A Controlled Antibiotic Release System for the Development of Single-Application Otitis Externa Therapeutics
"> Figure 1
<p>Tetraethyl orthosilicate (TEOS) hydrolysis. (<b>A</b>) Reaction scheme for the formation of the SiO<sub>2</sub> network due to TEOS hydrolysis; (<b>B</b>) Fourier-transformed infrared spectroscopy (FTIR) monitoring of TEOS hydrolysis indicating the apparition of the ethanol peak—a side product of the TEOS hydrolysis reaction; and (<b>C</b>) Proton nuclear magnetic resonance (<sup>1</sup>H-NMR) analysis and confirmation of TEOS hydrolysis. The upper spectrum corresponds to TEOS, while the bottom spectrum shows a shift in the –CH<sub>2</sub>– (methylene) peak from 3.8 to 3.4 ppm and –CH<sub>3</sub> (methyl) peak from 1.1 to 0.9 ppm, indicative of hydrolysis. The 2.0 ppm peak in the hydrolyzed TEOS spectrum corresponds to the methyl groups of the acetic acid used for hydrolysis.</p> "> Figure 2
<p>Physical appearance and optical clarity of thixogels.</p> "> Figure 3
<p>Rheological evaluation of hydrogel thixotropy during three stress cycles. All three formulations show stress-dependent gel-sol transitions. After the first cycle, for all formulations, the storage modulus (G′) values were higher, most likely due to polymeric network consolidation through solvent exclusion.</p> "> Figure 4
<p>Evaluation of the temperature dependent behavior of the thixogels. A slight temperature dependence (approximately 10% increase in G′) is observed at temperatures above 60 °C, probably due to solvent loss.</p> "> Figure 5
<p>Evaluation of the swelling behavior of thixogels in aqueous environments, indicating that the hydrogels minimally change their volumes (approximately 1%) in the presence of physiological fluids (no statistically significant differences were noted between the three formulations).</p> "> Figure 6
<p>Thixogels cytocompatibility assessment. (<b>A</b>) LIVE/DEAD evaluation of cells on TXH indicating the presence of active intracellular esterases, intact cell membranes and some cytoplasmic vacuolation (circled); (<b>B</b>) evaluation of cellular metabolic activity via methyl tetrazolium salt (MTS) Cell-Titer assay, indicating reduced mitochondrial activity on TXL and TXH; (<b>C</b>) improvement of cellular metabolic activity through the addition on polyethylene glycol, molecular weight 600 Da (PEG600) to TXH; and (<b>D</b>) LIVE/DEAD evaluation of cells on TXH/PEG600 75% showing a more physiological spindle-like morphology with some cytoplasmic vacuolation (circled).</p> "> Figure 7
<p>Evaluation of the controlled release capabilities of the thixogels by using fluorescein as a model drug. Lanolin—a compounding wax used for otic ointments—was used as a control. All three thixogels elicited controlled release properties for seven days.</p> "> Figure 8
<p>Fluorescein release from thixogels indicating the controlled release capabilities of the hydrogels. (<b>A</b>) Evaluation of the effects of PEG200 addition, in different amounts, on the fluorescein release properties, compared to TXH; (<b>B</b>) evaluation of the effects of PEG600 addition, in different amounts, on the fluorescein release properties, compared to TXH; (<b>C</b>) comparison of TXH, TXH + PEG200 50%, and TXH + PEG600 50% release rates indicating that longer PEG chains decrease the release rates; and (<b>D</b>) assessment of the loading capacity of the thixogels with four different concentrations of fluorescein, indicating a consistent loading efficiency of ~70%.</p> "> Figure 9
<p>Evaluation of the antibacterial activity of thixogels. (<b>A</b>) Evaluation of the effect of TEOS amounts (TXL versus TXH) on <span class="html-italic">S. aureus</span> growth; (<b>B</b>) evaluation of the effect of TEOS amounts (TXL versus TXH) on <span class="html-italic">P. aeruginosa</span> growth; (<b>C</b>) evaluation of TXH hydrogels with and without PEG on <span class="html-italic">S. aureus</span> growth; and (<b>D</b>) evaluation of TXH hydrogels with and without PEG on <span class="html-italic">P. aeruginosa</span> growth.</p> "> Figure 10
<p>Evaluation of thixogel dehydration rates indicating that all formulations would gradually dry out to a small amount of dry material, and most likely would be naturally eliminated without causing hearing impairment.</p> ">
Abstract
:1. Introduction
2. Results
2.1. Hydrogel Formation
2.2. Hydrogel Rheology
2.3. Cellular Effects of Hydrogels
2.4. Controlled Release Evaluation
2.5. Antibacterial Activity
2.6. Hydrogel Dehydration Rates
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Materials
5.2. Analytical Instrumentation
5.3. Gel Formation
5.4. Controlled Release
5.5. Rheological Characterization
5.6. Cell Assays
5.7. Bacterial Assays
5.8. Statistical Analysis
Acknowledgments
Author Contributions
Conflicts of Interest
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Hydrogel | Designation | Formulation |
---|---|---|
H2O:hTEOS (v/v) | ||
Thixogel—low density SiO2 network | TXL | 1:1 |
Thixogel—medium density SiO2 network | TXM | 1:1.5 |
Thixogel—high density SiO2 network | TXH | 1:2 |
Hydrogel | Volume Increase Due to Swelling (%) | Standard Deviation (%) |
---|---|---|
TXL | 0.90 | 0.10 |
TXM | 0.96 | 0.26 |
TXH | 0.67 | 0.40 |
Hydrogel | Dry Weight/100 μg Hydrogel (in μg) | Standard Deviation (μg) |
---|---|---|
TXL | 1.198 | 0.030 |
TXM | 1.196 | 0.005 |
TXH | 1.238 | 0.021 |
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Serban, B.A.; Stipe, K.T.; Alverson, J.B.; Johnston, E.R.; Priestley, N.D.; Serban, M.A. A Controlled Antibiotic Release System for the Development of Single-Application Otitis Externa Therapeutics. Gels 2017, 3, 19. https://doi.org/10.3390/gels3020019
Serban BA, Stipe KT, Alverson JB, Johnston ER, Priestley ND, Serban MA. A Controlled Antibiotic Release System for the Development of Single-Application Otitis Externa Therapeutics. Gels. 2017; 3(2):19. https://doi.org/10.3390/gels3020019
Chicago/Turabian StyleSerban, Bogdan A., Kristian T. Stipe, Jeremy B. Alverson, Erik R. Johnston, Nigel D. Priestley, and Monica A. Serban. 2017. "A Controlled Antibiotic Release System for the Development of Single-Application Otitis Externa Therapeutics" Gels 3, no. 2: 19. https://doi.org/10.3390/gels3020019
APA StyleSerban, B. A., Stipe, K. T., Alverson, J. B., Johnston, E. R., Priestley, N. D., & Serban, M. A. (2017). A Controlled Antibiotic Release System for the Development of Single-Application Otitis Externa Therapeutics. Gels, 3(2), 19. https://doi.org/10.3390/gels3020019