Inhalable N-Acetylcysteine-loaded Lactose-coated PLGA Nanoparticles for Tuberculosis Treatment.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2025-07-10 DOI:10.1007/s11095-025-03889-1

Kabi Raj Chaudhary, Cláudia Viegas, Paola Pirela, Mariana Atalaia, Beatriz Ruivinho, Sanchit Arora, Arti Singh, Pedro Brandão, Charan Singh, Pedro Fonte

{"title":"Inhalable N-Acetylcysteine-loaded Lactose-coated PLGA Nanoparticles for Tuberculosis Treatment.","authors":"Kabi Raj Chaudhary, Cláudia Viegas, Paola Pirela, Mariana Atalaia, Beatriz Ruivinho, Sanchit Arora, Arti Singh, Pedro Brandão, Charan Singh, Pedro Fonte","doi":"10.1007/s11095-025-03889-1","DOIUrl":null,"url":null,"abstract":"Objective: Glutathione (GSH), known for having mucolytic, anti-inflammatory, and antioxidant activities, is used in clinical practice in several pathologies, including tuberculosis (TB). N-acetylcysteine (NAC) has been primarily used to treat lung conditions and paracetamol-induced liver toxicity. However, NAC exhibits potential antimycobacterial activity through several mechanisms including immunomodulation, enhancement of GSH levels, and direct antimycobacterial effect. In this work, we aim to develop an effective drug delivery system for NAC for inhalable formulations.Methods: Herein, we report the development of lactose-coated NAC-loaded Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NAC-PLGA NPs) obtained by double emulsion methodology. Lactose has a double role, as a cryoprotectant agent and dispersant for inhalable formulations. The physicochemical properties of lactose-coated NAC-PLGA NPs were examined in terms of particle size, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency, and morphology. The in vitro release and lung deposition studies were assessed.Results: The physicochemical characterization studies revealed the compatibility of the drug with the selected excipients. Moreover, lactose-coated NAC-PLGA NPs showed particle size of 310 ± 3 nm, PdI of 0.15 ± 0.01, and of -11.5 ± 0.4 mV. The in vitro release study suggested a biphasic release profile. Likewise, in vitro lung deposition studies revealed desirable lung deposition parameters, indicating effective particle size for efficient pulmonary delivery. Additionally, in vitro studies for antimycobacterial activity exhibited superior antibacterial activity against Mycobacterium Tuberculosis (MTB) H37Rv.Conclusions: These preliminary findings suggest that lactose-coated NAC-PLGA NPs can open the door to new therapeutic options against one of the most drug-refractory and drug-resistant infectious diseases, TB.","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11095-025-03889-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Glutathione (GSH), known for having mucolytic, anti-inflammatory, and antioxidant activities, is used in clinical practice in several pathologies, including tuberculosis (TB). N-acetylcysteine (NAC) has been primarily used to treat lung conditions and paracetamol-induced liver toxicity. However, NAC exhibits potential antimycobacterial activity through several mechanisms including immunomodulation, enhancement of GSH levels, and direct antimycobacterial effect. In this work, we aim to develop an effective drug delivery system for NAC for inhalable formulations.

Methods: Herein, we report the development of lactose-coated NAC-loaded Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NAC-PLGA NPs) obtained by double emulsion methodology. Lactose has a double role, as a cryoprotectant agent and dispersant for inhalable formulations. The physicochemical properties of lactose-coated NAC-PLGA NPs were examined in terms of particle size, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency, and morphology. The in vitro release and lung deposition studies were assessed.

Results: The physicochemical characterization studies revealed the compatibility of the drug with the selected excipients. Moreover, lactose-coated NAC-PLGA NPs showed particle size of 310 ± 3 nm, PdI of 0.15 ± 0.01, and of -11.5 ± 0.4 mV. The in vitro release study suggested a biphasic release profile. Likewise, in vitro lung deposition studies revealed desirable lung deposition parameters, indicating effective particle size for efficient pulmonary delivery. Additionally, in vitro studies for antimycobacterial activity exhibited superior antibacterial activity against Mycobacterium Tuberculosis (MTB) H37Rv.

Conclusions: These preliminary findings suggest that lactose-coated NAC-PLGA NPs can open the door to new therapeutic options against one of the most drug-refractory and drug-resistant infectious diseases, TB.

查看原文本刊更多论文

可吸入n -乙酰半胱氨酸负载的乳糖包被PLGA纳米颗粒用于结核病治疗。

目的：谷胱甘肽（GSH）以具有溶黏液、抗炎和抗氧化活性而闻名，在临床实践中用于多种疾病，包括结核病（TB）。n -乙酰半胱氨酸（NAC）主要用于治疗肺部疾病和扑热息痛引起的肝毒性。然而，NAC通过多种机制表现出潜在的抗细菌活性，包括免疫调节、增强谷胱甘肽水平和直接的抗细菌作用。在这项工作中，我们的目标是开发一种有效的NAC可吸入制剂给药系统。方法：本文报道了采用双乳法制备的乳糖包被负载聚乳酸-羟基乙酸（PLGA）纳米粒子（NAC-PLGA NPs）。乳糖具有双重作用，作为可吸入配方的冷冻保护剂和分散剂。从粒径、多分散性指数（PdI）、ζ电位（ZP）、包封效率和形态等方面考察了乳糖包被的NAC-PLGA NPs的理化性质。评估了体外释放和肺沉积研究。结果：对所选辅料进行了理化性质研究，结果表明该制剂与所选辅料具有良好的配伍性。此外，乳糖包被NAC-PLGA NPs的粒径为310±3 nm， PdI为0.15±0.01,-11.5±0.4 mV。体外释放研究表明其为双相释放。同样，体外肺沉积研究揭示了理想的肺沉积参数，表明了有效的肺输送颗粒大小。此外，体外抗细菌活性研究显示出对结核分枝杆菌（MTB） H37Rv具有优越的抗菌活性。结论：这些初步研究结果表明，乳糖包被的NAC-PLGA NPs可以为治疗最耐药和耐药的传染病之一结核病打开新的治疗选择的大门。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.