“探索阿魏酸负载纳米结构脂质载体的潜力:通过对接、配方、药代动力学和药效学研究抑制血管紧张素”。

IF 4.3 4区 医学 Q1 PHARMACOLOGY & PHARMACY Journal of Drug Targeting Pub Date : 2025-01-29 DOI:10.1080/1061186X.2025.2453743
Preeti Rajabhau Meshram, Nisharani Sudhakar Ranpise
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引用次数: 0

摘要

阿魏酸(FA)是一种天然获得的酚类化合物,是一种多功能抗氧化剂,具有治疗高血压的潜力。然而,由于其分类为BCS IV类片段,其应用受到限制。为了解决这一问题,我们利用乳化探针超声技术开发了FA的纳米结构脂质载体(nlc),以提高其溶解度和渗透性。以硬脂酸和Labrasol脂质、表面活性剂Tween 80、超声时间为研究对象,采用Box-Behnken设计优化配方。评估FA-NLCs的粒径、zeta电位、PDI、包封效率和体外释放。对雄性Wistar大鼠进行了药代动力学和肠道摄取研究。采用高果糖饮食模型对Sprague Dawley大鼠高血压进行药效学研究。结果表明,FA与ACE受体(1UZF)之间存在较强的相互作用,对接分数为-7.144 kcal/mol,结合能为-54.624 kcal/mol。优化后的配方(F12 FA-NLC)粒径为103.4±8.89 nm, zeta电位为-43.6 mV,多分散指数为0.531±0.021,包封效率为88.90±6.27%。体外释药研究表明,普通FA在4小时内释药量为103.13±8.80%,而FA- nlcs在24小时内释药量为40.34±5.35%,为缓释。FA- nlc的药代动力学研究显示,与纯FA相比,cmax增加2.6倍,AUC和半衰期增加1.9倍,这是非常显著的(p)肠道吸收结果强调通过网状蛋白介导的内吞作用,通过淋巴吸收,绕过第一过代谢,从而提高了治疗效果。因此,该研究得出结论,与普通FA相比,FA- nlc可有效降低血压。
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Exploring the potential of ferulic acid-loaded nanostructured lipid carriers: angiotensin inhibition via docking, formulation and pharmacokinetic and pharmacodynamics studies.

Ferulic acid (FA) is a natural phenolic compound that has been documented for its antioxidant properties and potential in managing hypertension. However, its use is limited due to poor solubility and permeability (BCS Class IV classification). To overcome this, nanostructured lipid carriers (NLCs) of FA were developed using the emulsification probe sonication technique, with formulation optimized through Box-Behnken design. The optimized FA-NLCs (F12) demonstrated a particle size of 103.4 nm, zeta potential of -43.6 mV, polydispersity index of 0.531, and entrapment efficiency of 88.9%. Key Findings of the research manifested, that during in-vitro release studies, FA-NLCs showed sustained release action (40.34% over 24 h) compared to plain FA (103.13% in 4 h). Pharmacokinetics of FA-NLC suggested that increased Cmax by 2.6-fold, AUC by 1.9-fold, and half-life significantly (p < .001), also Pharmacodynamics revealed that FA-NLCs reduced blood pressure more effectively (39.9 mmHg vs. 30.8 mmHg for plain FA; p < .001). Furthermore, FA-NLC was showing successful intestinal uptake through lymphatic absorption via clathrin-mediated endocytosis, bypassing first-pass metabolism, hence showed enhancement in bioavailability, Thus the study concluded that FA-NLCs significantly improve therapeutic efficacy and sustained blood pressure reduction compared to plain FA.

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来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
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