Nanoparticles Mediating the Sustained Puerarin Release Facilitate Improved Brain Delivery to Treat Parkinson’s Disease

Abstract

Recent work has highlighted the potential of puerarin (PU) as a valuable compound to treat Parkinson’s disease (PD), but its undesirable water solubility and bioavailability have constrained its utility. In this study, we sought to develop nanoparticles (NPs) that could be used to encapsulate PU, thereby extending its in vivo half-life and improving its bioavailability and accumulation in the brain to treat the symptoms of PD. We prepared spherical NPs (88.36 ± 1.67 nm) from six-armed star-shaped poly­(lactide-co-glycolide) (6-s-PLGA) NPs that were used to encapsulate PU (PU-NPs) with 89.52 ± 1.74% encapsulation efficiency, 42.97 ± 1.58% drug loading, and a 48 h sustained drug release. NP formation and drug loading were largely mediated by hydrophobic interactions, while changes in the external environment led these NPs to become increasingly hydrophilic, thereby leading to drug release. Relative to PU alone, PU-NPs exhibited significantly improved cellular internalization, permeation, and neuroprotective effects. Upon the basis of Förster resonance energy transfer (FRET) of NPs-administered zebrafish, we were able to determine that these NPs were rapidly absorbed into circulation whereupon they were able to access the brain. We further conducted oral PU-NPs administration to rats, revealing significant improvements in PU accumulation within the plasma and brain relative to rats administered free PU. In MPTP-mediated neurotoxicity in mice, we found that PU-NPs treatment improved disease-associated behavioral deficits and depletion of dopamine and its metabolites. These findings indicated that PU-NPs represent a potentially viable approach to enhancing PU oral absorption, thus improving its delivery to the brain wherein it can aid in the treatment of PD.

Nanoparticles Prepared From Pterostilbene (PTE): A New Strategy for Reducing Blood Glucose and Improving Diabetic Complications

“…However, the EE of insulin NPs prepared by MumuniMA [43] et al with chitosan and water-soluble snail mucin is 88.6%. Chen [44] prepared spherical NPs from six-armed starshaped poly(lactide-co-glycolide)(6-s-PLGA) NPs that were used to encapsulate puerarin (PU-NPs). Its EE had 89.52 ± 1.74% and LC had 42.97 ± 1.58%.…”

Polymeric Nanoparticles-Based Brain Delivery with Improved Therapeutic Efficacy of Ginkgolide B in Parkinson’s Disease

“…Next, GB-NPs were prepared via an antisolvent precipitation and stabilizer-based approach. 15 Briefly, we injected 0.2 mL volumes of GB and PEG-PCL (20 mg/mL in acetone) into a 10 mL volume of dH 2 O containing the stabilizer F68 (0.5 mg/ mL). This solution was constantly stirred at 1000 rpm at room temperature.…”

“…14 For the treatment of PD, NPs <100 nm in size are ideal as they have been shown to be well suited to delivering cargos through the brain capillary endothelial cell layer. 15 Therapeutically viable NPs also need to be capable of achieving sustained drug release in vivo in order to effectively treat chronic conditions such as PD. Therefore, in this study, we endeavored to develop small NPs capable of releasing GB in a sustained fashion in order to achieve anti-Parkinsonian efficacy.…”

“…16 We have successfully developed six-armed star-shaped NPs to deliver drugs across the BBB. 15 However, the endocytic mechanisms responsible for the uptake and transport of such NPs remain uncertain. To that end, we explored the endocytic mechanisms of NPs in Madin-Darby canine kidney (MDCK) cells, as these cells represent an ideal in vitro epithelial model owing to their polarity, tight junction formation, and relatively thin mucus layer.…”

Puerarin inhibits titanium particle‐induced osteolysis and RANKL‐induced osteoclastogenesis via suppression of the NF‐κB signaling pathway

“…Puerarin, which comes from the herb kudzu in traditional Chinese medicine, is an isoflavone compound 15 . Increasing evidence suggests that puerarin is helpful for hypertension, 16 Parkinson's disease, 17 diabetic disease 18 and tumours 19 . It was also reported to have anti‐inflammatory and antioxidant effects 20,21 .…”