–PEO–PCL diblock copolymer positively charged and modified by adding glutathione (GSH) on the outer surface, resulting in a synergistic delivery of L-DOPA curcumin that would be able to pass the blood–brain barrier. Methods: The NH2–PEO–PCL NPs suspensions were prepared by using a nanoprecipitation and solvent displacement method and coated with GSH. NPs were submitted to characterization assays. In order to ensure the bioavailability, Vero and PC12 cells were treated with various concentrations of the loaded and unloaded NPs to observe cytotoxicity. Results: NPs have successfully loaded L-DOPA and curcumin and were stable after freeze-drying, indicating advancing into in vitro toxicity testing. Vero and PC12 cells that were treated up to 72 h with various concentrations of L-DOPA and curcumin-loaded NP maintained high viability percentage, indicating that the NPs are biocompatible. Conclusions: NPs consisting of NH2–PEO–PCL were characterized as potential formulations for brain delivery of L-DOPA and curcumin. The results also indicate that the developed biodegradable nanomicelles that were blood compatible presented low cytotoxicity.

Multifunctional nanoparticle-mediated combining therapy for human diseases

“… 457 Recently, another group implemented polymeric micelles composed of polyethylene oxide and poly ε-caprolactone to co-deliver levodopa and curcumin as potential therapy for PD. 458 The system was modified with glutathione to enhance brain delivery due to its specific binding in BBB. 459 …”

Emerging Role of Plant-Based Bioactive Compounds as Therapeutics in Parkinson’s Disease

“…According to Jin et al, curcumin was found to alleviate PD by energizing the BDNF/PI3k/Akt transduction pathway [169]. Additionally, a nanoformulation of this medication plus levodopa was recently suggested for the treatment of PD [170]. In a PD model, curcumin also offers protective effects on the cerebellum [171].…”

Modulation of Macrophages Using Nanoformulations with Curcumin to Treat Inflammatory Diseases: A Concise Review

“…In addition to the therapeutic application of Cur nanoformulations in AD, the existing literature supports Cur as a small molecular drug that reduces α-synuclein (α-syn) aggregates in the treatment of PD [ 103 , 104 ]. However, its low bioavailability and difficulty in crossing the BBB to accumulate at neuronal sites are the primary issues to be addressed in the development of Cur therapeutic strategies for PD.…”