title: Cell permeable peptide conjugated nanoerythrosomes of fasudil prolong  pulmonary arterial vasodilation in PAH rats.
abstract: In this study, we tested the hypothesis that a cell permeable peptide, CARSKNKDC (CAR), conjugated nanoerythrosomes (NERs) containing fasudil, a rho-kinase (ROCK) inhibitor, produces prolonged pulmonary preferential vasodilation. CAR conjugated NERs containing fasudil were prepared by hypotonic lysis and extrusion method, and optimized for various physicochemical properties in-vitro. The formulations were then used to study the hemodynamic efficacy in a monocrotaline-induced rodent model of pulmonary arterial hypertension (PAH). CAR-NERs-Fasudil was spherical in shape with an average vesicle size and entrapment efficiency of 161.3 ± 1.37 nm and 48.81 ± 1.96%, respectively. Formulations were stable for ~3 weeks when stored at 4 °C and the drug was released in a controlled fashion for >48 h. The uptake of CAR-NERs-Fasudil by TGF-b activated pulmonary arterial smooth muscle cell was ~1.5-fold greater than the uptake of NERs-Fasudil. CAR-NERs-Fasudil inhibited ROCK activity and 5-hydroxytryptamine induced cell proliferation. In terms of reduction of pulmonary arterial pressure, intratracheal administration of CAR-NERs-Fasudil was ~2-fold more specific to the lungs compared with plain fasudil. Overall,CAR peptide grafted nanoerythrosomes offers a new platform for improving the therapeutic efficacy ofa rho-kinase inhibitor, fasudil, without affecting peripheral vasodilation.
authors.forename: Nilesh
authors.initials: N
authors.lastname: Gupta
authors.forename: Brijeshkumar
authors.initials: B
authors.lastname: Patel
authors.forename: Kamrun
authors.initials: K
authors.lastname: Nahar
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Ahsan
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism; D011510:Proteolipids / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004337:Drug Carriers; D010455:Peptides; D011510:Proteolipids; C020485:proteoliposomes; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C049347:fasudil