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工程化热敏脂质磁性纳米颗粒用于在动物模型中时空递送达肝素到炎症部位。

Thermoresponsive lipids engineered magnetic nanoparticles for spatiotemporal delivery of hesperidin to inflammatory sites in animal model.

机构信息

International Center for Chemical and Biological Sciences, H.E.J Research Institute of Chemistry, University of Karachi, Karachi, Pakistan.

Molecular Pathology Section, Department of Pathology, Dow Diagnostic Reference and Research Laboratory, Dow University of Health Sciences, Karachi, Pakistan.

出版信息

Pharm Dev Technol. 2024 Sep;29(7):762-775. doi: 10.1080/10837450.2024.2393216. Epub 2024 Aug 26.

DOI:10.1080/10837450.2024.2393216
PMID:39143894
Abstract

Thermoresponsive nanoparticles are exploited as drug-delivery vehicles that release their payload upon increment in temperature. We prepared and characterized thermoresponsive lipid-anchored folic acid engineered magnetic nanoparticles (LP-HP-FANPs) that combine receptor-based targeting and thermoresponsive sustained release of hesperidin (HP) in response to endogenous inflammation site temperature. The progressive surface engineering of NPs was validated by FTIR analysis. Our LP-HP-FANPs had a particle size of 100.5 ± 1.76 nm and a zeta potential of 14.6 ± 2.65 mV. The HP encapsulation effectiveness of LP-HP-FANPs is around 91 ± 0.78%. AFM scans indicated that our modified nanoparticles were spherical. LP-HP-FANPs exhibit increased drug release (85.8% at pH 4.0, 50.9% at pH 7.0) at 40 °C. Animal studies showed no toxicity from nanoparticles. Compared to conventional drugs and HP, LP-HP-FANPs effectively decreased paw edema, cytokine levels, and total cell recruitment in thioglycollate-induced peritonitis ( < 0.05). LP-HP-FANPs substantially decreased cytokines compared to HP, HP-FA-NPs, and the standard medication ( < 0.05,  < 0.01, and  < 0.001). These findings imply that the synthesized HP-loaded formulation (LP-HP-FANPs) may be a potential anti-inflammatory formulation for clinical development.

摘要

热敏纳米粒子被用作药物递送载体,在温度升高时释放其有效载荷。我们制备并表征了热敏脂质锚定叶酸修饰的磁性纳米粒子(LP-HP-FANPs),它结合了基于受体的靶向和热敏持续释放橙皮苷(HP),以响应内源性炎症部位的温度。通过 FTIR 分析验证了 NPs 的渐进表面工程。我们的 LP-HP-FANPs 的粒径为 100.5 ± 1.76nm,zeta 电位为 14.6 ± 2.65mV。LP-HP-FANPs 的 HP 包封效率约为 91 ± 0.78%。AFM 扫描表明我们修饰的纳米粒子呈球形。LP-HP-FANPs 在 40°C 时表现出更高的药物释放(pH 4.0 时为 85.8%,pH 7.0 时为 50.9%)。动物研究表明纳米粒子没有毒性。与传统药物和 HP 相比,LP-HP-FANPs 能有效减轻巯基乙酸诱导的腹膜炎中的足肿胀、细胞因子水平和总细胞募集(<0.05)。与 HP、HP-FA-NPs 和标准药物相比,LP-HP-FANPs 显著降低了细胞因子(<0.05,<0.01 和<0.001)。这些发现表明,合成的 HP 负载配方(LP-HP-FANPs)可能是一种有潜力的用于临床开发的抗炎配方。

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