Summary: Researchers have developed a long-acting weekly injection that delivers steady doses of levodopa and carbidopa, potentially transforming care for Parkinson’s disease. The biodegradable injectable maintains consistent drug levels, reducing the need for multiple daily pills and improving patient adherence.
In lab tests, the gel released over 90% of the levodopa and 81% of the carbidopa within seven days, with minimal toxicity and easy administration. This innovation could also pave the way for long-acting therapies for other chronic diseases.
Key Facts:
- Steady Dosing: The injectable maintains consistent therapeutic levels over a week, improving symptom control.
- Easier for Patients: Reduces the burden of taking multiple daily pills, particularly for elderly patients with swallowing difficulties.
- Broad Potential: The technology could be adapted for other chronic conditions requiring long-term treatment.
Source: University of South Australia
A new weekly injectable drug could transform the lives of more than eight million people living with Parkinson’s disease, potentially replacing the need for multiple daily tablets.
Scientists from the University of South Australia (UniSA) have developed a long-acting injectable formulation that delivers a steady dose of levodopa and carbidopa – two key medications for Parkinson’s – over an entire week.
Their findings have been reported in the journal Drug Delivery and Translational Research.
The biodegradable formulation is injected under the skin or into muscle tissue, where it gradually releases the medication over seven days.
Parkinson’s disease is the second most common neurological disorder, affecting more than 8.5 million people worldwide.
Currently there is no cure and the symptoms – tremors, rigidity and slow movement – are managed with oral medications that must be taken several times a day.
The frequent dosing is a burden, especially for elderly patients or those with swallowing difficulties, leading to inconsistent medication levels, more side effects, and reduced effectiveness.
Lead researcher Professor Sanjay Garg, from UniSA’s Centre for Pharmaceutical Innovation, says the newly developed injectable could significantly improve treatment outcomes and patient adherence.
“Our goal was to create a formulation that simplifies treatment, improves patient compliance, and maintains consistent therapeutic levels of medication. This weekly injection could be a game-changer for Parkinson’s care,” Prof Garg says.
“Levodopa is the gold-standard therapy for Parkinson’s, but its short life span means it must be taken several times a day.”
UniSA PhD student Deepa Nakmode says the in-situ implant is designed to release both levodopa and carbidopa steadily over one week, maintaining consistent plasma levels and reducing the risks associated with fluctuating drug concentrations.
“After years of focused research, it’s incredibly rewarding to see our innovation in long-acting injectables for Parkinson’s disease reach this stage. Our invention has now been filed for an Australian patent,” Nakmode says.
The injectable gel combines an FDA-approved biodegradable polymer PLGA with Eudragit L-100, a pH-sensitive polymer, to achieve a controlled and sustained drug release.
Extensive lab tests confirmed the system’s effectiveness and safety:
- More than 90% of the levodopa dose and more than 81% of the carbidopa dose was released over seven days.
- The implant degraded by over 80% within a week and showed no significant toxicity in cell viability tests.
- The formulation can be easily administered through a fine 22-gauge needle, minimising discomfort and eliminating the need for surgical implant.
“The implications of this research are profound,” Prof Garg says.
“By reducing the frequency of dosing from multiple times a day to a weekly injection is a major step forward in Parkinson’s therapy. We’re not just improving how the drug is delivered; we’re improving patients’ lives.”
Prof Garg says the technology could also be adapted for other chronic conditions such as cancer, diabetes, neurodegenerative disorders, pain management, and chronic infections that require long-term drug delivery.
The system can be tuned to release drugs over a period ranging from a few days to several weeks depending on therapeutic needs.
UniSA scientists hope to start clinical trials in the near future and are exploring commercialisation opportunities.
About this Parkinson’s disease and neuropharmacology research news
Author: Candy Gibson
Source: University of South Australia
Contact: Candy Gibson – University of South Australia
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Development of an in-situ forming implant system for levodopa and carbidopa for the treatment of Parkinson’s disease” by Sanjay Garg et al. Drug Delivery and Translational Research
Abstract
Development of an in-situ forming implant system for levodopa and carbidopa for the treatment of Parkinson’s disease
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.
