Transferrin functionalized poloxamer-chitosan nanoparticles of metformin: physicochemical characterization, in-vitro, and Ex-vivo studies.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2023-12-01 Epub Date: 2023-12-20 DOI:10.1080/03639045.2023.2282990

Swapnali Vasant Birajdar, Farhan Mazahir, Awesh K Yadav

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引用次数: 0

Abstract

Object: We report the preparation, characterization, and in-vitro therapeutic evaluation of Metformin-Loaded, Transferrin-Poloxamer-Functionalized Chitosan Nanoparticles (TPMC-NPs) for their repurposing in Alzheimer's disease (AD).

Significance: Usefulness of this work to establish the repurposing of metformin for the treatment of AD.

Methods: The TPMC-NPs were prepared by ionic gelation method using sodium tripolyphosphate. The modification and functionalization were confirmed by FTIR and ¹H^-NMR spectroscopy. The physicochemical characterization was performed using DLS, FTIR,¹H-NMR, CD spectroscopy, SEM, DSC, PXRD, HR-TEM, and hot-stage microscopy.

Results: The size, PDI, percent entrapment efficiency, and percent drug loading of TPMC-NPs were found to be 287.4 ± 9.5, 0.273 ± 0.067, 81.15 ± 7.17%, 11.75%±8.21%, respectively. Electron microscope analysis revealed smooth and spherical morphology. The transferrin conjugation efficiency was found to be 46% by the BCA method. CD spectroscopy confirmed no significant loss of the secondary structure of transferrin after conjugation. PXRD data indicated the amorphous nature of the TPMC-NPs. Hot-stage microscopy and DSC confirmed the thermal stability of TPMC-NPs. The in-vitro drug release showed a sustained release at pH 7.4. The DPPH assay displayed 80% antioxidant activity of TPMC-NPs in comparison with metformin and blank NPs. The in-vitro cytotoxicity assay revealed 69.60% viable SH- SY5Y cells at 100 µg/mL of TPMC NPs. The ex-vivo nasal ciliotoxicity and mucoadhesion studies showed no significant toxicity, and 98.16% adhesion, respectively. The nasal permeability study showed the release of metformin within 30 min from TPMC-NPs.

Conclusion: The obtained results suggested the usefulness of TPMC-NPs in the treatment of AD via the intranasal route.

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转铁蛋白功能化的poloxmer -壳聚糖纳米二甲双胍:理化表征，体外和离体研究。

目的:报道二甲双胍负载、转铁蛋白-波洛莫功能化壳聚糖纳米颗粒(TPMC-NPs)的制备、表征和体外治疗评价，并将其用于阿尔茨海默病(AD)的治疗。意义:本研究有助于确立二甲双胍治疗AD的重新用途。方法:采用三聚磷酸钠离子凝胶法制备TPMC-NPs。通过FTIR和1H-NMR证实了改性和功能化。采用DLS、FTIR、1H-NMR、CD谱、SEM、DSC、PXRD、HR-TEM和热级显微镜进行了理化表征。结果:TPMC-NPs的体积、PDI、包封率、载药量分别为287.4±9.5、0.273±0.067、81.15±7.17%、11.75%±8.21%。电镜分析显示其表面光滑，呈球形。BCA法发现转铁蛋白的结合效率为46%。CD光谱证实，偶联后转铁蛋白二级结构无明显损失。PXRD数据表明了TPMC-NPs的无定形性质。热级显微镜和DSC证实了TPMC-NPs的热稳定性。体外释药在pH为7.4时缓释。与二甲双胍和空白NPs相比，DPPH实验显示TPMC-NPs的抗氧化活性为80%。体外细胞毒性试验显示，在100µg/mL TPMC NPs下，SH- SY5Y细胞存活率为69.60%。离体鼻纤毛毒性和黏附性研究均显示无明显毒性，黏附性分别为98.16%。鼻腔渗透性研究显示，TPMC-NPs在30分钟内释放二甲双胍。结论:TPMC-NPs在经鼻给药治疗AD中有一定的应用价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464