Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles

Marianne Gauthier; Qian Yin; Jianjun Cheng; William D O'Brien Jr

doi:10.7863/ultra.34.8.1363

Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles

J Ultrasound Med. 2015 Aug;34(8):1363-72. doi: 10.7863/ultra.34.8.1363.

Authors

Marianne Gauthier¹, Qian Yin², Jianjun Cheng², William D O'Brien Jr²

Affiliations

¹ 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.
² 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.

Abstract

Objectives: 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.

Keywords: fluorescence; functionalized nanoparticles; microbubbles; stability.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Coated Materials, Biocompatible / chemical synthesis*
Coated Materials, Biocompatible / radiation effects
Delayed-Action Preparations / chemistry*
Delayed-Action Preparations / radiation effects
Drug Design
Materials Testing
Microbubbles
Nanocapsules / administration & dosage
Nanocapsules / chemistry*
Nanocapsules / radiation effects
Polyesters / chemistry*
Serum Albumin / chemistry*
Serum Albumin / radiation effects
Sonication / methods*
Ultrasonic Waves

Substances

Coated Materials, Biocompatible
Delayed-Action Preparations
Nanocapsules
Polyesters
Serum Albumin
poly(lactide)

Abstract

Publication types

MeSH terms

Substances

Grants and funding