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<p>Systemic toxicity and poor tumor specificity remain significant challenges in chemotherapy, necessitating the development of advanced drug delivery systems. Hydrogels have emerged as promising platforms for oral drug delivery, offering targeted and sustained release. In this study, we synthesized a cluster-shaped single-network (SN) nanogel via inverse miniemulsion polymerization, explicitly designed to mimic the dynamic behavior of polymer clusters, for colon-specific oral administration. The unique cluster-like organization of the Alg-PDMAEMA nanogel not only increases its surface area but also contributes to its pH- and temperature-responsive behavior, closely emulating physiological conditions. The nanogel achieved a drug loading efficiency of 87% and demonstrated a cumulative in vitro release of 92% over 22&#xa0;h at pH 7.4 and 37&#xa0;°C, while negligible release under gastric conditions ensured site-specific delivery. Comprehensive characterization, including FESEM, DLS, TGA, BET, FT-IR, and zeta potential analyses, confirmed the nanogel’s uniform nanoscale size, high surface area, and thermal stability. Kinetic and thermodynamic analyses revealed a non-Fickian diffusion mechanism, indicative of a combination of diffusion- and swelling-controlled release that parallels the behavior of molecular clusters. Cytotoxicity assays further demonstrated that DOX-loaded nanogels reduced MCF-7 cell viability by 74% compared to free DOX while maintaining minimal toxicity toward normal MCF-10&#xa0;A cells. These findings suggested the potential of cluster-inspired SN Alg-PDMAEMA nanogels as an innovative platform for oral anticancer drug delivery, enhancing therapeutic efficacy and offering new insights into the role of cluster dynamics in controlled drug release.</p>

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Inverse Miniemulsion Polymerization of Dual-Responsive Single-Network Alg-PDMAEMA Nanogels Colon-Targeted DOX Delivery

  • 期刊论文

  • 发表日期：

    2025年7月11日

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  • Ghasem Rezanejade Bardajee,
  • Negin Shafiei,
  • Mahnaz Rouhi,
  • Hossein Mahmoodian

摘要

Systemic toxicity and poor tumor specificity remain significant challenges in chemotherapy, necessitating the development of advanced drug delivery systems. Hydrogels have emerged as promising platforms for oral drug delivery, offering targeted and sustained release. In this study, we synthesized a cluster-shaped single-network (SN) nanogel via inverse miniemulsion polymerization, explicitly designed to mimic the dynamic behavior of polymer clusters, for colon-specific oral administration. The unique cluster-like organization of the Alg-PDMAEMA nanogel not only increases its surface area but also contributes to its pH- and temperature-responsive behavior, closely emulating physiological conditions. The nanogel achieved a drug loading efficiency of 87% and demonstrated a cumulative in vitro release of 92% over 22 h at pH 7.4 and 37 °C, while negligible release under gastric conditions ensured site-specific delivery. Comprehensive characterization, including FESEM, DLS, TGA, BET, FT-IR, and zeta potential analyses, confirmed the nanogel’s uniform nanoscale size, high surface area, and thermal stability. Kinetic and thermodynamic analyses revealed a non-Fickian diffusion mechanism, indicative of a combination of diffusion- and swelling-controlled release that parallels the behavior of molecular clusters. Cytotoxicity assays further demonstrated that DOX-loaded nanogels reduced MCF-7 cell viability by 74% compared to free DOX while maintaining minimal toxicity toward normal MCF-10 A cells. These findings suggested the potential of cluster-inspired SN Alg-PDMAEMA nanogels as an innovative platform for oral anticancer drug delivery, enhancing therapeutic efficacy and offering new insights into the role of cluster dynamics in controlled drug release.