title: Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles.
abstract: OBJECTIVE
  A protocol was designed to produce albumin-coated microbubbles (MBs) loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug delivery studies.
  
  
  METHODS
  Microbubbles resulted from the sonication of 5% bovine serum albumin and 15% dextrose solution. Functionalized NPs were produced by mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates. Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs were produced and compared. Statistical evaluations were based on quantitative analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB fabrication): MB diameter using a circle detection routine based on the Hough transform, MB number density using a hemocytometer, and NP-loading yield based on MB counts from fluorescence and light microscopic images. Loading capacity of the albumin-coated MBs was evaluated by fluorescence.
  
  
  RESULTS
  Loaded MB sizes were stable over 6 days after production and were not significantly different from that of time-matched unloaded MBs. Number density evaluation showed that only 1/1 NP/MB volume ratio and unloaded MB number densities were stable over time, and that the 1/1 MB number density evaluated at each time point was not significantly different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had unstable number densities that were significantly different from that of unloaded MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP-loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested that the 1/1 MBs had a loading capacity of 3700 NPs/MB.
  
  
  CONCLUSIONS
  A protocol was developed to load albumin MBs with functionalized PLA NPs for further drug delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to produce stable loaded MBs with a loading capacity of 3700 NPs/MB.
authors.affiliation: Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering (M.G., W.D.O.), and Department of Materials Science and Engineering (Q.Y., J.C.), University of Illinois at Urbana-Champaign, Urbana, Illinois USA. frenchmg@illinois.edu.
authors.forename: Marianne
authors.initials: M
authors.lastname: Gauthier
authors.affiliation: Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering (M.G., W.D.O.), and Department of Materials Science and Engineering (Q.Y., J.C.), University of Illinois at Urbana-Champaign, Urbana, Illinois USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering (M.G., W.D.O.), and Department of Materials Science and Engineering (Q.Y., J.C.), University of Illinois at Urbana-Champaign, Urbana, Illinois USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Bioacoustics Research Laboratory, Department of Electrical and Computer Engineering (M.G., W.D.O.), and Department of Materials Science and Engineering (Q.Y., J.C.), University of Illinois at Urbana-Champaign, Urbana, Illinois USA.
authors.forename: William D
authors.initials: WD
authors.lastname: O'Brien
mesh_terms: D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis* / Q000528:radiation effects; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000528:radiation effects; D015195:Drug Design; D008422:Materials Testing; D045423:Microbubbles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000528:radiation effects; D011091:Polyesters / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry* / Q000528:radiation effects; D013010:Sonication / Q000379:methods*; D000069453:Ultrasonic Waves
chemical_list: D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011091:Polyesters; D012709:Serum Albumin; C033616:poly(lactide)
keywords: fluorescence; functionalized nanoparticles; microbubbles; stability