In vitro evaluation of microfluidic WS6-loaded Eudragit nanoparticles for improving insulin-producing cell differentiation
Duaa Abuarqoub, Marwa Mohammad, Rand Albarghouthi, Mohammad Abuoun, Mohammad Alnatour, Fuad Alhawarat, Abdolelah Jaradat
Abstract
This study explores a stem-cell–based approach for diabetes treatment by enhancing the viability and functionality of insulin-producing cells (IPCs) derived from stem cells of the apical papilla (SCAP). Although SCAP can differentiate into IPCs, limited cell survival remains a challenge. To address this, the proliferation enhancer WS6 was incorporated into Eudragit RS100 nanoparticles (NPs) using microfluidics. The WS6-loaded NPs were characterized for size, charge, PDI, morphology, stability, and drug loading.
Introduction
Diabetes Mellitus (DM) is a global public health burden; approximately 585 million people are living with diabetes according to the last report of the International Diabetes Atlas (IDF) in 2025 [1]. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs [2]. Promoting islet β‐cell regeneration and restoring endogenous insulin secretion may present an ideal approach to curing diabetes [3–5]. Yet, efforts to engineer islet-like cells or insulin-producing cells from different types of stem cells have offered an appealing alternative to islet transplants.
Materials and method
2.1. Preparation of WS6-loaded nanoparticles (WS6-NPs)
WS6-loaded NPs were synthesized using a microfluidic system (Dolomite Microfluidics, UK). As previously described [21]. The microfluidic chip was a quartz-based X-junction design with dimensions of 22.5 × 15 × 4 mm, and the channel width was 190 µm. Eudragit-RS dissolved in acetone (1 mg/ml) and loaded with WS6 (284.3 µg), then introduced into the central phase at 0.25 ml/min. Simultaneously, an acetate buffer (pH 5) was infused through the lateral phase at 0.5 ml/min, maintaining dual-phase flow for 2 min.
Results
3.1. Characterization of WS6-loaded NPs
3.1.1. Stability results: DLS and content measurement.
WS6-NPs stability was evaluated over 72 hrs, and results showed that particle size distribution was stable throughout the study, with mean diameters of 149.9 ± 27.7 nm, 157.3 ± 7.4 nm, and 141.0 ± 22.0 nm at 24, 48, and 72hrs, respectively. No significant aggregation was observed compared to freshly prepared WS6-NPs 149.3 ± 15.2 nm.
Discussion
Recent progress in stem cell therapy has enabled the differentiation of mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs), yet the limited viability and short lifespan of the differentiated cells continue to restrict their therapeutic potential [33].
Conclusion
WS6 acts as a potent small-molecule stimulator of β-cell proliferation and differentiation, and its microfluidics NPs formulation represents a promising strategy to enhance the survival, functionality, and therapeutic efficacy of stem-cell–derived IPCs, advancing the goal of a cell-based alternative to insulin injection for diabetes management using NPs delivery systems for enhancing the survival rate.
Acknowledgments
Informed consent: All participants signed an informed consent before they participated in the study.
Citation: Abuarqoub D, Mohammad M, Albarghouthi R, Abuoun M, Alnatour M, Alhawarat F, et al. (2026) In vitro evaluation of microfluidic WS6-loaded Eudragit nanoparticles for improving insulin-producing cell differentiation. PLoS One 21(8): e0354587. https://doi.org/10.1371/journal.pone.0354587
Editor: Gianpaolo Papaccio, Università degli Studi della Campania, ITALY
Received: March 26, 2026; Accepted: July 7, 2026; Published: August 4, 2026
Copyright: © 2026 Abuarqoub et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript.
Funding: This research was financially supported by the scientific research funding provided by the Ministry of Higher Education (grant #MPH/1/59/2023) and the Deanship of Scientific Research at the University of Petra (22/4/2023).
Competing interests: The authors have declared that no competing interests exist.
