Levofloxacin HCl-Loaded Eudragit L-Based Solvent Exchange-Induced In Situ Forming Gel Using Monopropylene Glycol as a Solvent for Periodontitis Treatment
"> Figure 1
<p>Chemical structure of Eudragit<sup>®</sup> L and S 100 (<b>a</b>), monopropylene glycol (<b>b</b>), and levofloxacin HCl (<b>c</b>). The chemical structure of Eudragit<sup>®</sup> L100 and Eudragit<sup>®</sup> S100, where the ratio of x:y is 1:1 and 1:2, respectively.</p> "> Figure 2
<p>Physical appearance of Eudragit L (<b>A</b>) and Eudragit S (<b>B</b>)-based ISGs comprising different concentrations of polymers.</p> "> Figure 3
<p>Viscosity (<b>A</b>); relationship between shear stress and shear rates (<b>B</b>); injection force and energy from injectability test (<b>C</b>); contact angle on different surfaces (<b>D</b>); hardness (<b>E</b>) and adhesiveness (<b>F</b>) properties from the mechanical test of Eudragit L and S-based ISG formulations at 25 °C. The data represent triplicates. The asterisk symbol indicates significant difference (<span class="html-italic">p</span> < 0.05).</p> "> Figure 4
<p>Gel formation after injection into PBS (<b>A</b>) and agarose well (<b>B</b>) of Eudragit L-based ISG formulations and gel formation after injection into PBS (<b>C</b>) and agarose well (<b>D</b>) of Eudragit S-based ISG formulations.</p> "> Figure 5
<p>Physical appearance of levofloxacin HCl-loaded Eudragit L-based ISGs comprising different concentrations of polymer.</p> "> Figure 6
<p>Viscosity (<b>A</b>); relationship between shear stress and shear rates (<b>B</b>); injection force and energy from injectability test (<b>C</b>); contact angle on different surfaces (<b>D</b>); hardness (<b>E</b>) and adhesiveness (<b>F</b>) properties from the mechanical test of levofloxacin HCl-loaded Eudragit L-based ISG formulations at 25 °C. The data are represented in triplicate.</p> "> Figure 7
<p>Gel formation after injection into PBS (<b>A</b>) and agarose well (<b>B</b>) of levofloxacin HCl-loaded Eudragit L-based ISG.</p> "> Figure 8
<p>Interface interaction between noncolored agarose gel (the left side) against Eudragit L-based ISG formulation or mono propylene glycol containing SF or NR (the right side) at different time intervals under an inverted fluorescent microscope at a magnification of 400×.</p> "> Figure 9
<p>Interface interaction between sodium fluorescence-loaded agarose gel (the left side) against Eudragit L-based ISG formulation and monopropylene glycol without or containing NR (the right side) at different time intervals under the inverted fluorescent microscope at a magnification of 400×.</p> "> Figure 10
<p>Drug release from Levofloxacin HCl-loaded Eudragit L-based ISG formulations (n = 3) (mean ± S.D).</p> "> Figure 11
<p>SEM images of surface and cross-section of freeze-dried remnant of Eudragit L-based ISG formulations after release test for 7 days at magnification of 1000× and 5000×.</p> "> Figure 12
<p>SEM images of levofloxacin HCl powder (<b>A</b>); surface and cross-section of a freeze-dried remnant of levofloxacin HCl-loaded Eudragit L-based ISG formulations at a magnification of 1000× and 5000× (<b>B</b>).</p> "> Figure 13
<p>X-ray tomography image and %porosity using X-ray tomography of freeze-dried remnant after drug release test for 7 days of levofloxacin HCl-loaded Eudragit L-based ISG formulations.</p> "> Figure 14
<p>FTIR spectra of MP, LVM, LM20, LLM20, Eudragit L (raw material).</p> ">
Abstract
:1. Introduction
2. Results and Discussion
2.1. Drug-Free Eudragit-Based ISG
2.1.1. Physical Appearance, Viscosity and Rheology, Injectability, Contact Angle, and Mechanical Properties
2.1.2. Gel Formation of Eudragit-Based ISGs
2.2. Levofloxacin HCl-Loaded Eudragit-Based ISG
2.2.1. Physical Appearance, Viscosity and Rheology, Injectability, Contact Angle, and Mechanical Properties
2.2.2. Gel Formation of Levofloxacin HCl-Loaded Eudragit-Based ISG
2.2.3. Microscopic Interface Interaction
2.2.4. Drug Content and Release of Levofloxacin HCl-Loaded Eudragit-Based ISGs
2.2.5. Scanning Electron Microscopy (SEM)
2.2.6. In Vitro Degradation
2.2.7. X-ray Computed Microtomography (μCT)
2.2.8. Antimicrobial Activities
2.2.9. FOURIER Transform Infrared Spectroscopy (FTIR)
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Preparation of In Situ Forming Gel
4.3. Viscosity and Rheology Characterization
4.4. Contact Angle
4.5. Injectability
4.6. Mechanical Properties
4.7. Gel Formation Study
4.8. Interfacial Phenomena of Formulation-Aqueous Phase
4.9. Drug Content and In Vitro Drug Release Studies
4.10. Scanning Electron Microscopy (SEM)
4.11. In Vitro Degradation Test
- = initial weight of the sample
- = weight of remained sample at a specific time
4.12. X-ray Imaging and X-ray Tomographic Microscopy
4.13. Antimicrobial Activities
4.14. Fourier Transform Infrared (FTIR) Spectroscopy
4.15. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Formula | Zero Order | First Order | Higuchi’s | Korsmeyer–PEPPAS | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
r2 | msc | r2 | msc | r2 | msc | r2 | msc | k ± SD | n ± SD | Release Mechanism | |
LLM10 | 0.8048 | 1.3742 | 0.8683 | 1.9759 | 0.9058 | 2.5144 | 0.9770 | 3.5961 | 3.344 ± 1.837 | 0.444 ± 0.050 | Fickian diffusion |
LLM15 | 0.7118 | 0.9164 | 0.8872 | 2.0854 | 0.8945 | 2.0844 | 0.9503 | 2.6867 | 2.603 ± 0.666 | 0.367 ± 0.028 | Fickian diffusion |
LLM20 | 0.7941 | 1.2387 | 0.9090 | 2.3402 | 0.9188 | 2.3419 | 0.9320 | 2.3732 | 1.856 ± 0.819 | 0.444 ± 0.055 | Fickian diffusion |
Formula | Weight Loss (%) | ||||
---|---|---|---|---|---|
Day 1 | Day 3 | Day 5 | Day 7 | Day 14 | |
LLM10 | 85.39 ± 0.32 a | 91.96 ± 0.98 b | 94.53 ± 1.46 c | 94.96 ± 1.21 d | 100.00 ± 0.00 |
LLM15 | 80.22 ± 2.90 a | 86.95 ± 1.97 b | 87.91 ± 0.54 | 92.57 ± 1.92 | 100.00 ± 0.00 |
LLM20 | 72.81 ± 1.85 a | 82.02 ± 1.46 b | 85.95 ± 1.98 c | 90.21 ± 1.80 d | 100.00 ± 0.00 |
Formula | Clear Zone Diameter (mm.) Mean ± S.D. | |||||||
---|---|---|---|---|---|---|---|---|
S. aureus 6538 | S. aureus 4430 | S. aureus 6532 | S. aureus 25923 | E. coli 8739 | C. albicans 10231 | P. gingivalis ATCC 33277 | A. actinomycetemcomitans ATCC 29522 | |
MP | 12.7 ± 0.5 | 13.0 ± 0.8 | 12.3 ± 0.5 | 10.3 ± 0.5 | 14.7 ± 0.5 | 18.7 ± 1.2 | 17.0 ± 2.2 | 26.3 ± 0.5 |
LM10 | 11.7 ± 0.5 | 10.7 ± 0.5 | 11.7 ± 0.5 | 9.8 ± 0.2 | 12.0 ± 0.8 | 16.7 ± 0.5 | 12.0 ± 0.8 | 23.7 ± 0.5 |
LM15 | 10.5 ± 0.4 | 10.7 ± 0.5 | 10.7 ± 0.5 | - | 12.0 ± 1.4 | 16.0 ± 0.8 | 15.0 ± 1.4 | 23.3 ± 0.5 |
LM20 | 10.3 ± 1.2 | 9.7 ± 0.5 | 11.3 ± 1.2 | - | 12.7 ± 1.2 | 15.0 ± 0.8 | 13.3 ± 1.2 | 22.3 ± 0.5 |
LVM | 26.3 ± 0.9 a | 25.3 ± 0.9 b | 26.0 ± 0.8 c | 25.3 ± 0.5 d | 25.3 ± 0.9 e | 20.0 ± 1.6 f | 26.0 ± 0.8 g | >40 |
LLM10 | 26.7 ± 0.5 | 23.3 ± 0.5 | 23.3 ± 1.2 | 23.3 ± 0.5 | 23.3 ± 0.9 | 15.3 ± 2.1 | 25.3 ± 1.2 | >40 |
LLM15 | 25.3 ± 0.5 | 22.7 ± 0.5 b | 21.7 ± 0.5 c | 22.7 ± 1.2 d | 22.3 ± 0.5 e | 16.0 ± 0.8 f | 23.3 ± 1.2 | >40 |
LLM20 | 24.3 ± 0.5 a | 21.3 ± 0.9 b | 20.3 ± 0.5 c | 20.7 ± 0.5 d | 22.0 ± 0.8 e | 14.7 ± 0.9 f | 21.3 ± 0.5 g | >40 |
A | |||
Formula | Amount (% w/w) | ||
Eudragit L | MP | ||
LM5 | 5 | 95 | |
LM10 | 10 | 90 | |
LM15 | 15 | 85 | |
LM20 | 20 | 80 | |
LM25 | 25 | 75 | |
B | |||
Formula | Amount (% w/w) | ||
Eudragit S | MP | ||
SM5 | 5 | 95 | |
SM10 | 10 | 90 | |
SM15 | 15 | 85 | |
SM20 | 20 | 80 | |
SM25 | 25 | 75 | |
C | |||
Formula | Amount (% w/w) | ||
Levofloxacin HCl | Eudragit L | MP | |
LLM10 | 0.5 | 10 | 89.5 |
LLM15 | 0.5 | 15 | 84.5 |
LLM20 | 0.5 | 20 | 79.5 |
LVM | 0.5 | - | 95.5 |
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Senarat, S.; Tuntarawongsa, S.; Lertsuphotvanit, N.; Rojviriya, C.; Phaechamud, T.; Chantadee, T. Levofloxacin HCl-Loaded Eudragit L-Based Solvent Exchange-Induced In Situ Forming Gel Using Monopropylene Glycol as a Solvent for Periodontitis Treatment. Gels 2023, 9, 583. https://doi.org/10.3390/gels9070583
Senarat S, Tuntarawongsa S, Lertsuphotvanit N, Rojviriya C, Phaechamud T, Chantadee T. Levofloxacin HCl-Loaded Eudragit L-Based Solvent Exchange-Induced In Situ Forming Gel Using Monopropylene Glycol as a Solvent for Periodontitis Treatment. Gels. 2023; 9(7):583. https://doi.org/10.3390/gels9070583
Chicago/Turabian StyleSenarat, Setthapong, Sarun Tuntarawongsa, Nutdanai Lertsuphotvanit, Catleya Rojviriya, Thawatchai Phaechamud, and Takron Chantadee. 2023. "Levofloxacin HCl-Loaded Eudragit L-Based Solvent Exchange-Induced In Situ Forming Gel Using Monopropylene Glycol as a Solvent for Periodontitis Treatment" Gels 9, no. 7: 583. https://doi.org/10.3390/gels9070583
APA StyleSenarat, S., Tuntarawongsa, S., Lertsuphotvanit, N., Rojviriya, C., Phaechamud, T., & Chantadee, T. (2023). Levofloxacin HCl-Loaded Eudragit L-Based Solvent Exchange-Induced In Situ Forming Gel Using Monopropylene Glycol as a Solvent for Periodontitis Treatment. Gels, 9(7), 583. https://doi.org/10.3390/gels9070583