Formulation and characterization of pressure-assisted microsyringe 3D-printed scaffolds for controlled intravaginal antibiotic release

Anthony J Kyser; Mohamed Y Mahmoud; Sydney E Herold; Warren G Lewis; Amanda L Lewis; Jill M Steinbach-Rankins; Hermann B Frieboes

doi:10.1016/j.ijpharm.2023.123054

Formulation and characterization of pressure-assisted microsyringe 3D-printed scaffolds for controlled intravaginal antibiotic release

Int J Pharm. 2023 Jun 25:641:123054. doi: 10.1016/j.ijpharm.2023.123054. Epub 2023 May 18.

Authors

Anthony J Kyser¹, Mohamed Y Mahmoud², Sydney E Herold³, Warren G Lewis⁴, Amanda L Lewis⁵, Jill M Steinbach-Rankins⁶, Hermann B Frieboes⁷

Affiliations

¹ Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY 40202, USA. Electronic address: ajkyse01@louisville.edu.
² Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY 40202, USA; Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Egypt. Electronic address: myabde01@louisville.edu.
³ Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY 40202, USA. Electronic address: sydney.herold@louisville.edu.
⁴ Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, La Jolla, CA 92093, USA; Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: wglewis@ucsd.edu.
⁵ Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Diego, La Jolla, CA 92093, USA; Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: a1lewis@ucsd.edu.
⁶ Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY 40202, USA; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA; Center for Predictive Medicine, University of Louisville, Louisville, KY 40202, USA; Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40202, USA. Electronic address: jmstei01@louisville.edu.
⁷ Department of Bioengineering, University of Louisville Speed School of Engineering, Louisville, KY 40202, USA; Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA; Center for Predictive Medicine, University of Louisville, Louisville, KY 40202, USA; UofL Health - Brown Cancer Center, University of Louisville, KY 40202, USA. Electronic address: hbfrie01@louisville.edu.

PMID: 37207856
PMCID: PMC10330500 (available on 2024-06-25)
DOI: 10.1016/j.ijpharm.2023.123054

Abstract

Bacterial vaginosis (BV) is a highly recurrent vaginal condition linked with many health complications. Topical antibiotic treatments for BV are challenged with drug solubility in vaginal fluid, lack of convenience and user adherence to daily treatment protocols, among other factors. 3D-printed scaffolds can provide sustained antibiotic delivery to the female reproductive tract (FRT). Silicone vehicles have been shown to provide structural stability, flexibility, and biocompatibility, with favorable drug release kinetics. This study formulates and characterizes novel metronidazole-containing 3D-printed silicone scaffolds for eventual application to the FRT. Scaffolds were evaluated for degradation, swelling, compression, and metronidazole release in simulated vaginal fluid (SVF). Scaffolds retained high structural integrity and sustained release. Minimal mass loss (<6%) and swelling (<2%) were observed after 14 days in SVF, relative to initial post-cure measurements. Scaffolds cured for 24 hr (50 °C) demonstrated elastic behavior under 20% compression and 4.0 N load. Scaffolds cured for 4 hr (50 °C), followed by 72 hr (4 °C), demonstrated the highest, sustained, metronidazole release (4.0 and 27.0 µg/mg) after 24 hr and 14 days, respectively. Based upon daily release profiles, it was observed that the 24 hr timepoint had the greatest metronidazole release of 4.08 μg/mg for scaffolds cured at 4 hr at 50 °C followed by 72 hr at 4 °C. For all curing conditions, release of metronidazole after 1 and 7 days showed > 4.0-log reduction in Gardnerella concentration. Negligible cytotoxicity was observed in treated keratinocytes comparable to untreated cells, This study shows that pressure-assisted microsyringe 3D-printed silicone scaffolds may provide a versatile vehicle for sustained metronidazole delivery to the FRT.

Keywords: 3D-printing; Bacterial vaginosis; Drug delivery; Gardnerella; Metronidazole; Sustained release; Vaginal microbiome.

MeSH terms

Administration, Intravaginal
Anti-Bacterial Agents*
Female
Humans
Metronidazole
Printing, Three-Dimensional
Vaginosis, Bacterial* / drug therapy

Substances

Anti-Bacterial Agents
Metronidazole

Grants and funding

R01 AI168475/AI/NIAID NIH HHS/United States