Nano-embedded microparticles based dry powder inhaler for lung cancer treatment

Abstract

Lower efficacy of chemotherapeutic agents through the systemic route for treatment of lung cancer isattributed to its lower concentration in the lungs. Conversely, higher concentrations of drug in the lungs can beachieved by pulmonary administration via the inhalation route. For effective deposition of the formulation at thetarget region (small airways and alveoli) of the lung, the aerodynamic diameter has to be controlled (1-5 µm) and itsretention is of key importance. The present study attempted to design a dry powder inhalation formulation withcombined benefits of micron- and nano-sized particles [nano-embedded microparticles (NEMs)], which uponredispersion, results in nanoparticles (NPs) exhibiting good retention in the lungs. The present attempt is the foremostone to utilize NEMs administered by pulmonary route for the treatment of lung cancer. Docetaxel (DTX) NPs wasformulated using sonication solvent evaporation technique and characterized. Thereafter, DTX-NPs were embeddedinto microparticles using the spray drying technique. The NEMs exhibited the desired flow properties with Carr’sindex 10.18±2.79 and Hausner ratio 1.11±0.034. The mass median aerodynamic diameter was 3.74±0.11 µm and thefine particle fraction 42.96±1.66%. Redispersed NP fraction was 47.78±4.65% with NPs retaining the desiredproperties. NPs demonstrated a sustained release of upto 144 h. The particle size and PDI of the redispersed NPs wereunaffected. NEMs displayed stability upon charging under accelerated conditions for upto 3 months. Comparison ofthe cytotoxicity of DTX and DTX-NEMs revealed that the DTX-NEMs had more cytoxicity owing to the increaseduptake of liberated NPs by cells. The prepared formulation could successfully entrap NPs (with mucus barrierevading properties) in lactose microparticles, which can be deposited in the lungs and eventually, disintegrate to giveback NPs under simulated lung conditions. The results suggest that the developed NEMs can be used in inhaledchemotherapy for the treatment of non-small cell lung cancer.