Ultrasonically Controlled Release of Ciprofloxacin from Self-Assembled Coatings on Poly(2-Hydroxyethyl Methacrylate) Hydrogels forPseudomonas aeruginosaBiofilm Prevention

Abstract

Indwelling prostheses and subcutaneous delivery devices are now routinely and indispensably employed in medical practice. However, these same devices often provide a highly suitable surface for bacterial adhesion and colonization, resulting in the formation of complex, differentiated, and structured communities known as biofilms. The University of Washington Engineered Biomaterials group has developed a novel drug delivery polymer matrix consisting of a poly(2-hydroxyethyl methacrylate) hydrogel coated with ordered methylene chains that form an ultrasound-responsive coating. This system was able to retain the drug ciprofloxacin inside the polymer in the absence of ultrasound but showed significant drug release when low-intensity ultrasound was applied. To assess the potential of this controlled drug delivery system for the targeting of infectious biofilms, we monitored the accumulation of Pseudomonas aeruginosa biofilms grown on hydrogels with and without ciprofloxacin and with and without exposure to ultrasound (a 43-kHz ultrasonic bath for 20 min daily) in an in vitro flow cell study. Biofilm accumulation from confocal images was quantified and statistically compared by using COMSTAT biofilm analysis software. Biofilm accumulation on ciprofloxacin-loaded hydrogels with ultrasound-induced drug delivery was significantly reduced compared to the accumulation of biofilms grown in control experiments. The results of these studies may ultimately facilitate the future development of medical devices sensitive to external ultrasonic impulses and capable of treating or preventing biofilm growth via "on-demand" drug release.

Effect of Delayed Pulsed-Wave Ultrasound on Local Pharmacokinetics and Pharmacodynamics of Vancomycin-Loaded Acrylic Bone Cement In Vivo

“…hips but without insonation, (ii) the normal ultrasound group (UG 0-12 ; n ϭ 10) with bilateral hips insonated from 0 through 12 h after surgery, and (iii) the delayed-ultrasound group (UG [12][13][14][15][16][17][18][19][20][21][22][23][24] ; n ϭ 10) with bilateral hips insonated from 12 through 24 h after surgery.…”

“…Vancomycin concentrations in left hips were measured at projected time intervals over 48 h. Viable bacteria in both right hip aspirates and right femoral tissues were counted at 48 h. Thereafter, a linear regression model was set up for the analysis of the correlation between bacterial survival in hip cavities and each PK/PD parameter or the synergism of ultrasound and vancomycin. In addition, volumes of drainage fluid from both hip cavities of rabbits from UG 0-12 (n ϭ 2) and UG [12][13][14][15][16][17][18][19][20][21][22][23][24] (n ϭ 2) during a 12-h insonation were measured and compared. The figure is not to scale.…”

“…Flow chart of the study. After the implantation of cement and the inoculation of S. aureus into hip cavities and femoral canals of both sides, ultrasound was applied to animals of UG 0-12 (n ϭ 10) from 0 through 12 h and to animals of UG [12][13][14][15][16][17][18][19][20][21][22][23][24] (n ϭ 10) from 12 through 24 h, whereas CG (n ϭ 8) was not exposed to ultrasound. Vancomycin concentrations in left hips were measured at projected time intervals over 48 h. Viable bacteria in both right hip aspirates and right femoral tissues were counted at 48 h. Thereafter, a linear regression model was set up for the analysis of the correlation between bacterial survival in hip cavities and each PK/PD parameter or the synergism of ultrasound and vancomycin.…”

Prevention and treatment of biofilms by hybrid- and nanotechnologies

“…64 Similarly, biofilm growth in ciprofloxacin-loaded hydrogels with US induced (43 kHz ultrasonic bath for 20 minutes daily) was significantly lower compared controls. 65 Clearly, augmenting antibiotic treatment with ultrasound is a promising device combination for drug delivery to counter biofilms.…”

Responsive Polymers for Crop Protection

“…The biodegradables include polyglycolides, polylactides, bis(p-carboxyphen-oxy) alkane anhydride with sebacic acid. The non-biodegradables include ethylene-vinyl acetate copolymers or the poly(lactide-co-glycolide) microspheres, PHEMA hydrogels, the PEO-b-PPO-b-PEO micelles and the poly(HEMA-co-DMAEMA) hydrogels [2][3][4][5][6][7][8]. An interesting report out-lines using perfluorcarbon gas-filled microbubbles, coated via the layer-by-layer (LbL) approach, with positively charged poly(allylamine hydrochloride) and negatively charged DNA.…”