title: A needleless liquid jet injection delivery method for cardiac gene therapy: a comparative evaluation versus standard routes of delivery reveals enhanced therapeutic retention and cardiac specific gene expression.
abstract: This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n = 24 rats), retention of dye was evaluated 10 min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52 ± 4] % and LVIC-OCCL [58 ± 3] % groups p < 0.05 compared with IM [31 ± 8] % and LVIC [35 ± 4] %. In the second (n = 16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6 weeks post-delivery, a similar trend was found with liquid jet [54 ± 5] % and LVIC-OCCL [60 ± 8] % featuring more LV expression as compared with IM [30 ± 9] % and LVIC [23 ± 9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.
authors.affiliation: Sanger Heart & Vascular Institute, Thoracic and Cardiac Surgery, Cannon Research Center, Carolinas Healthcare System, 1542 Garden Terrace, Charlotte, NC, 28203, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Fargnoli
authors.forename: M G
authors.initials: MG
authors.lastname: Katz
authors.forename: R D
authors.initials: RD
authors.lastname: Williams
authors.forename: K B
authors.initials: KB
authors.lastname: Margulies
authors.forename: Charles R
authors.initials: CR
authors.lastname: Bridges
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D004867:Equipment Design; D005355:Fibrosis; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000378:metabolism; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques / Q000295:instrumentation*; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D007263:Infusions, Parenteral; D007273:Injections, Intramuscular; D008297:Male; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000008:administration & dosage / Q000378:metabolism; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; D012235:Rhodamines; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C029773:rhodamine B