Novel drug delivery methods for improving efficacy of endometriosis treatments

ABSTRACT

Introduction

Pharmacotherapy has a key role in the management of endometriosis. However, a significant proportion of patients gains only intermittent or limited benefits. In this regard, alternative and novel drug delivery methods are of paramount importance to improve efficacy and compliance of available treatments and develop alternative medical approaches.

Areas covered

This review aims to provide the reader with a complete overview of available evidence about alternative and novel drug delivery methods for endometriosis pharmacotherapy and highlight new research lines.

Expert opinion

Progestins and estroprogestins, which represent the first-line therapy, are already available in different formulations, being employed for contraception. Nevertheless, evidence on their adoption is still limited for some drug delivery methods, such as vaginal rings, patches, and subcutaneous implants. Further research is needed to define better their clinical utility in patients with endometriosis. Nanotechnologies have been investigated as novel drug delivery methods able to target the drug at the disease level. However, data are very limited and preliminary, and further research is needed to consider a possible clinical application in endometriosis.

KEYWORDS:

• Endometriosis
• drug delivery
• adverse effects
• nanotechnology
• vaginal ring
• intrauterine systems
• depot preparation

Article highlights

• Pharmacotherapy has a key role in treating endometriosis, but a significant proportion of patients gains only intermittent or limited benefits. Adopting alternative drug delivery methods could improve compliance, increase efficacy, and develop new therapeutic approaches.

• Progestins and estroprogestins therapy for endometriosis can take advantage of available formulations adopted for contraception, allowing personalizing the treatment, improving compliance, reducing adverse effects, and potentially increasing efficacy.

• In randomized controlled trials (RCTs) on endometriosis patients, levonorgestrel intrauterine systems (LNG-IUSs) were associated with improved pain and satisfaction compared to observation after surgery. LNG-IUSs compared to other therapies did not improve symptoms, but may improve satisfaction and compliance, although uncertainties about their efficacy on endometriomas have questioned their use.

• Multiple RCTs studied depot medroxyprogesterone acetate (DMPA) as a treatment for endometriosis. DMPA reduced pain similarly to GnRH analogs, but improved quality of life and reduced bone loss and hypoestrogenic symptoms. Irregular bleeding is the main adverse effect.

• Other progestin and estroprogestins delivery methods available for contraception, such as vaginal rings, patches, and subcutaneous implants, have been investigated to only a limited extent in patients with endometriosis. However, the vaginal ring has been investigated as a novel drug delivery method for danazol and aromatase inhibitors.

• Nanotechnologies are possible novel drug delivery methods preliminarily investigated in endometriosis animal models. They consist of bioconjugates delivering anti-inflammatory, antioxidant, anti-angiogenetic, and immunomodulating molecules at the disease level. However, data are very limited and preliminary at an early-stage proof-on-concept level. Further research is needed to evaluate a possible clinical application in endometriosis. Mouse models are not able to predict clinical efficacy.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.