Prakash Kumar Sirvi, Paul Gajanan Balaji, Amit Kumar, Md Imtiyaz Alam, Ankita Sharma, Nabanita Das, Awesh Kumar Yadav
{"title":"乳铁蛋白锚定的羧甲基普鲁兰-氧化镁纳米复合材料靶向递送反式阿魏酸：物理化学表征，体外和离体研究。","authors":"Prakash Kumar Sirvi, Paul Gajanan Balaji, Amit Kumar, Md Imtiyaz Alam, Ankita Sharma, Nabanita Das, Awesh Kumar Yadav","doi":"10.1021/acsabm.5c00482","DOIUrl":null,"url":null,"abstract":"<p><p>The design of efficacious nanotherapeutics for neurodegenerative disorders necessitates the development of precisely targeted delivery systems capable of transversing the blood-brain barrier (BBB) while sustaining therapeutic efficacy. Here, we introduce a novel brain-targeted nanocomposite system comprising carboxymethylated pullulan-magnesium oxide (CMP-MgO) matrix encapsulating trans-ferulic acid (TFA) and last surface-functionalized with lactoferrin (Lf) to facilitate receptor-mediated transcytosis. Comprehensive physicochemical characterization, including dynamic light scattering (DLS), proton-nuclear magnetic resonance (<sup>1</sup>H NMR), fourier transform infrared (FT-IR), high resolution-transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), and circular dichroism (CD) spectroscopy, confirmed the structural integrity functionalization, and stability of the nanocomposites. DLS studies exhibited a hydrodynamic diameter of 386 ± 5.06 nm, a polydispersity index of 0.087 ± 0.008, and a zeta potential of -20.5 ± 0.19 mV of the Lf-TFA-CMP-MgO. Morphological analysis confirmed spherical particles with a smooth surface, and CD spectroscopy confirmed the perpetuation of the native structure of Lf after conjugation with the nanocomposite. The antioxidant assay highlighted significant free radical scavenging activity, reflecting the antioxidant potential of TFA and TFA-loaded nanocomposites. <i>In vitro</i> studies demonstrated excellent biocompatibility and enhanced cellular internalization due to Lf functionalization. Notably, the nanocomposite inhibited amyloid fibril formation by interacting with hen egg white lysozyme (HEWL). Furthermore, intranasal delivery achieved efficient nose-to-brain transport, with permeability of 415.45 μg/cm<sup>2</sup> at 6 h, highlighting its mucoadhesive properties and noninvasive therapeutic capability for Alzheimer's disease (AD).</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"5757-5774"},"PeriodicalIF":4.7000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lactoferrin-Anchored Carboxymethyl Pullulan-MgO Nanocomposites for Targeted Delivery of Trans-Ferulic Acid: Physicochemical Characterization, In vitro and Ex vivo Studies.\",\"authors\":\"Prakash Kumar Sirvi, Paul Gajanan Balaji, Amit Kumar, Md Imtiyaz Alam, Ankita Sharma, Nabanita Das, Awesh Kumar Yadav\",\"doi\":\"10.1021/acsabm.5c00482\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The design of efficacious nanotherapeutics for neurodegenerative disorders necessitates the development of precisely targeted delivery systems capable of transversing the blood-brain barrier (BBB) while sustaining therapeutic efficacy. Here, we introduce a novel brain-targeted nanocomposite system comprising carboxymethylated pullulan-magnesium oxide (CMP-MgO) matrix encapsulating trans-ferulic acid (TFA) and last surface-functionalized with lactoferrin (Lf) to facilitate receptor-mediated transcytosis. Comprehensive physicochemical characterization, including dynamic light scattering (DLS), proton-nuclear magnetic resonance (<sup>1</sup>H NMR), fourier transform infrared (FT-IR), high resolution-transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), and circular dichroism (CD) spectroscopy, confirmed the structural integrity functionalization, and stability of the nanocomposites. DLS studies exhibited a hydrodynamic diameter of 386 ± 5.06 nm, a polydispersity index of 0.087 ± 0.008, and a zeta potential of -20.5 ± 0.19 mV of the Lf-TFA-CMP-MgO. Morphological analysis confirmed spherical particles with a smooth surface, and CD spectroscopy confirmed the perpetuation of the native structure of Lf after conjugation with the nanocomposite. The antioxidant assay highlighted significant free radical scavenging activity, reflecting the antioxidant potential of TFA and TFA-loaded nanocomposites. <i>In vitro</i> studies demonstrated excellent biocompatibility and enhanced cellular internalization due to Lf functionalization. Notably, the nanocomposite inhibited amyloid fibril formation by interacting with hen egg white lysozyme (HEWL). 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Lactoferrin-Anchored Carboxymethyl Pullulan-MgO Nanocomposites for Targeted Delivery of Trans-Ferulic Acid: Physicochemical Characterization, In vitro and Ex vivo Studies.
The design of efficacious nanotherapeutics for neurodegenerative disorders necessitates the development of precisely targeted delivery systems capable of transversing the blood-brain barrier (BBB) while sustaining therapeutic efficacy. Here, we introduce a novel brain-targeted nanocomposite system comprising carboxymethylated pullulan-magnesium oxide (CMP-MgO) matrix encapsulating trans-ferulic acid (TFA) and last surface-functionalized with lactoferrin (Lf) to facilitate receptor-mediated transcytosis. Comprehensive physicochemical characterization, including dynamic light scattering (DLS), proton-nuclear magnetic resonance (1H NMR), fourier transform infrared (FT-IR), high resolution-transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), and circular dichroism (CD) spectroscopy, confirmed the structural integrity functionalization, and stability of the nanocomposites. DLS studies exhibited a hydrodynamic diameter of 386 ± 5.06 nm, a polydispersity index of 0.087 ± 0.008, and a zeta potential of -20.5 ± 0.19 mV of the Lf-TFA-CMP-MgO. Morphological analysis confirmed spherical particles with a smooth surface, and CD spectroscopy confirmed the perpetuation of the native structure of Lf after conjugation with the nanocomposite. The antioxidant assay highlighted significant free radical scavenging activity, reflecting the antioxidant potential of TFA and TFA-loaded nanocomposites. In vitro studies demonstrated excellent biocompatibility and enhanced cellular internalization due to Lf functionalization. Notably, the nanocomposite inhibited amyloid fibril formation by interacting with hen egg white lysozyme (HEWL). Furthermore, intranasal delivery achieved efficient nose-to-brain transport, with permeability of 415.45 μg/cm2 at 6 h, highlighting its mucoadhesive properties and noninvasive therapeutic capability for Alzheimer's disease (AD).
期刊介绍：
ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications.
The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
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