Summary: Researchers have created a biodegradable, long-acting weekly injectable that steadily delivers levodopa and carbidopa, offering a potential breakthrough in Parkinson’s disease treatment. The in-situ forming gel maintains therapeutic drug levels for seven days, reducing the need for multiple daily oral doses and improving adherence and symptom control.
In laboratory tests the formulation released more than 90% of levodopa and about 81% of carbidopa over seven days, showed minimal toxicity in cell studies, and can be administered with a fine needle. This technology could also be adapted to provide long-acting therapies for other chronic conditions that require sustained drug delivery.
Key Facts:
- Steady weekly dosing: The injectable is designed to maintain consistent therapeutic drug levels for up to one week, improving symptom stability.
- Improved patient convenience: Replaces multiple daily tablets with a single weekly injection, easing treatment for elderly patients and those with swallowing difficulties.
- Versatile platform: The PLGA/Eudragit-based system can be tuned for controlled release and may be applicable to other chronic diseases requiring extended drug delivery.
Source: University of South Australia
A weekly injectable could change care for millions with Parkinson’s disease by replacing frequent oral dosing.
Researchers at the University of South Australia (UniSA) have developed an in-situ forming, biodegradable injectable that steadily releases levodopa and carbidopa — the mainstay medications for Parkinson’s disease — over seven days. The formulation is intended to simplify treatment, stabilize plasma drug concentrations, and reduce the complications associated with fluctuating drug levels.
The findings have been published in the peer-reviewed journal Drug Delivery and Translational Research. The injectable is administered subcutaneously or intramuscularly, where it forms a depot that gradually releases drugs over an entire week.
Parkinson’s disease is the second most common neurodegenerative disorder worldwide, affecting more than 8.5 million people. Current oral therapies, including levodopa combined with carbidopa, require multiple doses throughout the day because levodopa has a short half-life. This frequent dosing increases the risk of missed doses, variable blood levels, motor complications, and side effects—particularly in older patients who may have difficulty swallowing or remembering complex regimens.
Lead investigator Professor Sanjay Garg from UniSA’s Centre for Pharmaceutical Innovation emphasizes that a weekly injectable could significantly improve adherence and clinical outcomes. “Our objective was to design a formulation that simplifies treatment, stabilizes drug exposure, and improves quality of life for people living with Parkinson’s disease,” Prof. Garg says.
UniSA PhD candidate Deepa Nakmode describes the implant as an “in-situ forming” system that contains a biodegradable matrix of PLGA combined with the pH-responsive polymer Eudragit L-100. This combination enables controlled, predictable release of both levodopa and carbidopa over seven days while maintaining low viscosity for injectability.
Key laboratory outcomes included:
- Release of over 90% of levodopa and approximately 81% of carbidopa within seven days in vitro.
- More than 80% degradation of the implant matrix within seven days and no significant cytotoxicity in cell viability tests.
- Easy administration through a 22-gauge needle with low extrusion force, avoiding the need for surgical implantation and minimising injection discomfort.
The research team optimized the formulation to a blend containing 26% PLGA and 6% Eudragit L-100, which produced a favorable release profile and syringeability. In vitro data showed an initial brief burst release within the first 24 hours followed by sustained delivery, and ex vivo studies correlated closely with in vitro release profiles.
Mathematical modeling predicted pharmacokinetic parameters assuming full bioavailability, suggesting the implant could provide a stable exposure profile that reduces peaks and troughs associated with multiple daily doses. The platform’s release kinetics can be tuned to meet different therapeutic needs, ranging from several days to multiple weeks.
Beyond Parkinson’s disease, the researchers note the platform could be adapted for long-acting delivery in conditions such as diabetes, chronic infections, pain management, cancer therapies, and other neurodegenerative disorders where sustained drug exposure and improved adherence would be beneficial.
UniSA scientists are planning the next steps toward clinical evaluation and are exploring pathways for commercial development and regulatory approval. If clinical trials confirm safety and efficacy in people, a weekly levodopa–carbidopa injectable could meaningfully streamline Parkinson’s treatment and improve patients’ daily lives.
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: Image 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., published in 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 injectable systems offer improved efficacy, safety, and adherence for chronic conditions where frequent oral dosing poses challenges. This study developed an in-situ forming implant to deliver levodopa and carbidopa for up to seven days, aiming to reduce dosing frequency and stabilize therapeutic exposure.
A formulation combining poly-lactic-co-glycolic acid (PLGA 50:50) and Eudragit L-100 was optimized for controlled release and injectability. The selected composition (26% PLGA, 6% Eudragit L-100) displayed low viscosity, Newtonian flow behavior, and favorable syringeability with a maximum expulsion force of about 33 N through a 22 G needle.
In vitro release testing showed an initial release burst within 24 hours (about 34% for levodopa and 37% for carbidopa) followed by sustained release, yielding approximately 92% levodopa and 81% carbidopa release over seven days. Implant degradation studies indicated roughly 82% weight loss over the same period. Ex vivo release correlated closely with in vitro results.
Using convolution modeling to estimate in vivo performance, the projected exposure (AUC) and peak concentration (Cmax) support the potential of this in-situ forming implant as a promising long-acting delivery system for levodopa and carbidopa in Parkinson’s disease management.