Traditional means to identify and treat arterial disease are hampered by their inability to direct therapeutics to local atheroma components. Novel targeted acoustic delivery agents (liposomes) with novel ultrasound delivery methodologies may overcome these problems. Liposomes are phospholipid vesicles enclosing an aqueous space. We have developed a unique methodology that, by process and composition, makes these liposomes echogenic. This formulation allows modification for antibody conjugation and therapeutic (drug/bioactive gas) incorporation. Work by our group has demonstrated that these formulations can incorporate and deliver therapeutics to cells, while retaining their echogenic properties. The latter is important as the addition of therapeutic ultrasound has a unique effect on these echogenic liposomes by increasing cellular delivery. Our principal aim is to develop a model carrier and a technique that has the ability to incorporate a therapeutic with delivery to a target structure while retaining the therapeutic?s effects. We have: a) developed robust therapeutic echogenic immunoliposomes (ELIP); b) developed ultrasound parameters for therapeutic delivery of loaded ELIP and c) determined the efficacy of our therapeutic ELIP in slowing/stabilizing atheroma progression. We will now translate our discoveries for use in unstable atheroma and translate them into the clinical setting. We will develop a novel ultrasound methodology for therapeutic delivery into the coronary arterial beds. We will evaluate our therapeutic-loaded carriers with ultrasound activation in vivo and translate our optimal strategy into the clinical setting. Development of these agents and techniques would have far reaching implications for the treatment of chronic high risk atherosclerosis.

Public Health Relevance

This proposal seeks to develop a carrier (echogenic immunoliposomes) with novel ultrasound delivery methodologies that have the ability to incorporate therapeutics and enhance delivery to stabilize atherosclerotic beds at the time of intervention.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL135092-01
Application #
9217206
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Danthi, Narasimhan
Project Start
2017-04-15
Project End
2022-03-31
Budget Start
2017-04-15
Budget End
2018-03-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77030