Location
Suwanee, GA
Start Date
6-5-2025 1:00 PM
End Date
6-5-2025 4:00 PM
Description
Introduction: Levodopa, co-administered with the dopa decarboxylase inhibitor carbidopa, remains the gold standard for treating Parkinson's Disease; however, due to rapid degradation, only about 1% of orally administered levodopa crosses the blood-brain barrier. Previously, this study explored a transdermal microneedle delivery system to enhance levodopa bioavailability by bypassing gastrointestinal metabolism. Microneedles penetrate the stratum corneum, reaching the dermis—rich in blood vessels—enabling direct systemic absorption and sustained drug release.
Objective: The focus of the experiment was to first develop a levodopa-containing transdermal cream combined with microneedles to enhance skin penetration and drug absorption. Transdermal delivery systems are expected to improve patient compliance by enabling continuous administration, thereby reducing “on-off” motor fluctuations and minimizing gastrointestinal side effects commonly associated with oral medications.
Methods: In this study we used deionized (DI) water, phosphate buffered saline, and an phosphate buffered saline at a pH of 5.91 to determine the solubility of levodopa. Once we determined solubility, stabilizing the drug without using carbidopa was necessary. Multiple antioxidant or antioxidant-like chemicals were used including ethylenediaminetetraacetic acid, ascorbic acid, sodium thiosulfate anhydrous, and glutamic acid hydrochloride. These compounds were tested visually over a 30-day period and quantified using high performance liquid chromatography(HPLC).
Formulations of the hydrogels were tested using the following base polymers: polyvinyl alcohol, polyethylene glycol, carboxymethyl-cellulose sodium, and poloxamer 407 NF. Some of these polymers required crosslinkers including calcium chloride and glutaraldehyde. Additionally, the use of synthetic or natural polymers, potentially in combination with cross linkers may help maintain the benefits of the transdermal microneedle delivery, while ensuring uniform drug suspension or dissolution.
Results: From the experiment we determined a solubility of 3.3 mg/mL of levodopa in phosphate buffered saline adjusted to a pH of 6. Over 30 days, we found that the stability of levodopa was best maintained by glutamic acid hydrochloride, as quantified by HPLC, which showed a decrease of 10% over a 10 day period.
The mobile phase of the HPLC analysis followed an isocratic method consisting of 95% monopotassium phosphate and 5% methanol, using a reversed-phase C18 column for the stationary phase with dimensions of 250 mm x 4.6 and 5-micron pores. The calibration standards for this method showed a linear regression of R2 = 0.9987.
Conclusion: We were able to develop an HPLC method to quantify the concentration of levodopa and determine its stability with added glutamic acid hydrochloride over a 10-day period. Although not a curative treatment, this optimized transdermal system aims to provide more consistent dopamine replacement to improve the management of Parkinson’s disease motor symptoms.
Embargo Period
5-28-2025
Included in
Development and Characterization of Hydrogel Microneedle Patch
Suwanee, GA
Introduction: Levodopa, co-administered with the dopa decarboxylase inhibitor carbidopa, remains the gold standard for treating Parkinson's Disease; however, due to rapid degradation, only about 1% of orally administered levodopa crosses the blood-brain barrier. Previously, this study explored a transdermal microneedle delivery system to enhance levodopa bioavailability by bypassing gastrointestinal metabolism. Microneedles penetrate the stratum corneum, reaching the dermis—rich in blood vessels—enabling direct systemic absorption and sustained drug release.
Objective: The focus of the experiment was to first develop a levodopa-containing transdermal cream combined with microneedles to enhance skin penetration and drug absorption. Transdermal delivery systems are expected to improve patient compliance by enabling continuous administration, thereby reducing “on-off” motor fluctuations and minimizing gastrointestinal side effects commonly associated with oral medications.
Methods: In this study we used deionized (DI) water, phosphate buffered saline, and an phosphate buffered saline at a pH of 5.91 to determine the solubility of levodopa. Once we determined solubility, stabilizing the drug without using carbidopa was necessary. Multiple antioxidant or antioxidant-like chemicals were used including ethylenediaminetetraacetic acid, ascorbic acid, sodium thiosulfate anhydrous, and glutamic acid hydrochloride. These compounds were tested visually over a 30-day period and quantified using high performance liquid chromatography(HPLC).
Formulations of the hydrogels were tested using the following base polymers: polyvinyl alcohol, polyethylene glycol, carboxymethyl-cellulose sodium, and poloxamer 407 NF. Some of these polymers required crosslinkers including calcium chloride and glutaraldehyde. Additionally, the use of synthetic or natural polymers, potentially in combination with cross linkers may help maintain the benefits of the transdermal microneedle delivery, while ensuring uniform drug suspension or dissolution.
Results: From the experiment we determined a solubility of 3.3 mg/mL of levodopa in phosphate buffered saline adjusted to a pH of 6. Over 30 days, we found that the stability of levodopa was best maintained by glutamic acid hydrochloride, as quantified by HPLC, which showed a decrease of 10% over a 10 day period.
The mobile phase of the HPLC analysis followed an isocratic method consisting of 95% monopotassium phosphate and 5% methanol, using a reversed-phase C18 column for the stationary phase with dimensions of 250 mm x 4.6 and 5-micron pores. The calibration standards for this method showed a linear regression of R2 = 0.9987.
Conclusion: We were able to develop an HPLC method to quantify the concentration of levodopa and determine its stability with added glutamic acid hydrochloride over a 10-day period. Although not a curative treatment, this optimized transdermal system aims to provide more consistent dopamine replacement to improve the management of Parkinson’s disease motor symptoms.
Comments
Awarded "Best Cadaver/ Biomed Project" at PCOM Georgia Research Day 2025