caa a22 4500 445312866 CHVBK 20180317142636.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s11095-010-0247-y doi (NATIONALLICENCE)springer-10.1007/s11095-010-0247-y Investigating the Effect of Polymeric Approaches on Circulation Time and Physical Properties of Nanobubbles [Elektronische Daten] [Lisa du Toit, Thirumala Govender, Viness Pillay, Yahya Choonara, Tetsuya Kodama] ABSTRACT: Purpose: 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. Methods: 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. Results: 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 (−20.62mV to −17.54mV) 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. Conclusions: 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. Springer Science+Business Media, LLC, 2010 hydrogel nationallicence layer-by-layer self-deposition nationallicence liposome nationallicence nanobubble nationallicence polymer nationallicence du Toit Lisa Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa aut Govender Thirumala School of Pharmacy and Pharmacology, University of KwaZulu Natal, Durban, South Africa aut Pillay Viness Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa aut Choonara Yahya Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa aut Kodama Tetsuya Graduate School of Biomedical Engineering, Tohoku University, 2-1 Seiryo-machi, Aoba, 980-7583, Sendai, Japan aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 494-504 0724-8741 28:3<494 2011 28 11095 https://doi.org/10.1007/s11095-010-0247-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0247-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- du Toit Lisa Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa aut NATIONALLICENCE 700 1- Govender Thirumala School of Pharmacy and Pharmacology, University of KwaZulu Natal, Durban, South Africa aut NATIONALLICENCE 700 1- Pillay Viness Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa aut NATIONALLICENCE 700 1- Choonara Yahya Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa aut NATIONALLICENCE 700 1- Kodama Tetsuya Graduate School of Biomedical Engineering, Tohoku University, 2-1 Seiryo-machi, Aoba, 980-7583, Sendai, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 494-504 0724-8741 28:3<494 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer