Nanoarchitectonics of PLGA based polymeric nanoparticles with oseltamivir phosphate for lung cancer therapy: In vitro-in vivo evaluation

Oseltamivir phosphate (OSE) is an antiviral drug that also can inhibit tumor vascularization, growth and metastasis. The target of the present research was the delivery of OSE into the lung adenocarcinoma cells by means of developing nanosized, biocompatible and stealth nanoarchitectonics of pegylated PLGA NPs. For this goal, OSE encapsulated nanoarchitectonics of pegylated PLGA NPs were formulated and investigated for zeta potential, particle size, encapsulation efficiency, DSC, FT-IR, 1H-NMR and SEM analyses. In vitro release, cytotoxicity, determination of apoptotic pathways and in vivo CAM assay were carried out. NPs exhibited smaller particle size, relatively higher EE%, spherical shape, amorphous matrix formation and biphasic prolonged release pattern (fitted Peppas-Sahlin and Weibull model). All NPs was found as 103 times more effective than OSE on cancerous cells. Flow cytometry was employed to evaluate the apoptotic pathways using the Annexin V-FITC/PI, FITC Active Caspase-3 staining assay and mitochondrial membrane potential determination tests. Activations on caspase-3 pathways made us think that OSE loaded pegylated PLGA NPs triggered to apoptosis using intrinsic pathway. Upon in vivo studies, PLGA-OSE 3 demonstrated moderate antiangiogenic activity. These results indicate that OSE loaded PLGA NPs (especially PLGA-OSE 3) were chosen as a promising candidate and a potent formulation to treat lung cancer. [Display omitted] •This is the first report on the in vivo antiangiogenic investigation of nanoarchitectonics of OSE loaded PEG decorated PLGA nanoparticles using the in vitro FITC Active Caspase-3, Annexin V-FITC/PI staining and Mitochondrial Membrane Potential Detection on adenocarcinomic human alveolar basal epithelial cells (A549) and human lung fibroblast normal cells (CCD-19Lu) and in vivo CAM assay that alternative method for animal tests.•This is the first report on nanoarchitectonics of OSE loaded PEG modified PLGA nanoparticles for treatment of lung cancer with spray drying, characterization, in vitro release and release kinetics.•The most important characteristic of all of these is that the final pharmaceutical drug delivery system prepared is used at lower dose with moderate antiangiogenic activity relative to the pure OSE. This research would likely shed light on the use of nanoarchitectonics of OSE-loaded pegylated PLGA NPs how used to be an anticancer drug delivery system.