PLGA Porous Microspheres Dry Powders for Codelivery of Afatinib‐Loaded Solid Lipid Nanoparticles and Paclitaxel: Novel Therapy for EGFR Tyrosine Kinase Inhibitors Resistant Nonsmall Cell Lung Cancer

Abstract

Combination therapy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR TKIs) with other chemotherapeutic agents is a feasible strategy to overcome resistance that often occurs after 9–13 months of EGFR TKIs administration in nonsmall cell lung cancer (NSCLC). In this study, a pulmonary microspheres system that codelivers afatinib and paclitaxel (PTX) is developed for treatment of EGFR TKIs resistant NSCLC. In this system, afatinib is loaded in stearic acid‐based solid lipid nanoparticles, then these nanoparticles and PTX are loaded in poly‐lactide‐co‐glycolide‐based porous microspheres. These inhaled microspheres systems are characterized including geometric particle size, drug encapsulation efficiency, morphology by scanning electron microscopy, specific surface area, in vitro drug release, and aerodynamic particle size. Cell experiments indicate that afatinib and PTX have a synergistic effect and the codelivery system shows a superior treatment effect in drug‐resistant NSCLC cells. The biocompatibility, pharmacokinetic, and tissue distribution experiments in Sprague–Dawley rats show that afatinib and PTX in the system can maintain 96 h of high lung concentration but low concentration in other tissues, with acceptable safety. These results demonstrate that this system may be a prospective delivery strategy for drug combination treatment in cancers developing resistance, especially drug‐resistant lung cancer.

Recent applications and strategies in nanotechnology for lung diseases

“…The results of the study showed that AFT and PTX have a synergistic effect and show excellent therapeutic effects in drug-resistant NSCLC cells. In vivo experiments have shown that PTX and AFT can maintain high concentrations in the lungs for 96 h. This drug delivery strategy provides research directions for EGFR TKI-resistant lung cancer [81].…”

Pulmonary Delivery of Anticancer Drugs via Lipid-Based Nanocarriers for the Treatment of Lung Cancer: An Update

“…These inhaled microspheres systems are characterized with D ae , FPF, fine particle dose (FPD), and GSD of 3.26 and 3.25 µm, 23.04 and 24.07%, 41.01 and 59.66 µg, 2.26 and 2.32, as well as EE% 53–70.85% of afatinib and paclitaxel, respectively. These final formulations showed an initial in vitro drug release for paclitaxel (20%) and afatinib (30%), with extremely high retention (more than 65%) in the induction port (17.21 ± 0.22% for afatinib and 16.00 ± 1.52% for paclitaxel), and no interaction between drugs and carriers when characterized by FTIR and NMR spectroscopy [ 126 ]. On the cellular level, there was a significant synergistic effect between afatinib and paclitaxel and superior treatment capability of the final loaded microspheres for drug-resistant NSCLC on H1975 and PC9/G cells.…”

The future of dry powder inhaled therapy: Promising or discouraging for systemic disorders?

“…Large porous particles (LPPs), by virtue of their porosity, exhibit an aerodynamic diameter much smaller than their geometric size, facilitating excellent flowability and improved dispersion ( Edwards et al, 1997 ). For example, the emulsion evaporation method enables the production of light porous particles that display an improved flowability and deep lung deposition ( Yang et al, 2019 ). Therefore, LPPs are highly efficient in the delivery of inhaled therapeutics into the systemic circulation ( Zhang et al, 2018 ).…”