Nilesh Gupta1, Brijeshkumar Patel, Fakhrul Ahsan. 1. Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, Amarillo, Texas, 79106, USA.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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 4°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 ~6-8 fold increase in the half-life of fasudil was observed when encapsulated in NERs. CONCLUSION: This study suggests that nanoerythrosomes can be used as cell derived carriers for inhalational delivery of fasudil.
PURPOSE: 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. METHODS: 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. RESULTS: 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 4°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 ~6-8 fold increase in the half-life of fasudil was observed when encapsulated in NERs. CONCLUSION: This study suggests that nanoerythrosomes can be used as cell derived carriers for inhalational delivery of fasudil.
Authors: A Johansson; M Lundborg; C M Sköld; J Lundahl; G Tornling; A Eklund; P Camner Journal: Am J Respir Cell Mol Biol Date: 1997-05 Impact factor: 6.914
Authors: Bernadett Kolozsvári; Éva Bakó; Bálint Bécsi; Andrea Kiss; Ágnes Czikora; Attila Tóth; György Vámosi; Pál Gergely; Ferenc Erdődi Journal: Cardiovasc Res Date: 2012-08-06 Impact factor: 10.787