Treating Lymphangioleiomyomatosis with Inhaled Rapamycin Solid Lipid Nanoparticles
Emelie Land1, Lyn M. Moir1, Daniela Traini, Paul M. Young1 & Hui Xin Ong1
1Respiratory Technology, Woolcock Institute of Medical Research and
Faculty of Medicine and Health
The University of Sydney
NSW, 2037, Australia
Summary
Lymphangioleiomyomatosis (LAM) is a rare lung disease characterised by uncontrolled growth of smooth muscle cells in the lungs that can spread via the lymphatic system to other parts of the body. The current treatment of LAM is oral Rapamycin that is limited by its low oral bioavailability and side effects. Therefore, high-doses of rapamycin are required to achieve therapeutic doses to treat LAM in the lung and prevent its spread through the lymphatic system. The aim of this study is to develop an inhaled formulation of rapamycin solid lipid nanoparticles (SLNs) that will help the drug to by pass first -pass metabolism, increase its in-vivo half-life and facilitates entry into the lymphatic system through the lungs, thereby overcoming the problems associated with current oral treatment. Rapamycin and lipids for SLN were manufactured using a hot evaporation technique, before being freeze-dried overnight with 5% (w/v) mannitol. Particle characteristics were assessed using a Zetasizer and transmission electron microscope. The formulation’s in vitro aerosol performance was also evaluated using the next generation impactor (NGI) and in vitro release profile analysed via a dialysis bag experiment. The SLNs had an average particle size of 237.5±1.8nm (PDI=0.341), negative charge (-11.16) and high encapsulation efficiency (97.32 ±1.28%). The Fine Particle Fraction (FPF) and Mass Median Aerodynamic diameter (MMAD) was 44.127±5.1% and 5.317±0.38μm, respectively. This study successfully produced an inhaled formulation of rapamycin SLNs with the appropriate size, charge, in-vitro release performance and sustained release profile, making it suitable for pulmonary delivery and entry into the lymphatic system. This formulation is therefore a promising alternative treatment for LAM patients, as it could potentially reduce problems associated with low bioavailability and unpleasant side effects of current oral treatment.