Direct-to-brain Levodopa, Curcumin Treatment May Merit Closer Look
Nanoparticles that simultaneously deliver levodopa and curcumin, a potentially neuroprotective compound, directly to the brain may be “a promising novel therapy for treating Parkinson’s disease,” researchers in Brazil and France reported.
The tiny particles created by these scientists might also help to overcome some of the drawbacks of current Parkinson’s therapies, like systemwide administration, the team noted.
Their study, “Biodegradable Nanoparticles Loaded with Levodopa and Curcumin for Treatment of Parkinson’s Disease,” was published in Molecules.
Levodopa, a mainstay treatment for Parkinson’s, effectively works by giving the body more raw material with which to make dopamine, a signaling molecule that nerve cells use to communicate. Parkinson’s is caused by the death and dysfunction of dopamine-making cells in the brain.
But patients often experience “off” periods on levodopa, times between doses when their symptoms are not controlled, and the therapy’s long-term use can result in troublesome side effects like dyskinesia (uncontrolled movements).
The researchers set out to create nanoparticles, particles too small to be seen by the eye, that can deliver levodopa to the brain. Such nanoparticles could shuttle the therapy straight to where it is needed, rather than having it absorbed via the gastrointestinal tract and shuttled to the brain, possibly reducing off periods by providing more stable dopamine levels.
The team also loaded their nanoparticles with curcumin, a compound with antioxidant and anti-inflammatory properties that has shown nerve-protecting effects in early Parkinson’s studies. Curcumin is naturally found in turmeric and is responsible for giving the spice its distinctive bright yellow-orange color. Other compounds found in turmeric have also been studied in Parkinson’s.
These nanoparticles basically consisted of levodopa and/or curcumin, wrapped in a “bubble” composed of poly ethylene oxide (PEO) and poly epsilon caprolactone (PCL). The two polymers are approved by the U.S. Food and Drug Administration for use in nanoparticle therapies.
One of the major obstacles in delivering medicines to the brain is the blood-brain barrier (BBB) that, as its name implies, regulates which substances in the blood are able to cross into the brain. The barrier works to protect the brain from infections and toxins, but it also often stops medications from getting to the central nervous system, the brain and spinal cord.
To overcome this barrier, the researchers coated the nanoparticles with glutathione (GSH), a natural antioxidant. Since glutathione is needed in the brain under healthy conditions, the BBB contains specific receptors to facilitate glutathione’s transport from the blood and into the brain.
“GSH can be used as a safe, effective, and specific ligand that can target and enhance drug delivery of NPs [nanoparticles] to the brain without toxicity,” the scientists wrote.
In a battery of lab tests, the researchers showed that their GSH-coated nanoparticles produced no signs of toxicity to cells. A necessary next step, the team noted, is to start testing the particles in animal models of Parkinson’s.
“[T]he developed biodegradable nanomicelles were blood compatible, with low cytotoxicity, and may be considered a promising novel therapy” for Parkinson’s, the researchers concluded.
“The advantages of these nanoparticles are that the treatment could be applied with lower concentrations, with the possibility of new routes of administrations, such as nasal, allied with higher treatment tolerance, due to the reduction of unwanted collateral effects,” they added.