{"title":"A nanotechnology driven effectual localized lung cancer targeting approaches using tyrosine kinases inhibitors: Recent progress, preclinical assessment, challenges, and future perspectives","authors":"","doi":"10.1016/j.ijpharm.2024.124745","DOIUrl":null,"url":null,"abstract":"<div><div>The higher incidence and mortality rate among all populations worldwide explains the unmet solutions in the treatment of lung cancer. The evolution of targeted therapies using tyrosine kinase inhibitors (TKI) has encouraged anticancer therapies. However, on-target and off-target effects and the development of drug resistance limited the anticancer potential of such targeted biologics. The advances in nanotechnology-driven-TKI embedded carriers that offered a new path toward lung cancer treatment. It is the inhalation route of administration known for its specific, precise, and efficient drug delivery to the lungs. The development of numerous TKI-nanocarriers through inhalation is proof of TKI growth. The future scopes involve using potential lung cancer biomarkers to achieve localized active cancer-targeting strategies. The adequate knowledge of <em>in vitro</em> absorption models usually helps establish better <em>in vitro − in vivo</em> correlation/extrapolation (IVIVC/E) to successfully evaluate inhalable drugs and drug products. The advanced <em>in vitro</em> and <em>ex vivo</em> lung tissue/ organ models offered better tumor heterogeneity, etiology, and microenvironment heterogeneity. The involvement of lung cancer organoids (LCOs), human organ chip models, and genetically modified mouse models (GEMMs) has resolved the challenges associated with conventional <em>in vitro</em> and <em>in vivo</em> models. To access potential inhalation-based drugtherapies, biological barriers, drug delivery, device-based challenges, and regulatory challenges must be encountered associated with their development. A proper understanding of material toxicity, size-based particle deposition at active disease sites, mucociliary clearance, phagocytosis, and the presence of enzymes and surfactants are required to achieve successful inhalational drug delivery (IDD). This article summarizes the future of lung cancer therapy using targeted drug-mediated inhalation using TKI.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378517324009797","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
The higher incidence and mortality rate among all populations worldwide explains the unmet solutions in the treatment of lung cancer. The evolution of targeted therapies using tyrosine kinase inhibitors (TKI) has encouraged anticancer therapies. However, on-target and off-target effects and the development of drug resistance limited the anticancer potential of such targeted biologics. The advances in nanotechnology-driven-TKI embedded carriers that offered a new path toward lung cancer treatment. It is the inhalation route of administration known for its specific, precise, and efficient drug delivery to the lungs. The development of numerous TKI-nanocarriers through inhalation is proof of TKI growth. The future scopes involve using potential lung cancer biomarkers to achieve localized active cancer-targeting strategies. The adequate knowledge of in vitro absorption models usually helps establish better in vitro − in vivo correlation/extrapolation (IVIVC/E) to successfully evaluate inhalable drugs and drug products. The advanced in vitro and ex vivo lung tissue/ organ models offered better tumor heterogeneity, etiology, and microenvironment heterogeneity. The involvement of lung cancer organoids (LCOs), human organ chip models, and genetically modified mouse models (GEMMs) has resolved the challenges associated with conventional in vitro and in vivo models. To access potential inhalation-based drugtherapies, biological barriers, drug delivery, device-based challenges, and regulatory challenges must be encountered associated with their development. A proper understanding of material toxicity, size-based particle deposition at active disease sites, mucociliary clearance, phagocytosis, and the presence of enzymes and surfactants are required to achieve successful inhalational drug delivery (IDD). This article summarizes the future of lung cancer therapy using targeted drug-mediated inhalation using TKI.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.