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Objective <p>Globally, a significant overlap exists between females affected by HIV and HSV-2 infections, and who have an unmet need for contraception. Intravaginal rings (IVRs) have become widely accepted by women worldwide for contraception and hormone replacement therapy and provide a promising platform as a multipurpose prevention technology (MPT).</p> Methods <p>Using state-of-the-art 3D printing process known as continuous liquid interface production (CLIP™), IVRs with an internal honeycomb (HC 2.53&#xa0;mm) geometry were fabricated with a silicone-urethane resin. IVRs were loaded with a triple-drug combination of an anti-HIV drug (Dapivirine, DPV, 30&#xa0;mg), an anti-herpes drug (Pritelivir, PTV, 20&#xa0;mg) and a contraceptive hormone (Levonorgestrel, LNG, 2.0&#xa0;mg) using a solvent swelling method in acetone.</p> Results <p>IVRs elicited zero-order release kinetics following an initial burst for all three APIs when formulated individually or in combination. Release rates were above benchmark therapeutic targets for DPV and LNG (200&#xa0;µg/day DPV, 20&#xa0;µg/day LNG). A series of accelerated stability studies demonstrated the physical integrity of IVRs after 6&#xa0;months of storage at 40ºC/75%RH. DPV remained stable over 6&#xa0;months, whereas PTV and LNG exhibited significant decrease in concentration after 3&#xa0;months of storage with presence of degradation products detected by HPLC. Mouse size placebo rings (3&#xa0;mm OD) elicited 100% cell viability in relevant cell lines and were well tolerated <i>in vivo</i> in mice.</p> Conclusions <p>Collectively, these results demonstrate that this first-in-line 3D printed MPT IVR has potential to expand preventative choices for young women and girls against HIV, HSV, and unplanned pregnancy.</p> Graphical Abstract <p></p>

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Next Generation 3D Printed Multipurpose Intravaginal Ring For Sustained Co-Delivery of Antiretroviral Drugs and A Contraceptive Hormone

  • 期刊论文

  • 发表日期：

    2025年11月13日

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  • Denali K. Dahl,
  • Rima Janusziewicz,
  • Roopali Shrivastava,
  • Panita Maturavongsadit,
  • Evan Chan,
  • Stephanie A. Montgomery,
  • S. Rahima Benhabbour

摘要

Objective

Globally, a significant overlap exists between females affected by HIV and HSV-2 infections, and who have an unmet need for contraception. Intravaginal rings (IVRs) have become widely accepted by women worldwide for contraception and hormone replacement therapy and provide a promising platform as a multipurpose prevention technology (MPT).

Methods

Using state-of-the-art 3D printing process known as continuous liquid interface production (CLIP™), IVRs with an internal honeycomb (HC 2.53 mm) geometry were fabricated with a silicone-urethane resin. IVRs were loaded with a triple-drug combination of an anti-HIV drug (Dapivirine, DPV, 30 mg), an anti-herpes drug (Pritelivir, PTV, 20 mg) and a contraceptive hormone (Levonorgestrel, LNG, 2.0 mg) using a solvent swelling method in acetone.

Results

IVRs elicited zero-order release kinetics following an initial burst for all three APIs when formulated individually or in combination. Release rates were above benchmark therapeutic targets for DPV and LNG (200 µg/day DPV, 20 µg/day LNG). A series of accelerated stability studies demonstrated the physical integrity of IVRs after 6 months of storage at 40ºC/75%RH. DPV remained stable over 6 months, whereas PTV and LNG exhibited significant decrease in concentration after 3 months of storage with presence of degradation products detected by HPLC. Mouse size placebo rings (3 mm OD) elicited 100% cell viability in relevant cell lines and were well tolerated in vivo in mice.

Conclusions

Collectively, these results demonstrate that this first-in-line 3D printed MPT IVR has potential to expand preventative choices for young women and girls against HIV, HSV, and unplanned pregnancy.

Graphical Abstract