David Encinas-Basurto1, Kiley McCombs 1, Ernest Vallorz1 & Heidi Mansour1,2
1 Skaggs Pharmaceutical Sciences Center, College of Pharmacy, The University of Arizona, 1703 E. Mabel St, Tucson, Arizona 85721, USA.
2 Department of Medicine, Division of Translational and Regenerative Medicine, The University of Arizona College of Medicine, Tucson, AZ, USA
Summary
In this study, novel biodegradable cross-linked carboxymethyl chitosan (CMC) nano/microgels were developed and evaluated in vitro as potential carriers for sustained pulmonary suramin salt (Sur) delivery. Upon deposition, aerosols must first go through efficient aerodynamic filtration to reach the deep lung, where they must then avoid rapid macrophage clearance to grant a local sustained release. Therefore, developing swellable nano/microparticles with respirable aerodynamic diameters in a dry state but larger geometric size via swelling is a promising approach to avoid alveolar macrophage clearance and achieve high deposition. This study designed nano/microgels by spray-drying CMC for suramin salt delivery with L-Leucine (Leu) as an aerosolize enhancer molecule. Particle size distribution, in vitro lung deposition, and in vitro release profile were tested in each formulation. NGI parameters showed satisfactory aerosol properties for inhalation, with fine particle fraction (FPF) over 30%, a respirable fraction (% RF) over 80 %, and MMAD as low as 1 µm. In addition, in vitro dissolution test of nano/microgels exhibited sustained Sur for more than 48 h with swelled particles.
Key Message
The addition of Leu into CMC nano/microgels shows suitable properties to be used for dry powder inhalation targeting deep lung for sustain release of suramin salt and once swell, escape from macrophages clearance.