DOE supported optimization of biodegradable polymeric nanoparticles based dry powder inhaler for targeted delivery of afatinib in non-small cell lung cancer

Abstract

Poly (lactic-co-glycolic acid) (PLGA) based nanoparticles are increasingly being used to deliver anticancer agents directly to the lungs. This approach offers targeted delivery of the drug, which minimizes the risk of side effects associated with oral administration. Afatinib-loaded PLGA nanoparticles were fabricated with a double emulsification solvent evaporation method and optimized by a factorial design (32) approach. The optimized batch of afatinib-loaded polymeric nanoparticles exhibited suitable entrapment efficiency (78.15 ± 2.20% w/w), drug loading (3.90 ± 0.11% w/w), particle size (198.1 ± 3.5 nm), and zeta potential (−0.519 ± 0.197 mV). A dry powder-based inhaled drug delivery platform is rapid-acting, handy, and self-administered that is expected to enhance patient compliance. The lyophilization method was used to convert afatinib-loaded PLGA nanoparticles into dry powder form. The formulated afatinib-loaded PLGA nanoparticles dry powder inhaler (PLGA NDPI) demonstrated good flow properties with 77.86 ± 3.02% drug content and 6.883 ± 0.369 μm particle size distribution. With more than 85% of the dosage released from an inhaler device in the eight-stage cascade impactor through an in-vitro lung deposition investigation, the particles also proved their capacity to penetrate the deeper area of the lung. Further, the in-vitro drug release study demonstrated more than 80% drug release from PLGA NDPI at different pH of phosphate buffer solutions. A549 adenocarcinoma cell line cytotoxicity investigation revealed that PLGA NDPI has a stronger potential for suppressing tumour cell proliferation than pure drug solution. Fluorescein isothiocyanate (FITC) encapsulated afatinib PLGA NDPI formulation was more effectively absorbed intracellularly by adenocarcinoma cells than plain FITC dye. Taken together, the results suggest that, the formulated afatinib PLGA NDPI can be a promising approach for targeted lung delivery of the anticancer agent.