Current Research in Pharmacology and Drug Discovery最新文献

{"title":"miRNA nanoencapsulation to regulate the programming of the blood-brain barrier permeability by hypoxia","authors":"Esteban G. Figueroa ,&nbsp;Aitor Caballero-Román ,&nbsp;Josep R. Ticó ,&nbsp;Montserrat Miñarro ,&nbsp;Anna Nardi-Ricart ,&nbsp;Alejandro González-Candia","doi":"10.1016/j.crphar.2022.100129","DOIUrl":"10.1016/j.crphar.2022.100129","url":null,"abstract":"<div><p>Central nervous system (CNS)-related diseases are difficult to treat as most therapeutic agents they cannot reach the brain tissue, mainly due to the blood-brain barrier (BBB), arguably the tightest barrier between the human body and cerebral parenchyma, which routinely excludes most xenobiotic therapeutics compounds. The BBB is a multicellular complex that structurally forms the neurovascular unit (NVU) and is organized by neuro-endothelial and glial cells. BBB breakdown and dysfunction from the cerebrovascular cells lead to leakages of systemic components from the blood into the CNS, contributing to neurological deficits. Understanding the molecular mechanisms that regulate BBB permeability and disruption is essential for establishing future therapeutic strategies to restore permeability and improve cerebrovascular health. MicroRNAs (miRNAs), a type of small non-coding RNAs, are emerging as an important regulator of BBB integrity by modulating gene expression by targeting mRNA transcripts. miRNAs is implicated in the development and progression of various illnesses. Conversely, nanoparticle carriers offer unprecedented opportunities for cell-specific controlled delivery of miRNAs for therapeutic purposes. In this sense, we present in this graphical review critical evidence in the regulation of cell junction expression mediated by miRNAs induced by hypoxia and for the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of BBB permeability.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100129"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9780061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10428212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising effects of emoxypine and its succinate derivative in the management of various diseases-with insights on recent patent applications","authors":"Dhruv Sanjay Gupta,&nbsp;Siddhi Bagwe Parab,&nbsp;Ginpreet Kaur","doi":"10.1016/j.crphar.2022.100121","DOIUrl":"10.1016/j.crphar.2022.100121","url":null,"abstract":"<div><p>Emoxypine and its succinate derivative share a common hydroxypridine structure, which is similar to pyridoxine. These compounds have been utilized therapeutically and industrially, owing to the wide range of properties offered. This includes antihypoxic, neuroprotective and cardioprotective effects, along with pharmacokinetic benefits such as the ability to cross the blood brain barrier (BBB), owing to its relatively small size and low molecular weight. It was observed that emoxypine exhibited iron chelating property in vitro, indicating its usage as a promising therapeutic strategy in the management of neurodegenerative conditions such as Alzheimer's disease (AD), as well as hematologic disorders like thalassemia and hemochromatosis. In addition to this, it has been observed to exert a potent antioxidant effect, therefore, it may be considered for the amelioration of disorders resulting from free radical injury. Studies on its mechanism of action and implications on cellular and molecular levels would help to further the understanding of its benefits, as well as prospects for filing patents for novel applications. The primary focus of this review is to shed light on the broad spectrum of pharmacological properties offered by emoxypine and its succinate derivative, and to highlight the scope for an increased number of pre-clinical and clinical trials to assess its safety and efficacy. In addition to this, the highlights of this article include the recent patents filed and scope for novel applications of these agents.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ee/28/main.PMC9389226.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40433136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state","authors":"Amit A. Joharapurkar,&nbsp;Vishal J. Patel,&nbsp;Samadhan G. Kshirsagar,&nbsp;Maulik S. Patel,&nbsp;Hardikkumar H. Savsani,&nbsp;Chetan Kajavadara,&nbsp;Darshan Valani,&nbsp;Mukul R. Jain","doi":"10.1016/j.crphar.2022.100102","DOIUrl":"10.1016/j.crphar.2022.100102","url":null,"abstract":"<div><p>Many anemic chronic kidney disease (CKD) patients are refractory to erythropoietin (EPO) effects due to inflammation, deranged iron utilization, and generation of EPO antibodies. This work assessed the effect of desidustat, an inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase (PHD), on EPO-refractory renal anemia. Sprague Dawley rats were made anemic by cisplatin (5 ​mg/kg, IP, single dose) and turpentine oil (5 ​mL/kg, SC, once a week). These rats were given recombinant human EPO (rhEPO, 1 ​μg/kg) and desidustat (15 or 30 ​mg/kg) for eight weeks. Separately, rhEPO (1–5 ​μg/kg) was given to anemic rats to sustain the normal hemoglobin levels and desidustat (15 ​mg/kg) for eight weeks. In another experiment, the anemic rats were treated rhEPO (5 ​μg/kg) for two weeks and then desidustat (15 ​mg/kg) for the next two weeks. Dosing of rhEPO was thrice a week, and for desidustat, it was on alternate days. Desidustat inhibited EPO-resistance caused by rhEPO treatment, decreased hepcidin, IL-6, IL-1β, and increased iron and liver ferroportin. Desidustat reduced EPO requirement and anti-EPO antibodies. Desidustat also maintained normal hemoglobin levels after cessation of rhEPO treatment. Thus, novel prolyl hydroxylase inhibitor desidustat can treat EPO resistance via improved iron utilization and decreased inflammation.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100102"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000220/pdfft?md5=7ab92260618d2528e7ce75ad5d1111c5&pid=1-s2.0-S2590257122000220-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41974337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myrtenal mitigates streptozotocin-induced spatial memory deficit via improving oxido inflammatory, cholinergic and neurotransmitter functions in mice","authors":"Isaac Oluwatobi Akefe ,&nbsp;Victoria Aderonke Adegoke ,&nbsp;Ibrahim Yusuf Lamidi ,&nbsp;Matthew Phillip Ameh ,&nbsp;Enokela Shaibu Idoga ,&nbsp;Simon Azubuike Ubah ,&nbsp;Itopa Etudaye Ajayi","doi":"10.1016/j.crphar.2022.100106","DOIUrl":"10.1016/j.crphar.2022.100106","url":null,"abstract":"<div><p>The occurrence of chronic neurodegenerative disorders is on the rise, but with no effective treatment due to the paucity of information on the pathological mechanism underlying these disorders. Thus, this study investigated the role of oral administration of myrtenal in mitigating memory deficits and neuro-biochemical alterations in streptozotocin-demented mice model. Mice (n ​= ​35) were randomly allocated into five cohorts consisting of 7 mice each; Group I: Control mice received vehicle alone; Group II: streptozotocin; Group III: streptozotocin + 100 ​mg/kg myrtenal; Group IV: streptozotocin +200 ​mg/kg myrtenal; and Group V: streptozotocin ​+ ​donepezil 0.5 ​mg/kg. Data from this study demonstrated that the administration of streptozotocin (STZ) impaired spatial memory and induced alterations in markers of oxido-inflammatory response, cholinergic function, cytoarchitecture, and neurotransmitter levels in mice hippocampus. Notably, administration of myrtenal enhanced spatial memory performance in STZ-demented mice by improving the activities of endogenous antioxidant enzymes to protect the brain from oxido-inflammatory stress. Treatment with myrtenal also restored cholinergic function and stabilized the homeostasis of neurotransmitters in STZ-demented mice. The authors infer that fruits rich in myrtenal may be beneficial for treating patients living with dementia associated with Alzheimer's disease.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000268/pdfft?md5=f51bbb2d7e71d0a63efbfd94dea8f1e3&pid=1-s2.0-S2590257122000268-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45827127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Managing complex perianal disease after anti-TNF failure: Where to go next?","authors":"Clare Yzet ,&nbsp;Franck Brazier ,&nbsp;Charles Sabbagh ,&nbsp;Mathurin Fumery","doi":"10.1016/j.crphar.2022.100081","DOIUrl":"10.1016/j.crphar.2022.100081","url":null,"abstract":"<div><p>Crohn's disease is a chronic inflammatory bowel disease that affects various intestinal segments and can involve the perianal region. Although anti-tumor necrosis factor (TNF) agents have revolutionized the management of Crohn's disease and improved the prognosis for patients with perianal Crohn's disease (pCD), their long-term effectiveness is limited: over 60% of patients relapse after one year of maintenance therapy. In recent years, significant advances have been made in the treatment of complex perianal fistulas after anti-TNF failure. Concomitant treatment with antibiotics and immunosuppressants improves the effectiveness of anti-TNF agents. Therapeutic drug monitoring and dose adjustment of anti-TNF therapy (targeting a higher trough level) might also improve treatment response. Novel therapeutic strategies might provide new opportunities for pCD management; for example, ustekinumab might be effective after anti-TNF treatment failure, although more studies are needed. As suggested in recent international guidelines, mesenchymal stem cell injection might be an effective, safe treatment for complex pCD.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fd/75/main.PMC8784625.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39879602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of rapid intravenous paracetamol infusion in paediatric patients","authors":"Astrid Eliasen ,&nbsp;Sigrid Otnes ,&nbsp;Merete Matz ,&nbsp;Lise Aunsholt ,&nbsp;René Mathiasen","doi":"10.1016/j.crphar.2021.100077","DOIUrl":"10.1016/j.crphar.2021.100077","url":null,"abstract":"<div><h3>Purpose</h3><p>Paracetamol is recommended as a first-line treatment for pain and fever in paediatric patients. Intravenous (IV) infusions are recommended to be administered as a 15-min infusion to minimize local tissue trauma and related pain. The purpose of this study was to demonstrate that IV paracetamol could be administered during 5 ​min or less in paediatric patients without causing related adverse reactions.</p></div><div><h3>Methods</h3><p>Prospective, observational safety study including children aged &lt;18 years who received IV paracetamol. Pain scores before and after the paracetamol infusions were obtained using VAS, FLACC, COMFORT neo, or COMFORT behaviour scales with scores from 0 to 10 representing no pain to worst pain. Further, objective signs of inflammation at the infusion site were registered.</p></div><div><h3>Findings</h3><p>We included 44 patients (median age 2.8 years, range 0.01–17.0 years) who received paracetamol in a peripheral venous catheter (n ​= ​22) or central venous catheter (n ​= ​22). In total, the 93 paracetamol infusions had a median infusion time of 3:00 ​min, range 0:40 to 5:00 ​min. After infusions, pain scores were lower, compared to before infusions (mean change −0.26, 95% confidence interval −0.45 to −0.07, <em>P</em> ​= ​0.007), and no objective signs of inflammation were reported.</p></div><div><h3>Implications</h3><p>This safety study indicates that IV paracetamol can be administered in paediatric patients with a shorter infusion time than recommended without causing adverse reactions. The results may contribute to a more efficient workflow at paediatric departments.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal sialylation and fucosylation of saliva glycoproteins: Characteristics of lung cancer-specific biomarkers","authors":"Ziyuan Gao ,&nbsp;Mingming Xu ,&nbsp;Shuang Yue ,&nbsp;Huang Shan ,&nbsp;Jun Xia ,&nbsp;Junhong Jiang ,&nbsp;Shuang Yang","doi":"10.1016/j.crphar.2021.100079","DOIUrl":"10.1016/j.crphar.2021.100079","url":null,"abstract":"<div><p>Dysregulated surface glycoproteins play an important role in tumor cell proliferation and progression. Abnormal glycosylation of these glycoproteins may activate tumor signal transduction and lead to tumor development. The tumor microenvironment alters its molecular composition, some of which regulate protein glycosylation biosynthesis. The glycosylation of saliva proteins in lung cancer patients is different from healthy controls, in which the glycans of cancer patients are highly sialylated and hyperfucosylated. Most studies have shown that O-glycans from cancer are truncated O-glycans, while N-glycans contain fucoses and sialic acids. Because glycosylation analysis is challenging, there are few reports on how glycosylation of saliva proteins is related to the occurrence or progression of lung cancer. In this review, we discussed glycoenzymes involved in protein glycosylation, their changes in tumor microenvironment, potential tumor biomarkers present in body fluids, and abnormal glycosylation of saliva or lung glycoproteins. We further explored the effect of glycosylation changes on tumor signal transduction, and emphasized the role of receptor tyrosine kinases in tumorigenesis and metastasis.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/e1/main.PMC8718573.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simvastatin ameliorates oxidative stress levels in HepG2 cells and hyperlipidemic rats","authors":"Kanika Verma ,&nbsp;Shikha Makwana ,&nbsp;Sarvesh Paliwal ,&nbsp;Vartika Paliwal ,&nbsp;Smita Jain ,&nbsp;Swati Paliwal ,&nbsp;Swapnil Sharma","doi":"10.1016/j.crphar.2022.100088","DOIUrl":"10.1016/j.crphar.2022.100088","url":null,"abstract":"<div><p>Simvastatin is an established anti-hyperlipidemic drug and few studies have indicated its role in the mitigation of oxidative stress. However, a systematic study considering molecular binding/interaction of simvastatin with anti-oxidant enzymes followed by confirmational <em>in vitro</em> and <em>in vivo</em> studies have never been done. We investigated the molecular binding of simvastatin with multiple anti-oxidant enzymes and assessed their levels after the treatment of simvastatin <em>in vitro</em> and <em>in vivo</em>. This study is the first to show the molecular binding of simvastatin to catalase through molecular docking analysis. Moreover, the anti-oxidative properties of simvastatin have not been studied in Lipopolysaccharide (LPS) induced oxidative stress in HepG2 cells. We found that simvastatin effectively attenuated oxidative stress in LPS induced HepG2 cells and high-fat diet (HFD) fed hyperlipidemic rats by increasing the levels of antioxidant enzymes. The activity of catalase and superoxide dismutase (SOD) both increased significantly in oxidatively stressed HepG2 cells after the treatment with simvastatin (10 ​μM, 24 ​h). In addition to this, he original cell morphology of oxidatively stressed cells was restored by simvastatin, and an increase in antioxidant enzymes, catalase (0.08 U/cells to 0.12 U/cells), and SOD (0.57 U/cells to 0.74 U/cells) was also noted in HepG2 cells. Furthermore, a significant increase in the antioxidant enzymes such as Catalase, SOD, and reduced glutathione (GSH) was noted after simvastatin treatment in the HFD model. Moreover, we also observed degradation of by-products of lipid peroxidation thiobarbituric acid reactive substances (TBARs), nitric oxide (NO), and protein carbonyl levels. This indicates that simvastatin enhances anti-oxidant enzyme activities and can be repurposed for the treatment of oxidative stress in liver diseases in humans after extensive clinical trials.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100088"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/11/main.PMC8818901.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39908762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacodynamic evaluation of the XOR inhibitor WN1703 in a model of chronic hyperuricemia in rats induced by yeast extract combined with potassium oxonate","authors":"Yuanyuan Li ,&nbsp;Xinying Zhu ,&nbsp;Fuyao Liu,&nbsp;Wen Peng,&nbsp;Lei Zhang,&nbsp;Jing Li","doi":"10.1016/j.crphar.2022.100098","DOIUrl":"10.1016/j.crphar.2022.100098","url":null,"abstract":"<div><p>Hyperuricemia is a common disease caused by a disorder of purine metabolism, which often causes hyperlipidemia and other metabolic diseases. WN1703 was demonstrated to be an effective xanthine oxidoreductase (XOR) inhibitor in our previous study. Here, we evaluated the pharmacodynamic effect of WN1703 on rats suffering from chronic hyperuricemia accompanied by disorders of lipid metabolism. We discovered that WN1703 was an efficacious uric acid (UA)-lowering compound. Simultaneously, it had effect on relieving renal injury, regulating lipid metabolism by reducing levels of triglycerides and low-density lipoprotein-cholesterol, increasing levels of high-density lipoprotein-cholesterol, and improving renal and liver lesions. WN1703 also exhibited anti-inflammatory and antioxidant activity by alleviating the increasing trend of levels of tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, and malondialdehyde, and improving the activity of superoxide dismutase and glutathione peroxidase. WN1703 appeared to be more effective than febuxostat in inhibiting XOR and had higher antioxidant activity. In general, the pharmacologic action of WN1703 showed a clear dose–effect relationship.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100098"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000189/pdfft?md5=7953d7503a72979fce77444ba6a602aa&pid=1-s2.0-S2590257122000189-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45609166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalation potential of N-Acetylcysteine loaded PLGA nanoparticles for the management of tuberculosis: In vitro lung deposition and efficacy studies","authors":"Vishal Puri ,&nbsp;Kabi Raj Chaudhary ,&nbsp;Arti Singh ,&nbsp;Charan Singh","doi":"10.1016/j.crphar.2022.100084","DOIUrl":"https://doi.org/10.1016/j.crphar.2022.100084","url":null,"abstract":"<div><p>Several studies have stated that mucus is a critical hurdle for drug delivery to the mucosal tissues. As a result, Polymeric nanoparticles that can overcome mucus barriers are gaining popularity for controlled drug delivery into intra-macrophages to attain high intracellular drug concentration. The present study was aimed to fabricate inhalable N-acetylcysteine (NAC) modified PLGA mucus penetrating particles using the double emulsion method (w/o/w) for target delivery to alveolar macrophages and minimize the dose-related adverse effects, efficiently encapsulate hydrophilic drug, sustain the release profile and prolong the retention time for the management of tuberculosis. Among the numerous formulations, the drug/polymer ratio of 1:10 with 0.50% PVA concentration and sonication time for 2 ​min ​s was chosen for further research. The formulated nanoparticles had a mean particle size of 307.50 ​± ​9.54 ​nm, PDI was 0.136 ​± ​0.02, zeta potential about −11.3 ​± ​0.4 ​mV, decent entrapment efficiency (55.46 ​± ​2.40%), drug loading (9.05 ​± ​0.22%), and excellent flowability. FTIR confirmed that NAC and PLGA were compatible with each other. SEM graphs elucidated that the nanoparticles were spherically shaped with a slightly rough surface whereas TEM analysis ensured the nanometer size nanoparticles and coating of lipid over NPs surface. PXRD spectrum concluded the transformation of the drug from crystalline to amorphous state in the formulation. <em>In vitro</em> release pattern was biphasic started with burst release (64.67 ​± ​1.53% within 12hrs) followed by sustained release over 48hrs thus enabling the prolonged replenishing of NAC. <em>In vitro</em> lung deposition study pronounced that coated NAC-PLGA-MPPs showed favorable results in terms of emitted dose (86.67 ​± ​2.52%), MMAD value (2.57 ​± ​0.12 ​μm), GSD value (1.55 ​± ​0.11 ​μm), and FPF of 62.67 ​± ​2.08% for the deposition and targeting the lungs. Finally, <em>in vitro</em> efficacy studies demonstrated that NAC-PLGA-MPPs presented more prominent antibacterial activity against <em>MTB</em> H37Rv strain as compared to NAC. Hence, PLGA based particles could be a better strategy to deliver the NAC for lung targeting.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"3 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590257122000049/pdfft?md5=9d6ce61748d75bd93ac5b28f8736af54&pid=1-s2.0-S2590257122000049-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91588968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}