Electrosprayed dry powder formulations of paclitaxel/carboplatin for the treatment of non-small cell lung cancer

Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for about 85% of all cases. Current emerging treatment options still show limited clinical benefit, making chemotherapy an important part of NSCLC management. Although multiple clinical trials have demonstrated the efficacy of carboplatin combined with paclitaxel in patients with NSCLC, adverse reactions and safety concerns associated with traditional chemotherapy administration remain significant, highlighting the need for alternative drug delivery strategies. Pulmonary drug delivery enables direct drug deposition in the lungs with reduced systemic exposure. Dry powder formulations provide an alternative to liquid aerosol systems for pulmonary drug delivery, with electrospraying offering a flexible approach for preparing inhalable dry powder particles. In this study, electrosprayed particles based on polyvinyl alcohol (PVA) and chitosan were developed and optimised for the pulmonary delivery of paclitaxel and carboplatin. The particles were characterised using electron microscopy, laser diffraction, and next-generation impactor, and their biological performance was evaluated in A549 and Calu-3 cells. Despite a primary particle size below 1 μm, particle aggregation led to volumetric and aerodynamic diameters within the optimal range (1-5 μm) for pulmonary deposition. The formulations showed low moisture content (<3% w/w) with good aerosol performance, achieving over 80% emitted dose and the highest effective fine particle fraction of 58.61 ± 0.83%. Both drugs were successfully encapsulated with a rapid release of 70-90% within the first 2 h. Chitosan coating increased particle adhesion and cell interaction, and cell viability studies confirmed cytotoxic effects against A549 cells over 72 h.