Nanoparticle loaded microbubbles utilizing PolySciTech mPEG-PLA, PLA-PEG-COOH, and PLA-Fluorescein developed

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable PLA based polymers. Recently, research at University of Illinois at Urbana-Champaign utilized these polymers to generate PLA nanoparticles and load these nanoparticles into albumin-coated microbubbles to aid delivery. Read more: Gauthier, Marianne, Qian Yin, Jianjun Cheng, and William D. O’Brien. "Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles." Journal of Ultrasound in Medicine 34, no. 8 (2015): 1363-1372. http://www.jultrasoundmed.org/content/34/8/1363.short

“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. Abreviations BSA-bovine serum albumin, CI-confidence interval, COOH-carboxylate, Cy5-cyanine 5, DMF-dimethylformamide, FITC-fluorescein isothiocyanate, MB-microbubble, PEG-polyethylene glycol, NP-nanoparticle, PLA-polylactide”