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

IF 3.6 4区 化学 Q2 CHEMISTRY, INORGANIC & NUCLEAR
Ghasem Rezanejade Bardajee, Negin Shafiei, Mahnaz Rouhi, Hossein Mahmoodian
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引用次数: 0

Abstract

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.

双响应单网络Alg-PDMAEMA纳米凝胶结肠靶向DOX的反微乳液聚合
全身毒性和肿瘤特异性差仍然是化疗面临的重大挑战,需要开发先进的给药系统。水凝胶已成为有前途的口服给药平台,提供靶向和持续释放。在这项研究中,我们通过反相微乳液聚合合成了一种簇状单网络(SN)纳米凝胶,明确设计为模拟聚合物簇的动态行为,用于结肠特异性口服给药。Alg-PDMAEMA纳米凝胶独特的簇状结构不仅增加了其表面积,而且有助于其pH和温度响应行为,密切模拟生理条件。该纳米凝胶的载药效率为87%,在pH 7.4和37°C条件下22小时的体外累积释放率为92%,而在胃条件下的释放可忽略,确保了部位特异性递送。综合表征,包括FESEM、DLS、TGA、BET、FT-IR和zeta电位分析,证实了纳米凝胶具有均匀的纳米尺度尺寸、高表面积和热稳定性。动力学和热力学分析揭示了非菲克扩散机制,表明扩散和膨胀控制释放的结合与分子簇的行为相似。细胞毒性实验进一步表明,与游离DOX相比,负载DOX的纳米凝胶使MCF-7细胞活力降低了74%,同时对正常mcf - 10a细胞保持最小的毒性。这些发现表明,簇激发的SN Alg-PDMAEMA纳米凝胶作为口服抗癌药物递送的创新平台,具有提高治疗疗效的潜力,并为簇动力学在药物控制释放中的作用提供了新的见解。
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来源期刊
Journal of Cluster Science
Journal of Cluster Science 化学-无机化学与核化学
CiteScore
6.70
自引率
0.00%
发文量
166
审稿时长
3 months
期刊介绍: The journal publishes the following types of papers: (a) original and important research; (b) authoritative comprehensive reviews or short overviews of topics of current interest; (c) brief but urgent communications on new significant research; and (d) commentaries intended to foster the exchange of innovative or provocative ideas, and to encourage dialogue, amongst researchers working in different cluster disciplines.
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