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<p>Alzheimer’s disease (AD) therapies remain limited by poor blood–brain barrier (BBB) penetration and modest cognitive recovery. This study aimed to develop and evaluate transferrin-conjugated S-adenosylmethionine-loaded citric acid-stabilized superparamagnetic iron oxide nanoparticles (Tf-SAMe-CA-SPIONs) as a targeted nanoplatform for brain delivery. SPIONs were synthesised by co-precipitation and optimised using a design of experiments approach. The formulation was characterised for physicochemical, magnetic, and structural attributes, and its BBB permeability and neuroprotective efficacy were assessed using in vitro and zebrafish AD models. The optimised SPIONs displayed hydrodynamic diameters of 58–71&#xa0;nm (PDI &lt; 0.33). Following citric acid stabilisation, the particle size increased to 111.3&#xa0;nm (PDI 0.347, zeta potential –20.08&#xa0;mV), while transferrin–SAMe conjugation further enlarged the particles to around 196.4&#xa0;nm with a zeta potential of –28.28&#xa0;mV. XRD confirmed the magnetite spinel crystalline structure, and VSM analysis verified their superparamagnetic behaviour with a saturation magnetisation (Ms) of 52&#xa0;emu/g. The formulation demonstrated a high drug-loading efficiency of 72% and exhibited transferrin receptor–mediated cellular uptake in vitro. In vivo, treatment with the formulation led to significant cognitive enhancement in zebrafish, as evidenced by increased correct entries, reduced latency, and prolonged reward chamber occupancy, outperforming currently available formulations. Tf–SAMe–CA–SPIONs demonstrated excellent stability, efficient brain-targeted delivery, and marked improvement in cognitive function. By integrating targeted delivery, magnetic responsiveness, and neuroprotective effects, this multifunctional nanoplatform offers a promising theranostic strategy for the treatment and management of Alzheimer’s disease.</p> Graphical Abstract <p></p>

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DoE-driven development, characterisation, in-silico ADME, and evaluation of surface functionalized SPIONs for enhanced blood–brain barrier permeability and targeted delivery of S-adenosylmethionine

  • 期刊论文

  • 发表日期：

    2026年1月7日

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  • Nishabh Kushwaha,
  • Asha Patel,
  • Kshitija Akarte,
  • Nutan Shukla,
  • Zhengyou Li,
  • Shruti Patel,
  • Viral Patel,
  • Drishti Panjwani,
  • Mange Ram Yadav,
  • Anand Joshi

摘要

Alzheimer’s disease (AD) therapies remain limited by poor blood–brain barrier (BBB) penetration and modest cognitive recovery. This study aimed to develop and evaluate transferrin-conjugated S-adenosylmethionine-loaded citric acid-stabilized superparamagnetic iron oxide nanoparticles (Tf-SAMe-CA-SPIONs) as a targeted nanoplatform for brain delivery. SPIONs were synthesised by co-precipitation and optimised using a design of experiments approach. The formulation was characterised for physicochemical, magnetic, and structural attributes, and its BBB permeability and neuroprotective efficacy were assessed using in vitro and zebrafish AD models. The optimised SPIONs displayed hydrodynamic diameters of 58–71 nm (PDI < 0.33). Following citric acid stabilisation, the particle size increased to 111.3 nm (PDI 0.347, zeta potential –20.08 mV), while transferrin–SAMe conjugation further enlarged the particles to around 196.4 nm with a zeta potential of –28.28 mV. XRD confirmed the magnetite spinel crystalline structure, and VSM analysis verified their superparamagnetic behaviour with a saturation magnetisation (Ms) of 52 emu/g. The formulation demonstrated a high drug-loading efficiency of 72% and exhibited transferrin receptor–mediated cellular uptake in vitro. In vivo, treatment with the formulation led to significant cognitive enhancement in zebrafish, as evidenced by increased correct entries, reduced latency, and prolonged reward chamber occupancy, outperforming currently available formulations. Tf–SAMe–CA–SPIONs demonstrated excellent stability, efficient brain-targeted delivery, and marked improvement in cognitive function. By integrating targeted delivery, magnetic responsiveness, and neuroprotective effects, this multifunctional nanoplatform offers a promising theranostic strategy for the treatment and management of Alzheimer’s disease.

Graphical Abstract