甘露糖基化壳聚糖修饰的PLGA纳米颗粒靶向肺递送异烟肼:治疗结核病的一种有前途的方法。

IF 3.9 4区 医学 Q1 PHARMACOLOGY & PHARMACY
Riffat Maqbool, Dur E Nayab, Muhammad Mubeen, Hussain Ali, Salman Khan
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引用次数: 0

摘要

由结核分枝杆菌(M. TB)引起的结核病是对全球卫生的重大挑战。该疾病的治疗需要延长抗生素治疗疗程,持续时间为6至9个月。这些方案的复杂性和持续时间经常导致显著的不良反应,胃肠道问题和耐药性的发展。为了解决这些挑战,我们设计了基于纳米颗粒的可吸入给药系统,通过合成甘露糖化壳聚糖修饰的PLGA纳米颗粒,装载异烟肼(MC-PLGA-INH-PNPs),用于靶向肺部给药。因此,基于纳米颗粒的药物递送系统提供了靶向并将负载药物直接递送到结核分枝杆菌感染细胞中的潜力。优化后的纳米配方粒径为154.9±21 nm, zeta电位为-23.2±0.52 mV,包封效率为79.8%±0.45。此外,MC-PLGA-INH-PNPs在生理pH 7.4下持续释放药物24小时。利用脂多糖作为诱导剂,在小鼠模型上对MC-PLGA-INH-PNPs进行了体内研究。从体内研究中获得的数据显示,肺组织结构有了实质性的改善,炎症也减少了。与纯药物治疗组相比,使用MC-PLGA-INH-PNPs治疗组的动物在疾病恢复方面表现出显着改善。这些发现进一步表明,这些可吸入的MC-PLGA-INH-PNPs在治疗结核病方面具有很好的策略,并大大改善了肺部药物向靶部位的输送。然而,在其他相关动物模型上对这种纳米制剂的详细调查和测试将是成功地将这一概念从实验室转化为临床实践的关键。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mannosylated chitosan-decorated PLGA nanoparticles for targeted pulmonary delivery of isoniazid: a promising approach in the treatment of tuberculosis.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), represents a significant challenge to global health. The management of the disease requires an extended course of antibiotic therapy, spanning a duration of 6 to 9 months. The complexity and duration of these regimens frequently lead to significant adverse effects, gastrointestinal issues, and the development of drug resistance. To address these challenges, the nanoparticulate based inhalable drug delivery system was designed as such by synthesising mannosylated chitosan decorated PLGA nanoparticles loaded with isoniazid (MC-PLGA-INH-PNPs) for targeted pulmonary delivery. Hence, nanoparticle based drug delivery system offers the potential to target and deliver the loaded drug directly into the M.tb infected cells. The prepared and optimised nano-formulation had a particle size of 154.9 ± 21 nm, zeta potential -23.2 ± 0.52 mV and entrapment efficiency of 79.8% ± 0.45. Additionally, the MC-PLGA-INH-PNPs exhibited a sustained drug release profile at physiological pH 7.4 for a period of 24 hr. An in vivo study of the MC-PLGA-INH-PNPs was performed on a mouse model utilising lipopolysaccharide as an inducer. The data obtained from the in vivo studies showed substantial improvements in lung tissues architecture and reduced inflammation. The group of animals treated with the MC-PLGA-INH-PNPs showed significant improvement in restoration of the disease when compared to pure drug treated group. These findings further indicate that these inhalable MC-PLGA-INH-PNPs hold a promising strategy for the treatment of tuberculosis and considerably improves pulmonary drug delivery to the target site. However, detailed investigations and testing of this nano-formulation on other relevant animal models will be essential to successfully translate this concept from laboratory to clinical practice.

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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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