Work

An integrated drug delivery device for the localized treatment of the genitourinary syndrome of menopause

Year: 2025

Type: article

Abstract: • The novel dual-compartment device delivers hormones for targeted GSM therapy. • The design addresses dosing concerns, release control, and user acceptability. • A factorial design optimized device integrity and drug release. • A 3D bio-printed uterine-vaginal model provided realistic in vitro assessments. • The device releases hormones over 4 weeks, providing over 70 % cell viability. The Genitourinary Syndrome of Menopause (GSM) affects millions of women worldwide, with current treatment regimens associated with frequent dosing, inconsistent release profiles, and systemic adverse effects, leading to a decreased patient acceptability. Patient acceptability is pivotal in ensuring adherence and therapeutic outcomes and is defined by the European Medicines Agency as “an overall ability of the patient and caregiver to use a medicinal product as intended” with the International Conference on Harmonization Pharmaceutical Development Guideline (Q8 (R2)) further stating “in all cases, the product should be designed to meet patients’ needs and the intended product performance”. Accordingly, this study focuses on the development of a multi-unit, polymer-based, intravaginal-intrauterine platform (MUPP) for targeted and controlled hormone delivery with the aim of GSM treatment. The platform comprises of a doughnut-shaped intravaginal device (DVDS) releasing estradiol hemihydrate (E2) and an intrauterine cylindrical unit (NLPM) delivering norethindrone acetate (NETA). An experimental design was implemented to optimize DVDS formulation. The optimized device was characterized in vitro , assembled with NLPM, and evaluated for their drug release, ex vivo permeation, and cytocompatibility, using 3 T3/NIH cells and a 3D-engineered uterine-vaginal cellular model (EUVM). Results showed that the optimal DVDS and NLPM displayed cumulative releases of 5.84 ± 0.24 % (E2) 38.00 ± 1.60 % (NETA) after 4 weeks, with maximum drug flux values (peak permeation rates) of 0.18 ± 0.05 mg⋅cm −2 ⋅h −1 and 0.01 ± 0.03 mg⋅cm −2 ⋅h −1 , respectively. Moreover, cytocompatibility analyses showed an average cell viability exceeding the ISO 10993–5 minimum threshold of 70 % after 3 days, rising to above 80 % by Day 7 in both 2D and 3D models, thereby confirming the non-cytotoxic nature of the platform. In conclusion, the MUPP presents a promising and patient-friendly approach to addressing the current challenges of GSM therapy.

Source: International Journal of Pharmaceutics

DOI: 10.1016/j.ijpharm.2025.126195

Authors: Ahmed Abdelgader, Mershen Govender, Pradeep Kumar, Yahya E. Choonara

Institution: University of the Witwatersrand

Language: English

Topic: Advanced Drug Delivery Systems

Subfield: Pharmaceutical Science

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,650