Eudragit-Coated Sporopollenin Exine Microcapsules (SEMC) of Phoenix dactylifera L. of 5-Fluorouracil for Colon-Specific Drug Delivery
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Pollen Collection
2.2.2. Extraction of Sporopollenin Exine Microcapsules (SEMC)
2.2.3. Encapsulation of 5-FU into SEMC
2.2.4. Formulation of Eudragit® RS-100 (E-RS) Coated SEMC
2.2.5. Morphological Characterization of SEMC and Size Analysis
2.2.6. Porosity Determination of SEMC
2.2.7. FTIR Spectra
2.2.8. Powder X-ray Diffraction
2.2.9. Differential Scanning Calorimetry
2.3. Chromatographic Analysis of 5-FU
2.4. Encapsulation Efficiency (%EE) and Drug Loading (%DL)
2.5. In Vitro Drug Release Study
2.6. Stability of 5-FU-Loaded Uncoated and ERS-Coated SEMC
2.7. In Vivo Study
2.7.1. Animals
2.7.2. Pharmacokinetics and Gastrointestinal Distribution Study
2.8. Statistical Analysis
3. Results and Discussion
3.1. Formulation of 5-FU-Loaded SEMC and Its Coating by ERS
3.2. Structural Morphology and Size Analysis of SEMC
3.3. Porosity and Surface Volume Measurement
3.4. Fourier Transform Infrared (FTIR) Spectroscopy
3.5. Powdered X-ray Diffraction (PXRD)
3.6. Differential Scanning Calorimetry
3.7. Effect of 5-FU Concentration on Encapsulation and Its Loading into SEMC
3.8. In Vitro Release of 5-FU
3.9. Stability of 5-FU Loaded SEMC (Uncoated and ERS-Coated)
3.10. In Vivo Pharmacokinetics
3.11. Tissue Distribution of 5-FU in Stomach and Small Intestine
3.12. Tissue Distribution of 5 FU in Colon Tissues
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Formulations (Ratio of 5-FU/SEMC) | Amount (mg) | %EE (Mean ± SD) | %DL (Mean ± SD) | Size (µ) (Mean ± SD) | |
---|---|---|---|---|---|
5-FU | SEMC | ||||
F1 (1:4) | 50 | 200 | 47.66 ± 2.34 | 9.53 ± 0.46 | 12.42 ± 2.94 |
F2 (1:2) | 100 | 200 | 59.81 ± 4.19 | 19.94 ± 1.41 | 13.68 ± 3.91 |
F3 (3:4) | 150 | 200 | 58.86 ± 4.04 | 25.23 ± 1.73 | 17.02 ± 2.94 |
F2-ERS coated (with 5 mL of 5% ERS) | 100 | 200 | 56.23 ± 5.48 | 10.22 ± 0.99 | 15.47 ± 3.68 |
Stipulated Time Points | F2 Uncoated (Mean ± SD) | F2-ERS (Mean ± SD) | ||||
---|---|---|---|---|---|---|
Size (µ) | %EE | %DL | Size (µ) | %EE | %DL | |
Initially | 13.68 ± 3.91 | 59.81 ± 4.19 | 19.94 ± 1.39 | 15.47 ± 3.68 | 56.23 ± 5.48 | 10.22 ± 0.99 |
At 15th day | 13.86 ± 3.85 | 58.04 ± 3.48 | 19.34 ± 1.16 | 15.72 ± 3.75 | 55.03 ± 5.04 | 10.01 ± 0.92 |
At 30th day | 13.98 ± 3.81 | 56.95 ± 3.05 | 18.98 ± 1.02 | 15.87 ± 3.78 | 54.61 ± 5.24 | 9.93 ± 0.95 |
Pharmacokinetic Parameters | Plasma | Colon | Gastric | ||||||
---|---|---|---|---|---|---|---|---|---|
F2-ERS $ | F2 (Uncoated) $ | Change in % Control | F2-ERS $ | F2 (Uncoated) $ | Change in % Control | F2-ERS $ | F2 (Uncoated) $ | Change in % Control | |
Mean ± SD, n = 3 | Mean ± SD, n = 3 | Mean ± SD, n = 3 | Mean ± SD, n = 3 | Mean ± SD, n = 3 | Mean ± SD, n = 3 | ||||
Ke (1/h) | 0.09 ± 0.002 | 0.17 ± 0.0009 | 47.06 | 0.30 ± 0.0001 | 0.10 ± 0.000 | −200.00 | 0.06 ± 0.000 | 0.28 ± 0.028 | 785.71 |
t1/2 (h) | 7.38 ± 0.1875 | 4.03 ± 0.02 | −83.13 | 2.31 ± 0.0001 | 6.79 ± 0.0001 | 65.98 | 11.04 ± 0.0001 | 2.43 ± 0.23 | −354.32 |
Tmax (h) | 16.0 ± 0.0 | 1.0 ± 0.0 | −1500.00 | 12.0 ± 0.0 | 12.0 ± 0.0 | 0.00 | 3.0 ± 0.0 | 1.0 ± 0.0 | −200.00 |
Cmax (μg/mL) | 19.48 ± 0.61 | 102.82 ± 3.84 | 80.45 | 1271.53 ± 47.09 | 4.71 ± 0.06 | −26,896.39 | 23.55 ± 0.41 | 406.23 ± 15.04 | 94.20 |
AUC0-t (μg/mL·h) | 252.60 ± 6.24 | 264.09 ± 9.84 | 4.35 | 16,209.05 ± 600.34 | 64.86 ± 0.91 | −24,890.83 | 116.05 ± 2.01 | 1649.27 ± 71.14 | 92.96 |
AUC0-inf (μg/mL·h) | 350.54 ± 12.14 | 267.19 ± 9.83 | −31.20 | 16,509.59 ± 611.46 | 79.16 ± 1.11 | −20,755.98 | 129.98 ± 2.25 | 1651.17 ± 71.48 | 92.13 |
AUMC0-inf (μg/mL·h2) | 7212.19 ± 337.23 | 1387.17 ± 47.14 | −419.92 | 223,020.8 ± 8260.02 | 1218.264 ± 17.16 | −18,206.44 | 1322.44 ± 22.92 | 6941.41 ± 445.61 | 80.95 |
MRT0-inf (h) | 20.56 ± 0.29 | 5.19 ± 0.02 | −296.15 | 13.51 ± 0.001 | 15.38 ± 0.001 | 12.16 | 10.17 ± 0.001 | 4.20 ± 0.09 | −142.14 |
Vz/F {(mg)/(μg/mL)} | 0.24 ± 0.005 | 0.17 ± 0.007 | −41.18 | 0.002 ± 0.001 | 0.99 ± 0.01 | 99.80 | 0.99 ± 0.02 | 0.017 ± 0.001 | −5723.53 |
Cl/F {(mg)/(μg/mL)/h} | 0.023 ± 0.001 | 0.031 ± 0.001 | 25.81 | 0.001 ± 0.0001 | 0.102 ± 0.001 | 99.02 | 0.062 ± 0.001 | 0.005 ± 0.001 | −1140.00 |
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Raish, M.; Kalam, M.A.; Ahmad, A.; Shahid, M.; Ansari, M.A.; Ahad, A.; Ali, R.; Bin Jardan, Y.A.; Alshamsan, A.; Alkholief, M.; et al. Eudragit-Coated Sporopollenin Exine Microcapsules (SEMC) of Phoenix dactylifera L. of 5-Fluorouracil for Colon-Specific Drug Delivery. Pharmaceutics 2021, 13, 1921. https://doi.org/10.3390/pharmaceutics13111921
Raish M, Kalam MA, Ahmad A, Shahid M, Ansari MA, Ahad A, Ali R, Bin Jardan YA, Alshamsan A, Alkholief M, et al. Eudragit-Coated Sporopollenin Exine Microcapsules (SEMC) of Phoenix dactylifera L. of 5-Fluorouracil for Colon-Specific Drug Delivery. Pharmaceutics. 2021; 13(11):1921. https://doi.org/10.3390/pharmaceutics13111921
Chicago/Turabian StyleRaish, Mohammad, Mohd Abul Kalam, Ajaz Ahmad, Mudassar Shahid, Mushtaq Ahmad Ansari, Abdul Ahad, Raisuddin Ali, Yousef A. Bin Jardan, Aws Alshamsan, Musaed Alkholief, and et al. 2021. "Eudragit-Coated Sporopollenin Exine Microcapsules (SEMC) of Phoenix dactylifera L. of 5-Fluorouracil for Colon-Specific Drug Delivery" Pharmaceutics 13, no. 11: 1921. https://doi.org/10.3390/pharmaceutics13111921