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

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.

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.

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. Similar content being viewed by others

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We would like to thank Helymar da Costa Machado, statistician from Hospital da Mulher (CAISM), University of Campinas, for assistance with the statistical analysis. We would also like to thank Kelly Mancini, a supervising nurse of the chemotherapy sector at the Perola Byington Hospital, for providing all the logistic organizations to receive our patients. Funding This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant 2014/03742-0), Brazil. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest R.A-T. has nothing to disclose. L.G. has nothing to disclose.L.G.O.B. has nothing to disclose. T.M.T. has nothing to disclose. M.O.G. has nothing to disclose. E.C.B. has nothing to disclose.R.C.M. has nothing to disclose. S.P. has nothing to disclose. Data sharing statement All data generated in the current study are available from the corresponding author upon request. IRB ethical approval statement The study protocol was approved by the Institutional Review Board of the Perola Byington Hospital (#1.937.704) and by the Ethical Committee of the Hospital of the School of Medicine of the University of Sao Paulo (#3.402.300). Trial registration: RBR-7jx2byj, URL: https://ensaiosclinicos.gov.br/rg/RBR-7jx2byj Date of registration: 01/11/22. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Avila-Tavares, R., Gibran, L., Brito, L.G.O. et al. Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles. Arch Gynecol Obstet 309, 659–667 (2024). https://doi.org/10.1007/s00404-023-07246-8 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s00404-023-07246-8