壳聚糖-地尔硫卓纳米颗粒抗肺纤维化的硅、体外和体内评估。

IF 2.2 Q2 PHARMACOLOGY & PHARMACY

Therapeutic delivery Pub Date : 2025-06-01 Epub Date: 2025-03-24 DOI:10.1080/20415990.2025.2478803

Nandeeni Punase, Ganesh V Jamdar, Ghanshyam Mapare, Vishal S Patil, Narendra Nagpure, Niharika Patil, Chandrakantsing V Pardeshi, Chandragouda R Patil

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引用次数: 0

摘要

目的：地尔硫卓（DIL）是一种钙通道阻滞剂，已被证明具有抑制纤维化相关过程的潜力，包括TGF-β激活、胶原生成和上皮-间质转化，使其成为特发性肺纤维化（IPF）的有希望的候选药物。本研究通过分子和实验两种方法对负载dil的壳聚糖（DIL-CHT）和三甲基壳聚糖（DIL-TMC）纳米颗粒的抗纤维化效果进行了评价。方法：制备DIL-CHT和DIL-TMC纳米制剂，并对其粒径、ζ电位、包封效率和体外释放度进行分析。在博来霉素（BLM）诱导的IPF大鼠模型中，研究了亚治疗剂量（3 mg/kg/天，每日）和单独使用DIL （10 mg/kg/天，每日）的抗纤维化效果。通过DFT （B3LYP/6-31 G**）优化和分子对接来评估CHT、TMC和DIL之间的电子性质和相互作用。结果：DIL-TMC和DIL-CHT纳米颗粒粒径分别为175.6 nm和267.8 nm，包封效率分别为81.72%和66.0%；TMC表现出较好的24小时持续释放。TMC更大的HOMO-LUMO间隙（ΔE = -0.260 eV vs. CHT = -0.253 eV）表明更大的稳定性，支持其与DIL增强的相互作用。TMC纳米颗粒显著降低BLM诱导的IPF症状，即BLM诱导的肺指数升高、羟脯氨酸积累、肺组织氧化应激和血压升高。结论：这些发现表明DIL-TMC治疗IPF的潜力很大，且心血管副作用最小。

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In silico, in vitro, and in vivo assessment of chitosan-diltiazem nanoparticles against pulmonary fibrosis.

Aims: Diltiazem (DIL), a calcium channel blocker, has demonstrated potential ininhibiting fibrosis-related processes, including TGF-β activation, collagen production, and epithelial-mesenchymal transition, making it a promising candidate for idiopathic pulmonary fibrosis (IPF). This study evaluates the anti-fibrotic efficacy of DIL-loaded chitosan (DIL-CHT) and trimethyl chitosan (DIL-TMC) nanoparticles through molecular and experimental approaches.

Methods: DIL-CHT and DIL-TMC nanoformulations were developed and analyzed particle size, ζ-potential, entrapment efficiency, and in vitro release. Antifibrotic efficacy in bleomycin (BLM)-induced IPF rat model, was tested at subtherapeutic doses (3 mg/kg/day, i.t.) and DIL alone (10 mg/kg/day, p.o.). DFT (B3LYP/6-31 G**) optimization and molecular docking were conducted to assess electronic properties and interactions among CHT, TMC, and DIL.

Results: DIL-TMC and DIL-CHT nanoparticles were 175.6 nm and 267.8 nm, with entrapment efficiencies of 81.72% and 66.0%, respectively; TMC showed a superior 24-hour sustained release. TMC's larger HOMO-LUMO gap (ΔE = -0.260 eV vs. -0.253 eV for CHT) suggests greater stability, supporting its enhanced interaction with DIL. TMC nanoparticles significantly reduced BLM-induced IPF symptoms, i.e. BLM induced increased lung index, hydroxyproline accumulation, oxidative stress in lung tissue, and blood pressure.

Conclusions: These findings indicate the strong therapeutic potential of DIL-TMC for IPF with minimal cardiovascular side effects.

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来源期刊

Therapeutic delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.50

自引率

0.00%

发文量

期刊介绍： Delivering therapeutics in a way that is right for the patient - safe, painless, reliable, targeted, efficient and cost effective - is the fundamental aim of scientists working in this area. Correspondingly, this evolving field has already yielded a diversity of delivery methods, including injectors, controlled release formulations, drug eluting implants and transdermal patches. Rapid technological advances and the desire to improve the efficacy and safety profile of existing medications by specific targeting to the site of action, combined with the drive to improve patient compliance, continue to fuel rapid research progress. Furthermore, the emergence of cell-based therapeutics and biopharmaceuticals such as proteins, peptides and nucleotides presents scientists with new and exciting challenges for the application of therapeutic delivery science and technology. Successful delivery strategies increasingly rely upon collaboration across a diversity of fields, including biology, chemistry, pharmacology, nanotechnology, physiology, materials science and engineering. Therapeutic Delivery recognizes the importance of this diverse research platform and encourages the publication of articles that reflect the highly interdisciplinary nature of the field. In a highly competitive industry, Therapeutic Delivery provides the busy researcher with a forum for the rapid publication of original research and critical reviews of all the latest relevant and significant developments, and focuses on how the technological, pharmacological, clinical and physiological aspects come together to successfully deliver modern therapeutics to patients. The journal delivers this essential information in concise, at-a-glance article formats that are readily accessible to the full spectrum of therapeutic delivery researchers.