Practical And Effective Solution: Weekly Injection Can Change Routine For Parkinson's Patients

Parkinson's disease affects body movements because the brain stops producing dopamine, a substance important for motor control. The main treatment is levodopa, but it needs to be taken several times a day, which can be difficult for many patients, especially the elderly. Therefore, scientists are developing a new way to administer the medication: a type of injection that forms a small implant inside the body and releases the medication gradually over a week. This new method could facilitate treatment, reduce side effects, and improve the quality of life for those with Parkinson's.

Parkinson's disease is a chronic and progressive brain condition that impairs body movements. This occurs because the neurons that produce dopamine, a chemical messenger essential for motor control, gradually die. It is the second most common neurological disease worldwide, affecting approximately 8.5 million people.

Although there is still no cure, current treatment focuses on symptom relief. The main medication used is levodopa, which replenishes dopamine in the brain and improves movement. To work best, it's combined with another substance called carbidopa, which prevents levodopa from being broken down outside the brain before it takes effect.

Levodopa acts quickly in the body, but because its effects are short-lived, patients need to take it several times a day. This can be a problem, especially for older people or those with difficulty swallowing pills.

Furthermore, these repeated doses cause fluctuations in blood drug levels, which can lead to side effects and unstable symptoms. Therefore, researchers have been looking for ways to make treatment more consistent and less laborious.

One such alternative is long-acting injectables, which release the drug slowly and continuously into the body over several days. They help maintain more stable drug levels, reducing the number of doses and side effects.

Among the techniques being studied is the use of implants that form inside the body, called in situ systems. These are liquid substances applied with a small needle, which transform into a type of gel or solid implant when they come into contact with body fluids, gradually releasing the drug.

In this study, scientists developed such a system to administer levodopa and carbidopa in a controlled manner for up to a week. They used two types of biodegradable polymers: PLGA, which is already widely used in extended-release medications, and Eudragit L-100, which helps adjust the timing and form of drug release.

This image shows how a new type of weekly injection to treat Parkinson's disease was developed and tested. In part A (left), we see the preparation process: researchers mixed two polymers (PLGA and Eudragit) with two medications (levodopa and carbidopa), which are the most commonly used to treat the symptoms of the disease. This mixture was heated and then cooled, forming a liquid formulation ready for injection. In part B (right), the tests performed with this formulation are shown. They evaluated the drug's release over time in the laboratory (in vitro), the liquid's thickness (viscosity), its safety for cells (cell viability test), and made predictions about how it would work in the human body. The goal is for this injection to release the drug in a controlled manner for up to a week, avoiding the need for patients to take multiple pills per day, which would greatly facilitate Parkinson's treatment.

The chosen formula showed good results: it released almost all of the medication over seven days, maintained good viscosity (facilitating syringe application), and proved to be safe for cells.

Tests showed that the new formulation releases 34% of the levodopa and 37% of the carbidopa in the first 24 hours, and approximately 90% after a week. Furthermore, the implant practically dissolved in the body at the end of this period.

Simulations conducted in a laboratory and in an environment similar to the human body indicated that the drug levels in the blood would be sufficient for the expected therapeutic effect. This suggests that this new system may be a promising and more practical way to treat Parkinson's disease in the future, offering patients greater comfort and regularity.

Scanning electron microscopy (SEM) of the implant collected from samples. The images show implant samples collected on Day 1, Day 3, and Day 9. Notable differences were observed in the surface porosity of the samples collected at different time points. The Day 1 sample presented a compact structure on the surface as well as in the cross-section. Therefore, drug release in the first 8 hours may have occurred from the implant surface. Over time, a porous structure formed. On Day 3, pores began to form on the implant surface, with a less compact structure in the cross-section. Furthermore, swelling of the internal structure was observed on Day 3, which may be a characteristic of increased drug release from the implant via diffusion toward the release medium. On Day 7, up to 90% of the drug was released; the surface became very porous, with erosion of the polymer structure highlighted in the red circle.

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Development of an in-situ forming implant system for levodopa and carbidopa for the treatment of parkinson’s disease. 

Deepa D. Nakmode, Sadikalmahdi Abdella, Yunmei Song, and Sanjay Garg 

Drug Deliv. and Transl. Res. 07 June 2025

https://doi.org/10.1007/s13346-025-01892-y

Abstract: 

Long-acting injectables have gained attraction as a system for treating chronic conditions due to their increased efficacy, safety, and patient compliance. Currently, patients with Parkinsons need to administer oral medications multiple times a day which imposes the significant risk of non-compliance. This study aimed to design an in-situ implant-forming system for controlled delivery of levodopa and carbidopa for up to 1 week which will reduce the need for multiple dosing. The combination of poly-lactic-co-glycolic acid (PLGA 50:50) and Eudragit L-100 was used to prepare the implants and the formulation was optimized to achieve a controlled release over 7 days. The optimized formulation containing 26% PLGA and 6% Eudragit L 100 displayed a favorable release profile and injectability with low viscosity. The optimized formulation in vitro release study revealed an initial burst of 34.17% and 37.16% for levodopa and carbidopa in the first 24 h and about 92% and 81% release within 7 days. A good correlation was observed between the in-vitro drug release data and ex-vivo drug release with a correlation coefficient of 0.91 for levodopa and 0.90 for carbidopa. Viscosity analysis showed the Newtonian behavior of the formulation. Syringeability analysis of the formulation showed that the maximum force required for expelling the formulation was 32.98 ± 0.72 N using a 22 G needle. The in-vitro degradation studies revealed 81.89% weight loss of implant in 7 days. The prepared formulation was assessed for in-vivo performance using a convolution modeling technique using a convolve function in R software. The predicted AUC 0-∞ h for the in-situ forming implant was 26505.5 ng/ml with Cmax, 399.3 ng/ml, and Tmax 24 h assuming 100% bioavailability. The results justify that the prepared in-situ implant forming system can be a promising system for the delivery of levodopa and carbidopa for Parkinson’s patients.