Properties of rapamycin solid lipid nanoparticles for lymphatic access through the lungs: part II: the effect of nanoparticle charge

Aim: Lymphangioleiomyomatosis is characterized by smooth muscle-like cells in the lungs that spread to other organs via lymphatic vessels. Oral rapamycin is restricted by low bioavailability approximately 15%. The aim of the present study is to systematically investigate the effect of inhaled rapamycin solid lipid nanoparticles (Rapa-SLN) surface charge on efficacy and penetration into the lymphatics. Materials & methods: Rapa-SLN formulations with different charge: neutral, positive and negative, were produced and assessed for their physicochemical particle characteristics and efficacy in vitro. Results: Negative Rapa-SLNs were significantly faster at entering the lymphatic endothelium and more potent at inhibiting lymphanigiogenesis compared with neutral and positive Rapa-SLNs. Conclusion: Negative Rapa-SLNs showed efficient lymphatic access and should therefore be investigated further as a treatment for targeting extrapulmonary lymphangioleiomyomatosis.