Beyond Skin-Deep: Fabrication of Nystatin-Loaded Microneedles For Enhanced and Sustained Effects against Candida albicans

Location

D.P. Culp Center Ballroom

Start Date

4-5-2024 9:00 AM

End Date

4-5-2024 11:30 AM

Poster Number

8

Name of Project's Faculty Sponsor

Ashana Puri

Faculty Sponsor's Department

Pharmaceutical Sciences

Classification of First Author

Clinical Doctoral Student

Competition Type

Non-Competitive

Type

Poster Presentation

Presentation Category

Science, Technology and Engineering

Abstract or Artist's Statement

Fungal infections, including those caused by Candida albicans, pose significant health risks, prompting the need for innovative strategies to improve treatment effectiveness. Nystatin, a polyene antifungal agent, acts by disrupting fungal cell membranes via pore formation. Although nystatin is available in various delivery formulations such as suspensions, powders, and creams, these typically require application two to three times daily. Designing a dosage form capable of sustaining nystatin delivery could offer benefits by reducing the frequency of application. Microneedles offer a minimally invasive delivery form, facilitating precise application and promoting enhanced and sustained drug absorption. This study explores the optimization of creating microneedles loaded with nystatin to contain active drug and be safely administered to treat Candida albicans infections for a sustained duration. The microneedles were made using the novel MeltPrep vacuum compression molding (VCM) that uses heat and vacuum to shape the powder inserted into the desired mold. The microneedle mold used in this study was an array of 100 needles, 8 mm x 8 mm in size, and 500 µm needle length. The strength for most nystatin formulations used in practice is 100,000 units/gram. Clove oil was included in the formulation due to the synergistic antifungal effect observed with nystatin, previously in our lab. Microneedles with 2.27% w/w nystatin, with and without clove oil (10% w/w) were fabricated using Soluplus polymer. The mixture of these ingredients was pulverized with ethanol and dried at 30°C to convert it to a powder form that could be melted using the MeltPrep VCM equipment. The powder was heated at 170°C for 15 min under a vacuum of -15 psi and cooled for 15 min to prepare the needles. The fabricated needles were observed to be sharp and pyramidal in shape as visualized under the microscope. To test the durability and effectiveness of the needles for puncturing the skin and deliver the drug contents, dermatomed pig skin was used to visualize channels formed by the needles. The microneedles were placed on the dermatomed skin and manually pressed for two minutes and then dyed with methylene blue for two minutes to observe channels formed in the skin. Dark blue channels were observed under the microscope to confirm sufficient channel formation. Further, the drug content in the needles was investigated using UV spectrophotometer (305 nm) after extraction and dilution with dimethyl sulfoxide. The drug loading in nystatin alone microneedles was found to be 1.85 ± 0.04 mg, while that of nystatin-clove oil microneedles was determined to be 1.91 ± 0.08 mg (n=3). The study, thus demonstrated the successful fabrication of nystatin-loaded microneedles using the novel VCM method for the first time. Future studies will include testing the needles efficacy against Candida albicans, in vitro and in vivo.

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Apr 5th, 9:00 AM Apr 5th, 11:30 AM

Beyond Skin-Deep: Fabrication of Nystatin-Loaded Microneedles For Enhanced and Sustained Effects against Candida albicans

D.P. Culp Center Ballroom

Fungal infections, including those caused by Candida albicans, pose significant health risks, prompting the need for innovative strategies to improve treatment effectiveness. Nystatin, a polyene antifungal agent, acts by disrupting fungal cell membranes via pore formation. Although nystatin is available in various delivery formulations such as suspensions, powders, and creams, these typically require application two to three times daily. Designing a dosage form capable of sustaining nystatin delivery could offer benefits by reducing the frequency of application. Microneedles offer a minimally invasive delivery form, facilitating precise application and promoting enhanced and sustained drug absorption. This study explores the optimization of creating microneedles loaded with nystatin to contain active drug and be safely administered to treat Candida albicans infections for a sustained duration. The microneedles were made using the novel MeltPrep vacuum compression molding (VCM) that uses heat and vacuum to shape the powder inserted into the desired mold. The microneedle mold used in this study was an array of 100 needles, 8 mm x 8 mm in size, and 500 µm needle length. The strength for most nystatin formulations used in practice is 100,000 units/gram. Clove oil was included in the formulation due to the synergistic antifungal effect observed with nystatin, previously in our lab. Microneedles with 2.27% w/w nystatin, with and without clove oil (10% w/w) were fabricated using Soluplus polymer. The mixture of these ingredients was pulverized with ethanol and dried at 30°C to convert it to a powder form that could be melted using the MeltPrep VCM equipment. The powder was heated at 170°C for 15 min under a vacuum of -15 psi and cooled for 15 min to prepare the needles. The fabricated needles were observed to be sharp and pyramidal in shape as visualized under the microscope. To test the durability and effectiveness of the needles for puncturing the skin and deliver the drug contents, dermatomed pig skin was used to visualize channels formed by the needles. The microneedles were placed on the dermatomed skin and manually pressed for two minutes and then dyed with methylene blue for two minutes to observe channels formed in the skin. Dark blue channels were observed under the microscope to confirm sufficient channel formation. Further, the drug content in the needles was investigated using UV spectrophotometer (305 nm) after extraction and dilution with dimethyl sulfoxide. The drug loading in nystatin alone microneedles was found to be 1.85 ± 0.04 mg, while that of nystatin-clove oil microneedles was determined to be 1.91 ± 0.08 mg (n=3). The study, thus demonstrated the successful fabrication of nystatin-loaded microneedles using the novel VCM method for the first time. Future studies will include testing the needles efficacy against Candida albicans, in vitro and in vivo.