Multifunctional Chitosan-Coated Alginate Microspheres Loaded with Spirulina, Hydroxyapatite, and Metronidazole for Sustainable Periodontitis Treatment

IF 5 3区工程技术 Q2 ENGINEERING, ENVIRONMENTAL

Journal of Polymers and the Environment Pub Date : 2025-05-29 DOI:10.1007/s10924-025-03607-3

Madeeha Arif, Aqsa Afzaal, Farhat Rafiq, Maleeha Nayyer, Muhammad Saleem, Mazhar Amjad Gilani, Muhammad Kaleem, Sobia Tabassum

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Abstract

Chitosan-coated alginate microspheres (M0, M1, M2.5, and M5) loaded with spirulina extract, hydroxyapatite, and metronidazole were developed for periodontitis treatment. Fabricated via ionotropic gelation, these formulations were characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. Their swelling kinetics and biodegradation rate indicated suitability for periodontitis treatment. The M5 formulation demonstrated superior drug loading (73.3 mg/g) and sustained release profiles, achieving 99.67% cumulative metronidazole release over 72 h. Korsmeyer-Peppas modeling revealed non-Fickian release mechanisms (n = 0.48–0.66) for all drug-loaded samples (M1, M2.5, M5), governed by diffusion, polymer swelling, and erosion. All formulations exhibited excellent antibacterial activity against Staphylococcus aureus and Escherichia coli. The microspheres showed 50–60% scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, demonstrating their potential to suppress intracellular reactive oxygen species (ROS) production. They also displayed excellent hemocompatibility (< 3% hemolysis) and enhanced NIH3T3 fibroblast viability. In wound healing assays, the M5 formulation promoted 80% wound closure within 24 h, significantly outperforming both control and M0 samples. At the molecular level, prepared microspheres upregulated vascular endothelial growth factor (VEGF) expression by up to 6-fold while suppressing tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) by 60–70%, demonstrating combined angiogenic and anti-inflammatory effects. In conclusion, the M5 formulation emerged as particularly promising, combining optimal drug loading, sustained release, and multifunctional therapeutic effects. Thisstudy represents a significant advancement in localized periodontitis therapy, addressing infection control while promoting tissue regeneration through their unique composition of spirulina, hydroxyapatite, and metronidazole.

Graphical Abstract

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含有螺旋藻、羟基磷灰石和甲硝唑的多功能壳聚糖包被海藻酸盐微球用于牙周炎的可持续治疗

壳聚糖包被海藻酸微球（M0, M1, M2.5和M5）装载螺旋藻提取物，羟基磷灰石和甲硝唑用于牙周炎治疗。这些配方通过离子化胶凝制备，用扫描电子显微镜、傅里叶变换红外光谱和x射线衍射对其进行了表征。它们的肿胀动力学和生物降解率表明它们适合治疗牙周炎。M5具有优异的载药量（73.3 mg/g）和缓释特性，72小时内甲硝唑的累积释放量达到99.67%。korsmemeyer - peppas模型显示，所有载药样品（M1、M2.5、M5）的非菲克释放机制（n = 0.48-0.66）受扩散、聚合物膨胀和侵蚀控制。所有制剂均对金黄色葡萄球菌和大肠杆菌具有良好的抑菌活性。该微球在2,2-二苯基-1-吡啶肼（DPPH）检测中显示出50-60%的清除活性，表明其具有抑制细胞内活性氧（ROS）产生的潜力。它们还表现出优异的血液相容性（溶血3%）和增强的NIH3T3成纤维细胞活力。在伤口愈合试验中，M5配方在24小时内促进了80%的伤口愈合，显著优于对照组和M0样品。在分子水平上，制备的微球上调血管内皮生长因子（VEGF）的表达高达6倍，同时抑制肿瘤坏死因子-α (TNF-α)和白细胞介素-1β (IL-1β) 60-70%，显示出血管生成和抗炎的综合作用。综上所述，M5的配方结合了最佳的药物负荷、缓释和多功能治疗效果，具有特别的前景。本研究代表了局部牙周炎治疗的重大进展，通过螺旋藻、羟基磷灰石和甲硝唑的独特组成，在控制感染的同时促进组织再生。图形抽象

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来源期刊

Journal of Polymers and the Environment 工程技术-高分子科学

CiteScore

9.50

自引率

7.50%

发文量

297

审稿时长

9 months

期刊介绍： The Journal of Polymers and the Environment fills the need for an international forum in this diverse and rapidly expanding field. The journal serves a crucial role for the publication of information from a wide range of disciplines and is a central outlet for the publication of high-quality peer-reviewed original papers, review articles and short communications. The journal is intentionally interdisciplinary in regard to contributions and covers the following subjects - polymers, environmentally degradable polymers, and degradation pathways: biological, photochemical, oxidative and hydrolytic; new environmental materials: derived by chemical and biosynthetic routes; environmental blends and composites; developments in processing and reactive processing of environmental polymers; characterization of environmental materials: mechanical, physical, thermal, rheological, morphological, and others; recyclable polymers and plastics recycling environmental testing: in-laboratory simulations, outdoor exposures, and standardization of methodologies; environmental fate: end products and intermediates of biodegradation; microbiology and enzymology of polymer biodegradation; solid-waste management and public legislation specific to environmental polymers; and other related topics.