Jaradat Abdolelah, Alazzo Ali, Bayan Mohammad F, Obeidat Wasfy
Department of Applied Pharmaceutical Sciences and Clinical Pharmacy, Faculty of Pharmacy, Isra University, Amman 11622, Jordan.
Department of Pharmaceutics, College of Pharmacy, University of Mosul, Mosul 41002, Iraq.
Pharmaceutics. 2025 Mar 29;17(4):438. doi: 10.3390/pharmaceutics17040438.
: Alginate nanoparticles (NPs) are commonly synthesised using either an emulsion technique that involves organic solvent use or ionotropic gelation utilising multivalent cations, e.g., Ca. However, the extensive use of organic solvents imposes detrimental effects on the ecosystem, and using multivalent cations as crosslinkers could eventually lead to the leakage of these cations, thus disrupting nanoparticle matrices. Therefore, this study aimed to overcome the limitations of these techniques by eliminating the usage of organic solvents and multivalent cations. : In this research, alginate nanoparticles were synthesised using proton gelation by microfluidic technology through protonating alginate carboxylate groups to crosslink alginate chains through H-bond formation. : The prepared acid-gelled alginate nanoparticles demonstrated an MHD circa 200 nm and a PDI of less than 0.4 at pH 0.75. Moreover, 5-FU was successfully encapsulated into acid-gelled alginate nanoparticles and displayed a high EE% of around 30%, comparable to the EE% at high alginate concentration and molecular weight (0.4 H-ALG) achieved by Ca-crosslinked alginate nanoparticles; however, 5-FU NPs had superior characteristics, i.e., a lower MHD (around 500 nm) and PDI (<0.5). The optimum formula (0.4 H-ALG) was explored at various pH values, i.e., low pH of 4.5 and high pH of 10, and alginate NPs produced by acid gelation demonstrated high stability in terms of MHD and PDI, with slight changes at different pH values, indicating stable crosslinking of alginate matrices prepared by technology compared with Ca-crosslinked alginate NPs. : In conclusion, this research has invented an ecologically friendly approach to producing acid-gelled alginate nanoparticles with superior characteristics compared with the conventional methods, and they could be harnessed as nanocarriers for therapeutics delivery (5-FU). Also, this research offers a promising approach for developing eco-friendly and biocompatible drug carriers. The produced nanoparticles have the potential to enhance drug stability, improve controlled release, and minimise toxic effects, making them suitable for pharmaceutical applications.
海藻酸钠纳米颗粒（NPs）通常采用涉及有机溶剂使用的乳液技术或利用多价阳离子（如钙）的离子交联凝胶法合成。然而，有机溶剂的大量使用对生态系统产生不利影响，并且使用多价阳离子作为交联剂最终可能导致这些阳离子泄漏，从而破坏纳米颗粒基质。因此，本研究旨在通过消除有机溶剂和多价阳离子的使用来克服这些技术的局限性。
在本研究中，通过微流控技术利用质子凝胶化合成海藻酸钠纳米颗粒，即将海藻酸钠羧酸盐基团质子化，通过氢键形成交联海藻酸链。
制备的酸凝胶化海藻酸钠纳米颗粒在pH 0.75时的平均流体动力学直径（MHD）约为200 nm，多分散指数（PDI）小于0.4。此外，5-氟尿嘧啶（5-FU）成功包封于酸凝胶化海藻酸钠纳米颗粒中，包封率（EE%）高达约30%，与钙交联海藻酸钠纳米颗粒在高海藻酸钠浓度和分子量（0.4 H-ALG）下所达到的EE%相当；然而，5-FU纳米颗粒具有更优异的特性，即较低的MHD（约500 nm）和PDI（<0.5）。在不同pH值（低pH为4.5和高pH为10）下探索了最佳配方（0.4 H-ALG），酸凝胶化制备的海藻酸钠纳米颗粒在MHD和PDI方面表现出高稳定性，在不同pH值下变化轻微，表明与钙交联海藻酸钠纳米颗粒相比，该技术制备的海藻酸基质交联稳定。
总之，本研究发明了一种生态友好的方法来制备酸凝胶化海藻酸钠纳米颗粒，与传统方法相比具有更优异的特性，并且它们可作为治疗药物递送（5-FU）的纳米载体。此外，本研究为开发生态友好且生物相容的药物载体提供了一种有前景的方法。所制备的纳米颗粒具有提高药物稳定性、改善控释和最小化毒性作用的潜力，使其适用于药物应用。
