Inhalable lung
surfactant-based carriers composed of synthetic
phospholipids,
dipalmitoylphosphatidylcholine (DPPC) and
dipalmitoylphosphatidylglycerol (
DPPG), along with
paclitaxel (PTX), were designed and optimized as respirable dry powders using organic
solution co-spray-drying particle engineering design. These materials can be used to deliver and treat a wide variety of
pulmonary diseases with this current work focusing on
lung cancer. In particular, this is the first time dry
powder lung
surfactant-based particles have been developed and characterized for this purpose. Comprehensive physicochemical characterization was carried out to analyze the particle morphology, surface structure, solid-state transitions, amorphous character, residual water content, and
phospholipid bilayer structure. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR) spectroscopy. PTX loading was high, as quantified using UV-VIS spectroscopy, and sustained PTX release was measured over weeks. In vitro cellular characterization on
lung cancer cells demonstrated the enhanced chemotherapeutic cytotoxic activity of
paclitaxel from co-spray-dried DPPC/
DPPG (co-SD DPPC/
DPPG) lung
surfactant-based carrier particles and the cytotoxicity of the particles via pulmonary cell viability analysis, fluorescent microscopy imaging, and transepithelial electrical resistance (TEER) testing at air-interface conditions. In vitro
aerosol performance using a Next Generation Impactor™ (NGI™) showed measurable
powder deposition on all stages of the NGI and was relatively high on the lower stages (nanometer aerodynamic size).
Aerosol dispersion analysis of these high-performing DPIs showed mass median diameters (MMADs) that ranged from 1.9 to 2.3 μm with excellent
aerosol dispersion performance as exemplified by high values of emitted dose, fine particle fractions, and respirable fractions.