title: Investigating the effect of polymeric approaches on circulation time and physical properties of nanobubbles.
abstract: OBJECTIVE
  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 (-20.62 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.
  
  
  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.
authors.affiliation: Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193 Johannesburg, South Africa.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: du Toit
authors.forename: Thirumala
authors.initials: T
authors.lastname: Govender
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kodama
mesh_terms: D001776:Blood Circulation Time / Q000187:drug effects / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008081:Liposomes; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D008081:Liposomes; D004364:Pharmaceutical Preparations; D011108:Polymers