Preparation Optimization And Characterization Of Nanocarriers Based Dry Powder Inhaler In The Treatment Of Non Small Cell Lung Cancer

Abstract

Pulmonary delivery of anticancer agents has progressively been studied as a potential newlineroute for site-specific delivery to the lungs. Rapid innovation in the area of newlinenanotechnology leads to the need for nanocarriers as delivery to become the subject newlineof dynamic research. The aim of the current project work is to develop a nanocarrier newlinebased dry powder inhaler of afatinib for the management of lung cancer by the newlineinhalation route. A dry powder-based inhaled drug delivery platform is rapid-acting, newlinehandy, and self-administered that is expected to enhance patient compliance. Afatinib newlineis a second-generation orally administered irreversible 4-anilino-quinazoline tyrosine newlinekinase family of EGFR inhibitors and is considered the primary therapy for patients newlinehaving metastatic non-small cell lung cancer. But, its application is restricted due to newlinedose-related serious adverse reactions like pneumonia, dermatitis, stomatitis, newlinedecreased appetite, diarrhea, dyspnea, and skin rashes. Additionally, higher newlinebinding specifically with hemoglobin, an endogenous protein, enhances the chances newlineof drug reactions. Thus, the present investigation utilized liposomes and polymeric newlinenanoparticles as nanocarriers for the targeted delivery of afatinib to lungs by the newlineinhalation route for the remedy of lung cancer. Afatinib-encapsulated polymeric newlinenanoparticles and liposomes were prepared by the double emulsification method and newlinethe ethanol injection method, respectively. Both formulations were optimized by a newlinefactorial design (3 newline 2 newline ) approach. Scale-up of afatinib-loaded liposomal and polymeric newlinenanoparticle dispersions were successfully executed and characterized for zeta newlinepotential (mV), particle size (nm), drug loading (%), and entrapment efficiency (%). newlineFurther, afatinib-loaded liposomal and polymeric dispersions were converted into dry newlineform by a validated lyophilization technique. Finally, the afatinib-loaded liposomal and newlinepolymeric nanoparticles based dry powder inhaler were characterized. The results newlineobtained indicated that t