Sustained progesterone supplementation with state-of-the-art 3D printed intravaginal ring for the treatment of...

Infertility is a growing global unmet need. Progesterone (PRO) is a vital hormone in the treatment of infertility however supplementation options remain limited. We propose the use of 3D printed intravaginal rings (IVRs) to enable sustained delivery of PRO over 28 days. An iterative design process was utilized to first explore the in vitro release properties of preliminary IVR designs in simulated vaginal fluid. A solid placebo IVR was carried forward in vivo using an ovine model to investigate the local tolerability and safety of the 3D printed polymer. A solid PRO-loaded IVR was investigated in vivo to assess safety and pharmacokinetics over 35 days. Initial IVR designs demonstrated the ability to release PRO from 3D printed IVRs for >100 days in vitro, with release rate and duration driven by PRO loading amount and IVR design. Solid IVRs were well tolerated in sheep but elicited levels of plasma PRO below our target therapeutic concentrations. Collectively, these data were iteratively used to develop ANLO101, an IVR with similar loading capacity but with greater surface area and therefore an increased PRO release rate and was developed by implementing design that increased surface area while maintaining volume. ANLO101 was investigated in vitro and in vivo for PRO release. ANLO101 reached our target PRO release in vitro (≥11 mg/day) and target plasma concentrations (6-9 ng/mL). We report for the first time sustained progesterone delivery of >28 days with ANLO101, an IVR that may be a self-administered product for infertility treatment.