PURPOSE: To develop a safe and efficient gene delivery system into skeletal muscle using the combination of Bubble liposomes (BL) and ultrasound (US) exposure, and to assess the feasibility and the effectiveness of BL for angiogenic gene delivery in clinical use. METHODS: A solution of luciferase-expressing plasmid DNA (pDNA) and BL was injected into the tibialis (TA) muscle, and US was immediately applied to the injection site. The transfection efficiency was estimated by a luciferase assay. The ischemic hindlimb was also treated with BL and US-mediated intramuscular gene transfer of bFGF-expressing plasmid DNA. Capillary vessels were assessed using immunostaining. The blood flow was determined using a laser Doppler blood flow meter. RESULTS: Highly efficient gene transfer could be achieved in the muscle transfected with BLs, and US mediated the gene transfer. Capillary vessels were enhanced in the treatment groups with this gene transfer method. The blood flow in the treated groups with this gene transfer method quickly recovered compared to other treatment groups (non-treated, bFGF alone, or bFGF+US). CONCLUSION: The gene transfer system into skeletal muscle using the combination of BL and US exposure could be an effective means for angiogenic gene therapy in limb ischemia.
PURPOSE: To develop a safe and efficient gene delivery system into skeletal muscle using the combination of Bubble liposomes (BL) and ultrasound (US) exposure, and to assess the feasibility and the effectiveness of BL for angiogenic gene delivery in clinical use. METHODS: A solution of luciferase-expressing plasmid DNA (pDNA) and BL was injected into the tibialis (TA) muscle, and US was immediately applied to the injection site. The transfection efficiency was estimated by a luciferase assay. The ischemic hindlimb was also treated with BL and US-mediated intramuscular gene transfer of bFGF-expressing plasmid DNA. Capillary vessels were assessed using immunostaining. The blood flow was determined using a laser Doppler blood flow meter. RESULTS: Highly efficient gene transfer could be achieved in the muscle transfected with BLs, and US mediated the gene transfer. Capillary vessels were enhanced in the treatment groups with this gene transfer method. The blood flow in the treated groups with this gene transfer method quickly recovered compared to other treatment groups (non-treated, bFGF alone, or bFGF+US). CONCLUSION: The gene transfer system into skeletal muscle using the combination of BL and US exposure could be an effective means for angiogenic gene therapy in limb ischemia.
Authors: Peter Schratzberger; Joseph G Krainin; Gabriele Schratzberger; Marcy Silver; Hong Ma; Marianne Kearney; Robert F Zuk; Axel F Brisken; Douglas W Losordo; Jeffrey M Isner Journal: Mol Ther Date: 2002-11 Impact factor: 11.454
Authors: Evan C Unger; Thomas Porter; William Culp; Rachel Labell; Terry Matsunaga; Reena Zutshi Journal: Adv Drug Deliv Rev Date: 2004-05-07 Impact factor: 15.470
Authors: Rahul Nahire; Manas K Haldar; Shirshendu Paul; Anaas Mergoum; Avinash H Ambre; Kalpana S Katti; Kara N Gange; D K Srivastava; Kausik Sarkar; Sanku Mallik Journal: Biomacromolecules Date: 2013-02-20 Impact factor: 6.988