Development of a Mucoadhesive Liquid Crystal System for the Administration of Rifampicin Applicable in Tuberculosis Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Liquid Crystal Development
2.3. Incorporation of Rifampicin in Liquid Crystal Systems
2.4. Physico-Chemical Characterization of Liquid Crystal Systems
2.4.1. Characterization of Liquid Crystals by Polarized Light Microscopy
2.4.2. Continuous Rheological Analysis
2.4.3. Oscillatory Rheological Analysis
2.4.4. Assessment of Mucoadhesive Forces
2.4.5. X-ray Scattering at Low Angle (SAXS)
2.4.6. Differential Exploratory Calorimetry Analyses
2.5. Cytotoxicity Tests (Agar Diffusion Method)
2.6. Bacterial Killing Kinetics of the RIF Carrying LCS, a Bacterial Inoculum of Mtb
2.7. In Vivo Assay
Mouse Model Infection with Mtb
3. Results
3.1. Liquid Crystal Development
3.2. Incorporation of Rifampicin in Liquid Crystal Systems
3.3. Physico-Chemical Characterization of Liquid Crystal Systems
3.3.1. Characterization of Liquid Crystals by Polarized Light Microscopy
3.3.2. Continuous Rheological Analysis
3.3.3. Oscillatory Rheological Analysis
3.3.4. Assessment of Mucoadhesive Forces
3.3.5. X-ray Scattering at Low Angle (SAXS)
3.3.6. Differential Exploratory Calorimetry Analyses (DSC)
3.4. Cytoxicity Tests (Agar Diffusion Method)
3.5. Bacterial Kinetics
3.6. In Vivo Assay
Mouse Model Infection with M. tuberculosis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Grade | Cytotoxicity | Halo Size |
---|---|---|
0 | Absence | Absence of discoloration around of sample |
1 | Light | Discoloration zone limited to the area under the sample |
2 | Mild | Discoloration zone around the sample up to 0.5 cm |
3 | Moderate | Discoloration zone from 0.5 to 1.0 cm around the sample |
4 | Severe | Discoloration zone greater than 1.0 cm |
System | Composition | Aspect | |||||
---|---|---|---|---|---|---|---|
PPD (%) | Oleilamine (%) | PPD: Oleilamine 1:1 (w:w) (%) | Water (%) | Procetyl® AWS (%) | |||
9D | 30 | _ | _ | 20 | 50 | STVI | L. crystal |
10D | 40 | _ | _ | 10 | 50 | STVI | L. crystal |
9E | _ | 30 | _ | 20 | 50 | STBV | L. crystal |
10E | _ | 40 | _ | 10 | 50 | STBV | Precursor liquid crystal system |
9F | _ | _ | 30 | 20 | 50 | SOVI | Precursor liquid crystal system |
10F | _ | _ | 40 | 10 | 50 | SOBV | L. crystal |
System | Composition | |||||
---|---|---|---|---|---|---|
PPD (%) | Oleilamine (%) | PPD: Oleilamine 1:1 (w:w) (%) | Water (%) | Procetyl® AWS (%) | Rifampicim (µg·mL−1) | |
9DR | 30 | _ | _ | 20 | 50 | 0.150 |
10DR | 40 | _ | _ | 10 | 50 | 0.150 |
9ER | _ | 30 | _ | 20 | 50 | 0.150 |
10ER | _ | 40 | _ | 10 | 50 | 0.150 |
9FR | _ | _ | 30 | 20 | 50 | 0.150 |
10FR | _ | _ | 40 | 10 | 50 | 0.150 |
System | n | k | |
---|---|---|---|
Liquid Crystal System | 9D | 1.95 | 0.059 |
10D | 0.958 | 1.832 | |
9E | 0.917 | 0.185 | |
10E | 0.901 | 0.077 | |
9F | 0.787 | 0.434 | |
10F | 0.177 | 3.337 | |
Liquid Crystal System with rifampicin | 9DR | 0.540 | 3.452 |
10DR | 0.382 | 20.824 | |
9ER | 0.758 | 0.354 | |
10ER | 0.925 | 0.069 | |
9FR | 0.829 | 0.337 | |
10FR | 0.697 | 0.264 | |
Liquid Crystal System + SNF | 9D | 0.145 | 703.144 |
10D | 0.509 | 83.275 | |
9E | 0.415 | 55.683 | |
10E | 0.745 | 26.151 | |
9F | 0.486 | 77.446 | |
10F | 0.470 | 129.193 | |
Liquid Crystal System with rifampicin + SNF | 9DR | 0.229 | 319.585 |
10DR | 0.533 | 59.849 | |
9ER | 0.445 | 58.022 | |
10ER | 0.491 | 86.391 | |
9FR | 0.119 | 547.658 | |
10FR | 0.245 | 292.803 |
System | R | S | n | |
---|---|---|---|---|
Initial System (IS) | 9D | 0.987 | 164.282 | 0.155 |
10D | 0.982 | 853.439 | 0.116 | |
9E | 0.624 | 14.854 | 0.022 | |
10E | 0 | 9.791 | 8 × 10−13 | |
9F | 0.470 | 117.978 | 0.025 | |
10F | 0 | 330.185 | 1.3 × 10−11 | |
IS + Rifampicin | 9DR | 0.954 | 176.103 | 0.155 |
10DR | 0.957 | 86.734 | 0.292 | |
9ER | 0.862 | 12.844 | 0.045 | |
10ER | 0 | 9.922 | 6 × 10−3 | |
9FR | 0.801 | 16.532 | 0.053 | |
10FR | 0.867 | 205.799 | 0.157 | |
Initial System (IS) + SNF | 9D | 0.669 | 5970.146 | 0.232 |
10D | 0.902 | 3050.039 | 0.170 | |
9E | 0.841 | 914.508 | 0.113 | |
10E | 0.819 | 910.679 | 0.134 | |
9F | 0.743 | 1575.645 | 0.107 | |
10F | 0.691 | 2003.491 | 0.059 | |
SI + Rifampicin + SNF | 9DR | 0.454 | 3468.944 | 0.242 |
10DR | 0.725 | 2468.397 | 0.181 | |
9ER | 0.949 | 58.022 | 0.445 | |
10ER | 0.517 | 1947.099 | 0.132 | |
9FR | 0.091 | 8295.673 | 0.062 | |
10FR | 0.662 | 2380.354 | 0.174 |
System | qmax1 | qmax2 | qmax3 | d2/d1 | d3/d1 | Structure | |
---|---|---|---|---|---|---|---|
Initial System (IS) | 9D | 13,502,052.0 | 27,209,302.3 | 40,779,753.8 | 2 | 3 | Hexagonal |
10D | 13,577,291.0 | 21,767,587.8 | 43,661,650.7 | 2 | 3 | Hexagonal | |
9E | 9,913,284.3 | 19,887,965.9 | - | 2 | Lamellar | ||
10E | 11,524,167.8 | - | - | Microemulsion | |||
9F | 9,610,123.12 | 19,288,645.7 | - | 2 | Lamellar | ||
10F | 10,897,172.8 | - | - | Microemulsion | |||
IS + Rifampicin | 9DR | 13,555,631.6 | 27,173,962.6 | 41,005,472.0 | 2 | 3 | Hexagonal |
10DR | 13,578,263.8 | 27,088,719.0 | 43,661,650.7 | 2 | 3 | Hexagonal | |
9ER | 10,257,637.9 | 20,251,938.0 | - | 2 | Lamellar | ||
10ER | 11,737,346.1 | - | - | Microemulsion | |||
9FR | 9,664,842.6 | 19,418,604.7 | - | 2 | Lamellar | ||
10FR | 10,997,492 | - | - | Microemulsion |
System | Halo (mm) | Cytotoxicity |
---|---|---|
9D | 8.7 | Moderate |
10D | 8.8 | Moderate |
9E | 12 | Moderate |
10E | 7.7 | Moderate |
9F | 6.7 | Moderate |
10F | 5.9 | Moderate |
9DR | 5 | Light |
10DR | 5.8 | Moderate |
9ER | 8.5 | Moderate |
10ER | 7.4 | Moderate |
9FR | 6.8 | Moderate |
10FR | 6.6 | Moderate |
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Santos, K.P.; Rodero, C.F.; Ribeiro, C.M.; Gremião, M.P.D.; Peccinini, R.G.; Pavan, F.R.; Pearce, C.; Gonzalez-Juarrero, M.; Chorilli, M. Development of a Mucoadhesive Liquid Crystal System for the Administration of Rifampicin Applicable in Tuberculosis Therapy. Life 2022, 12, 1138. https://doi.org/10.3390/life12081138
Santos KP, Rodero CF, Ribeiro CM, Gremião MPD, Peccinini RG, Pavan FR, Pearce C, Gonzalez-Juarrero M, Chorilli M. Development of a Mucoadhesive Liquid Crystal System for the Administration of Rifampicin Applicable in Tuberculosis Therapy. Life. 2022; 12(8):1138. https://doi.org/10.3390/life12081138
Chicago/Turabian StyleSantos, Kaio Pini, Camila Fernanda Rodero, Camila Maríngolo Ribeiro, Maria P. D. Gremião, Rosângela Gonçalves Peccinini, Fernando Rogerio Pavan, Camron Pearce, Mercedes Gonzalez-Juarrero, and Marlus Chorilli. 2022. "Development of a Mucoadhesive Liquid Crystal System for the Administration of Rifampicin Applicable in Tuberculosis Therapy" Life 12, no. 8: 1138. https://doi.org/10.3390/life12081138