Investigating the Effect of Polymeric Approaches on Circulation Time and Physical Properties of Nanobubbles
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A challenge in the field of nanobubbles, including lipobubbles and polymeric nanobubbles, is identification of formulation approaches to enhance circulation time or “bubble life” in the specific organ to allow for organ visualization. The aim of this study was to investigate the potential of two specific preparation approaches, polymeric surface modification to lipobubbles and a one-step approach for the preparation of ionotropically originated polymeric hydrogel nanobubbles for the production of biocompatible, biodegradable, and sufficiently echogenic (‘flexible’) bubbles, preferably within the nanometer range, that possess an enhanced in vivo lifetime compared to an unmodified lipobubble to allow visualization of the lymph node vasculature.
In the first approach, formed liposomes (basic and polymerically enhanced) were sequentially layered with appropriate cationic and anionic polyelectrolytes followed by transformation into polymer-coated nanobubbles. In addition, a one-step approach was employed for the fabrication of ionotropically originated polymeric hydrogel bubbles.
Bubble lifetime was marginally enhanced by self-deposition of polyelectrolytes onto the normal lipobubble, however, not significantly (P = 0.0634). In general, formulations possessing a higher ratio of anionic:cationic coats and highly anionic overall surface charge (−20.62 mV to −17.54 mV) possessed an enhanced lifetime. The improvement in bubble lifetime was significant when a purely polymeric polyionic hydrogel bubble shell was instituted compared to a normal unmodified lipobubble (P = 0.004). There was enhanced persistence of these systems compared to lipobubbles, attributed to the highly flexible, interconnected hydrogel shell which minimized gas leakage. The prolonged contrast signal may also be attributed to a degree of polymeric deposition/endothelial attachment.
This study identified the relevance of polymeric modifications to nanobubbles for an improved circulating lifetime, which would be essential for application of these systems in passive drug or gene targeting via the enhanced permeability and retention effect.
KEY WORDShydrogel layer-by-layer self-deposition liposome nanobubble polymer
This research was funded by the Asia-Africa Program, Tohoku University, Goho Life Sciences International Fund, and National Research Foundation of South Africa.
- 14.Cohen S, Andrianov AK, Wheatley M, Allcock HR, Langer RS. Gas-filled polymeric microbubbles for ultrasound imaging. United States Patent 5487390, 1996.Google Scholar
- 21.Murphy ED, Roths JB. Autoimmunity and lymphoproliferation: induction by mutant gene lpr, and acceleration by a male-associated factor in strain BXSB mice. New York: Elsevier North Holland Inc.; 1978.Google Scholar
- 22.O’ Doherty M. Liposome literature review. Nanobiotechnology and Bioanalysis Group, 2004.Google Scholar
- 25.Saxena V, Sadoqi M, Kumar S, Shao J. Tiny Bubbles—Multifunctional nanoparticles promise early noninvasive tumor detection and tumor destruction within the body. Nanotechnology. Oemagazine, September 2004. http://spie.org/x16543.xml?ArticleID=x16543.
- 28.Fisher NG, Christiansen J, Leong-Poi H, Jayaweera AR, Lindner JR, Kaul S. Myocardial and microcirculatory kinetics of BR-14, a novel third generation intravenous contrast agent. J Am Coll Cardiol. 2002;39:930–7.Google Scholar
- 29.Jin M, Zheng Y, Hu Q. Preparation and characterization of bovine serum albumin alginate/chitosan microspheres for oral administration. Asian J Pharm Sci. 2009;4:215–20.Google Scholar