Design, fabrication, and in vitro-in vivo evaluation of surface-engineered pyrazinamide-loaded lipid nanoparticles for tuberculosis therapy.

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Nimitt V Chokshi, Preksha Vinchhi, Shreyansh Chauhan, Vivek Bora, Bhoomika M Patel, Mayur M Patel
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Abstract

Pyrazinamide (PYZ), a nicotinamide derivative, is an essential first-line anti-TB drug. However, its dose-dependent hepatotoxicity poses a considerable challenge, accentuating the need for improved delivery approaches. The key objective of the research work was to develop mannose-appended pyrazinamide-containing solid-lipid nanoparticles (Mn-PYZ-SNs) for the targeted management of TB. The developed Mn-PYZ-SNs depicted a particle size of 422±09 nm, which was slightly higher than that of unconjugated PYZ-SNs (Un-PYZ-SNs)(401±08 nm), with a minimal reduction in entrapment efficiency(83.64±1.42%). The in vitro drug release studies demonstrated comparable sustained release patterns for both formulations, with a similarity factor (f2) of 77.33, indicating that the structural integrity of PYZ-SNs was maintained during mannose conjugation. Fluorescence imaging and flow cytometric analysis revealed significantly enhanced cellular uptake of Mn-C6-SNs, with a 1.60-fold increase compared to Un-C6-SNs. The in vivo pharmacokinetic studies conducted on Sprague-Dawley rats showed a 4.7-fold improvement in relative bioavailability for Mn-PYZ-SNs. Biodistribution studies demonstrated significantly higher lung accumulation of Mn-PYZ-SNs (1.93-fold) compared to Un-PYZ-SNs at 24 hours. The aforementioned results imply that the developed Mn-PYZ-SNs could be a promising carrier for the treatment of TB. via the oral intestinal lymphatic pathway, circumventing its hepatic first-pass metabolism, and thereby preventing hepatic adverse effects.

设计,制造和体外体内评估表面工程吡嗪酰胺负载脂质纳米颗粒结核病治疗。
吡嗪酰胺(Pyrazinamide, PYZ)是一种烟酰胺衍生物,是必不可少的一线抗结核药物。然而,其剂量依赖性肝毒性构成了相当大的挑战,强调了改进给药方法的必要性。该研究工作的主要目标是开发含有甘露糖附加吡嗪酰胺的固体脂质纳米颗粒(Mn-PYZ-SNs),用于结核病的靶向治疗。制备的Mn-PYZ-SNs粒径为422±09 nm,略高于未共轭的Mn-PYZ-SNs (unpyz - sns)(401±08 nm),但包封效率略有下降(83.64±1.42%)。体外释药研究表明,两种制剂的缓释模式具有可比性,相似系数(f2)为77.33,表明PYZ-SNs在甘露糖偶联过程中保持了结构完整性。荧光成像和流式细胞分析显示,与Un-C6-SNs相比,Mn-C6-SNs的细胞摄取显著增加,增加了1.60倍。在Sprague-Dawley大鼠体内进行的药代动力学研究表明,Mn-PYZ-SNs的相对生物利用度提高了4.7倍。生物分布研究表明,24小时时Mn-PYZ-SNs的肺累积量明显高于Un-PYZ-SNs(1.93倍)。上述结果表明,所开发的Mn-PYZ-SNs可能是治疗结核病的一种有前景的载体。经口腔肠淋巴通路,绕过其肝脏首过代谢,从而防止肝脏不良反应。
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
CiteScore
5.90
自引率
2.90%
发文量
82
审稿时长
1 months
期刊介绍: Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology. Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as: -Preformulation and pharmaceutical formulation studies -Pharmaceutical materials selection and characterization -Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation -QbD in the form a risk assessment and DoE driven approaches -Design of dosage forms and drug delivery systems -Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies -Drug delivery systems research and quality improvement -Pharmaceutical regulatory affairs This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.
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