Microneedle Patch for Sustained Delivery of Hydroxyurea and L-Glutamine for Sickle Cell Treatment
Authors: Bhoorasingh Michaela E. , Jeong Sangmoo 
Published: December 2024

Sickle cell anemia (SCA) is a genetic blood disorder in which the red blood cells have a sickled shape due to a mutation in hemoglobin. The sickle-shaped red blood cells can cause blockages in blood vessels, leading to various complications, such as vaso-occlusive crises (VOCs), acute chest syndrome, stroke, and organ damage. In 2023 the FDA approved two genetic therapies to cure SCA. However, these therapies are expensive and as a result, patients are more likely to choose treatments that manage their SCA and reduce VOCs. Currently, there are only two FDA-approved management treatments for SCA: hydroxyurea and L-glutamine. Unfortunately, these treatments require daily or twice daily dosages and have severe side effects, a major challenge for patients to comply with daily administration. To address this problem, I propose a novel approach: a microneedle patch for the sustained release of these drugs over a week. I expect that this innovative therapeutic strategy will directly improve patient compliance and quality of life.

Microneedle (MN) patches are a novel and non-invasive method of transdermal drug delivery. They consist of a patch backing and MN tips that are inserted into the skin. Passive transdermal drug delivery is limited by the outermost layer of the skin, the stratum corneum. MN patches overcome this limitation by disrupting the stratum corneum and reaching the lower layers of the epidermis for drug administration. MN patches have been shown to significantly reduce severe side effects, such as ulcers, nausea and muscle pain, by providing consistent drug release and bypassing hepatic metabolism. Our MN patch is made of gelatin methacrylol (GelMA) and PLGA, both of which are biocompatible and biodegradable. This allows the patch to degrade over a period of one week, with negligible adverse reaction and discomfort when applied the skin. The MN patch is designed to meet the FDA recommended dose of hydroxyurea (10 to 40 mg/kg/day) and L-glutamine (5 to 15 g/dose).

The synthesis of the MN patch is done by first combining two solutions: (1) GelMA and PLGA (40:60 ratio) in 90% dioxane solution and (2) hydroxyurea and L-glutamine in 5% water solution. The mixture is added to a PDMS mold in a layer-by-layer method, with centrifugation between layers to remove air bubbles. After 5-minute UV curing, the patch is left to dry overnight and ready for use. Our device has achieved the required mechanical force of 0.3N to penetrate the stratum corneum. The MN tips have a height of 600 µm to remain in the viable epidermis and avoid contact with nerves. We have also demonstrated that the MN design has a linear release profile when loaded with L-glutamine. Moreover, we have developed a mass spectrometry-based technology to quantify hydroxyurea concentration in solution. This method enables sensitive and quantitative analysis of the release profile of hydroxyurea from the MN patch in both in vitro and in vivo settings. Our optimized device will be tested on the Townes mouse models, and its therapeutic efficacy will be presented at the 2024 ASH Annual Meeting.