Multifunctional curcumin-loaded nanocarriers for lung delivery

Background: The severity of lung cancer and post-chemotherapy side effects are long-standing obstacles for treating the disease. Hence, developing targeted nanocarriers is a promising approach offering enhanced localized therapeutic action of anticancer agents delivered via a non-invasive inhalation route. In this study, four novel multifunctional nanocarriers were investigated as inhalation aerosols using polymers [hyaluronic acid (HA), Pluronic, chitosan (CS)] to enhance the pulmonary delivery of curcumin. Methods: The self-assembled curcumin-loaded Pluronic micelles with polymer coating were developed by thin-film hydration method. Polymeric conjugations were carried out to develop nanocarriers which were characterised for particle size distribution, surface charge, encapsulation efficiency and morphology. Spray dried dry powder inhalations (DPIs) and formulations for nebulisation were developed. In vitro aerosol characterisation was performed with a Next Generation Impactor (NGI) for DPIs delivered from a Cyclohaler® and for nebulised formulations delivered from a PARI LC® jet Sprint nebuliser using a twin stage impinger (TSI). Results: Pluronic-chitosan (PF68-CS), folic acid-chitosan (FA-CS), and Pluronic-curcumin conjugates were synthesised to produce distinct nanocarrier systems that improved curcumin aqueous solubility. Successful conjugation of the polymers and drug was confirmed using Fourier transform infra-red (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Enhanced encapsulation efficiency of the micelles (50-80%), and the presence of spherical shaped nanocarriers (< 500 nm) was observed in all developed formulations. A negative zeta potential confirmed the presence of HA on the surface of the micelles. A high fine particle fraction (FPF) (50-85%), and mass median aerodynamic diameter (MMAD) (2-5 µm) was observed. DPIs developed using dispersibility enhancers showed improved aerodynamic behaviour. The nebulised formulations improved fine particle dose of curcumin. Conclusions: Enhancement of curcumin solubility was achieved through nanocarriers, demonstrating that curcumin delivery to the lungs could be improved. The nanocarriers exhibited improved aerosol characteristics