Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles

Abstract

Objective: Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested.

Design: Prospective pilot study.

Setting: Perola Byington Hospital Reference for Women's Health.

Subjects: Eleven volunteers (aged 30-47 years, BMI 26.15 ± 6.50 kg/m²) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study.

Intervention: Three patients were treated with LDE-MTX at single intravenous 25 mg/m² dose of MTX and eight patients with two 25 mg/m² doses with 1-week interval.

Main outcome measures: Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE-MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE-MTX administration.

Results: No clinical complaints related with LDE-MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed.

Conclusion: Results support the safety and feasibility of using LDE-MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

Keywords: Bowel endometriosis; Drug delivery; Endometriosis treatment; Nanoemulsions; Solid lipid nanoparticles.