Recent Advances in Non-Hormonal Drug Delivery Strategies for Endometriosis Management

Kriti Dabral Versha Gautam*
2026 · doi:10.5281/zenodo.20616822 · W7164034457
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⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-13 ⓘ

This review synthesizes evidence on nanomedicines targeting endometriosis mechanisms beyond estrogen, demonstrating preclinical efficacy with improved lesion accumulation and volume reduction, while clinical trials and GMP manufacturing remain development priorities.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-13 · read from full text ⓘ

This comprehensive review synthesizes evidence from 47 studies published between 2023 and 2026 on emerging non-hormonal nanomedicine drug delivery strategies for endometriosis, focusing on mechanisms such as angiogenesis (VEGF/HIF-1α), inflammation (COX-2, TNF-α, interleukins), extracellular matrix remodeling (MMPs), oxidative stress/iron overload, and estrogen-independent proliferative pathways (PI3K/Akt/mTOR). It reports that advanced particulate systems (including PEGylated liposomes, PLGA/chitosan nanoparticles, ROS-responsive nanocarriers, SLNs, and NLCs) and active targeting ligands (e.g., folate, LHRH, RGD/integrins, or Frizzled 7) can improve lesion accumulation several-fold and reduce lesion volumes in preclinical settings, while approaches like site-specific depot systems and devices enable sustained release from single administration. The review notes translational limitations, including limited GMP-compatible manufacturing reporting, scarcity of long-term safety data beyond six months, and insufficient evaluation of efficacy by endometriosis subtype. This paper is centrally about endometriosis — it specifically reviews non-hormonal drug delivery strategies and their efficacy across mechanistic targets and delivery platforms for endometriosis management.

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Abstract

Endometriosis is a chronic, estrogen-dependent inflammatory disorder affecting ~10% of reproductive-aged women, yet current hormonal therapies offer only symptom management, cause significant side effects, and preclude fertility. This comprehensive review synthesizes evidence from 47 studies (2023–2026) on emerging non hormonal nanomedicine strategies that target disease mechanisms independent of estrogen—including angiogenesis (VEGF/HIF 1α), inflammation (COX 2, TNF α, interleukins), matrix metalloproteinases (MMP 2/ 9), oxidative stress/iron overload (ROS, heme), and estrogen independent proliferative pathways (PI3K/Akt/mTOR). Advanced particulate delivery systems—PEGylated liposomes, PLGA and chitosan nanoparticles, ROS responsive nanocarriers, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs)—have demonstrated marked preclinical efficacy. Active targeting using folate, LHRH, integrin (RGD), or Frizzled 7 ligands improves lesion accumulation 3 to 12 fold, achieving lesion volume reductions of 59–82% while preserving ovarian function and fertility. Local and site specific systems (thermosensitive hydrogels, pH responsive gels, microneedle patches, intraperitoneal depots, and the Hyivy intravaginal device) enable sustained release with single administration; the Hyivy device reduced VAS pain scores from 7.2 to 2.5 at six months in a Phase II trial. Emerging bioinspired platforms—MSC derived exosomes, macrophage hitchhiking carriers, MMP cleavable peptide conjugates, and photothermal liposomes—have achieved lesion reductions up to 92%. Despite these advances, translational gaps remain: only 5/47 studies reported GMP compatible manufacturing, long term safety data beyond six months are scarce, and efficacy by endometriosis subtype is unexplored. However, with one FR targeted liposomal artesunate formulation qualified under the FDA ISTAND program and four ongoing clinical trials, non hormonal nanomedicines represent a paradigm shift toward fertility sparing, mechanism targeted therapies for endometriosis and related benign gynecologic disorders.
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Recent Advances in Non-Hormonal Drug Delivery Strategies for Endometriosis Management Authors/Creators Description Endometriosis is a chronic, estrogen-dependent inflammatory disorder affecting ~10% of reproductive-aged women, yet current hormonal therapies offer only symptom management, cause significant side effects, and preclude fertility. This comprehensive review synthesizes evidence from 47 studies (2023–2026) on emerging non hormonal nanomedicine strategies that target disease mechanisms independent of estrogen—including angiogenesis (VEGF/HIF 1α), inflammation (COX 2, TNF α, interleukins), matrix metalloproteinases (MMP 2/ 9), oxidative stress/iron overload (ROS, heme), and estrogen independent proliferative pathways (PI3K/Akt/mTOR). Advanced particulate delivery systems—PEGylated liposomes, PLGA and chitosan nanoparticles, ROS responsive nanocarriers, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs)—have demonstrated marked preclinical efficacy. Active targeting using folate, LHRH, integrin (RGD), or Frizzled 7 ligands improves lesion accumulation 3 to 12 fold, achieving lesion volume reductions of 59–82% while preserving ovarian function and fertility. Local and site specific systems (thermosensitive hydrogels, pH responsive gels, microneedle patches, intraperitoneal depots, and the Hyivy intravaginal device) enable sustained release with single administration; the Hyivy device reduced VAS pain scores from 7.2 to 2.5 at six months in a Phase II trial. Emerging bioinspired platforms—MSC derived exosomes, macrophage hitchhiking carriers, MMP cleavable peptide conjugates, and photothermal liposomes—have achieved lesion reductions up to 92%. Despite these advances, translational gaps remain: only 5/47 studies reported GMP compatible manufacturing, long term safety data beyond six months are scarce, and efficacy by endometriosis subtype is unexplored. However, with one FR targeted liposomal artesunate formulation qualified under the FDA ISTAND program and four ongoing clinical trials, non hormonal nanomedicines represent a paradigm shift toward fertility sparing, mechanism targeted therapies for endometriosis and related benign gynecologic disorders. Files 62-Versha Gautam.pdf Files (4.3 MB) | Name | Size | Download all | |---|---|---| | md5:1a9fa968f7125cd0b41aaf86e64ff04c | 4.3 MB | Preview Download |

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