Drug-loaded microparticles to manage Parkinson’s

IIT Delhi team used two-compartment microparticles

The microparticles can deliver the required dose in a sustained manner and reduce the pill burden and side-effects for elderly patients, says Sampa Saha (sitting)

Parkinson’s disease, which affects the central nervous system of the body currently does not have an effective cure. The dopamine (neurotransmitter chemical) deficiency caused by the disease can, however, be overcome by providing drugs which are capable of crossing the blood–brain barrier.

But most of the time only 1% of the drug (levodopa) reaches the brain after being orally taken. Using dual drugs (levodopa with carbidopa) have increased the fraction of drug reaching the brain, but low half-life has posed challenges. Also, continuous intake of levodopa has in some cases caused serious side effects such as LID (Levodopa-induced dyskinesia).

Bioavailability

With a long list of problems staring at Parkinson's disease management, now researchers from Indian Institute of Technology, Delhi have tasted success.

They have fabricated disc-shaped microparticles, merely 15 micrometres in size, made up of two compartments for carrying dual drugs without having drug–drug interactions.

The particles are made entirely of biodegradable and biocompatible polymers. “The polymers used are also FDA-approved and are currently in use as drug carriers. We tuned them according to our need. We made disc-shaped particles as they have a superior ability to attach to the intestinal lining, thereby increasing the bioavailability of the drug, crucial for oral drug delivery system” says Mr. Ashok Parthipan, first author of the paper published in

Journal of Material Sciences. Ashok completed his M.Tech degree from the Department of Materials Science and Engineering (DSME) (formerly Centre for Polymer Science and Engineering), IIT Delhi. Disc-shaped bicompartmental particles made of mucoadhesive polymers can also prolong the gastric residence time which helps in providing sustained release of dual drugs in the gastrointestinal tract.

Efficiency tested

The drug release efficiency of the microparticles were tested using different medium. Two drugs, levodopa and carbidopa (4: 1 ratio), were incorporated inside the microparticles, one inside each compartment and studied.

The researchers simulated an environment similar to our digestive system and found that major release of the drugs took place in the stomach and intestine. The drugs get absorbed in the small intestine area and then travel via blood to the blood–brain barrier. Now, carbidopa acts as a helping hand and allows levedopa to cross the crucial barrier, reach the target zone in the brain and effectively manage the dopamine deficiency.

Also, more than 80% of the drug was released within five hours in the simulated gastric fluid, which is highly beneficial from a pharmacological point of view.

“Usually a person takes multiple pills a day to efficiently manage the symptoms of Parkinson's disease. This can be replaced by just one pill as these microparticles can deliver the required dose in a sustained manner and reduce the pill burden and side-effects for elderly patients who are more likely to forget their doses and face end of dose ‘wearing-off’ symptoms”, explains Dr. Sampa Saha, Assistant Professor, DMSE, IIT, Delhi corresponding author of the paper. “We are currently carrying out animal trials and the results look promising.”