Nano-Engineered Erythrocyte Ghosts as Inhalational Carriers for Delivery of Fasudil: Preparation and Characterization

Nanoerythrosomes (NERs), an engineered derivative of erythrocytes, have long been used as drug delivery carriers. These cell based carriers are biocompatible and biodegradable, and they exhibit efficient drug loading, targeting specificity and prolonged biological half-life. In this study, we have evaluated the feasibility of NERs as inhalable carriers for delivery of fasudil, an investigational drug for the treatment of pulmonary arterial hypertension. We prepared NERs by hypotonic lysis of erythrocytes derived from rat blood followed by extrusion through polycarbonate membranes. The formulations were optimized and characterized for size, morphology, entrapment efficiency, stability, cellular uptake and in-vitro release profiles followed by monitoring of drug absorption and safety evaluation after intratracheal administration of fasudil-loaded NERs into rats. NERs were spherical in shape with an average size of 154.1 +/- 1.31 nm and the drug loading efficiency was 48.76 +/- 2.18%. Formulations were stable when stored at 4A degrees C for 3 weeks. When incubated with rat pulmonary arterial smooth muscle cells (PASM), a significant amount of NERs was taken up by PASM cells. The drug encapsulated in NERs inhibited the rho-kinase activity upto 50%, which was comparable with the plain fasudil. A similar to 6-8 fold increase in the half-life of fasudil was observed when encapsulated in NERs. This study suggests that nanoerythrosomes can be used as cell derived carriers for inhalational delivery of fasudil.