Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration
Abstract
:1. Introduction
2. Results and Discussion
2.1. Results
2.1.1. Cell Growth Inhibition Assay
2.1.2. Determination of Bioadhesive Force
2.1.3. In Vitro Drug Release Study
2.1.4. In Vitro Drug Permeation and Accumulation Tests in Rectal Mucosa
2.1.5. FTIR Analysis
2.1.6. In Vivo Localization of Suppository in the SD Rats
2.1.7. In Vivo Pharmacokinetic Study
2.1.8. Antitumor Efficacy
2.2. Discussion
3. Experimental Section
3.1. Materials
3.2. Preparation of Epi in Plu/PAA Formulation
3.2.1. Preparation of Plu/PAA Mixture
3.2.2. Preparation of Epi in Plu/PAA Liquid Suppository
3.2.3. Preparation of Epi in Plu/PAA Solid Suppository
3.3. Cell Culture
3.4. Cell Growth Inhibition Assay
3.5. Determination of Bioadhesive Force
3.6. In Vitro Drug Release Study
3.7. Epi Concentration Analyzed Using HPLC
3.8. In Vitro Drug Penetration Test
3.9. In Vitro Drug Accumulation Study
3.10. FT-IR Analysis
3.11. Identification of Suppository Localization in Vivo
3.12. In Vivo Pharmacokinetic Study
3.13. Establishment of in Vivo Model of Mouse Tumor Xenografts
3.14. In Vivo Antitumor Efficacy
3.15. Statistical Analysis
4. Conclusions
Supplementary Information
ijms-15-00342-s001.pdfAcknowledgments
Conflicts of Interest
References
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Hydrogel formulations | Composition (wt %) | |
---|---|---|
Formulation 1 | Plu 14%/PAA 0.75%/Epi 50 μg/mL | Liquid suppository |
Formulation 2 | Plu 14%/PAA 0.375%/Epi 50 μg/mL | |
Formulation 3 | Plu 14%/PAA 0.1875%/Epi 50 μg/mL | |
Formulation 4 | Cocoa butter 0.5 g/Plu 14%/PAA 0.75%/Epi 50 μg/mL | Solid suppository |
Formulation 5 | Cocoa butter 0.5 g/Plu 14%/PAA 0.375%/Epi 50 μg/mL | |
Formulation 6 | Cocoa butter 0.5 g/Plu 14%/PAA 0.1875%/Epi 50 μg/mL |
Suppository formulations | Fmax (g) |
---|---|
Formulation 1 | 6.70 ± 0.23 |
Formulation 2 | 5.39 ± 0.27 |
Formulation 3 | 3.78 ± 0.13 |
Formulation 4 | 6.99 ± 0.25 |
Formulation 5 | 5.64 ± 0.21 |
Formulation 6 | 4.05 ± 0.29 |
Cocoa butter | 5.94 ± 0.57 |
Formulations | Cmax (μg/mL) | Tmax (h) | AUC0→∞ (h × μg/mL) | %Fr |
---|---|---|---|---|
Intravenous Epi | 100.00 ± 0.00 †,‡,§,& | 0 | 34.38 ± 0.85 †,‡,§,& | 100.00 ± 2.47 †,‡,§,& |
Rectal Epi | 2.81 ± 1.38 * | 2 | 17.26 ± 1.95 *,‡,§,& | 50.20 ± 5.67 *,‡,§,& |
Oral Epi in Plu/PAA | 3.01 ± 1.08 * | 3 | 22.85 ± 2.04 *,† | 66.46 ± 5.93 *,† |
Epi in liquid suppository | 3.36 ± 2.17 * | 3 | 23.04 ± 2.37 *,† | 67.02 ± 6.89 *,† |
Epi in solid suppository | 3.16 ± 1.18 * | 3 | 22.14 ± 2.07 *,† | 64.40 ± 6.02 *,† |
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Lo, Y.-L.; Lin, Y.; Lin, H.-R. Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration. Int. J. Mol. Sci. 2014, 15, 342-360. https://doi.org/10.3390/ijms15010342
Lo Y-L, Lin Y, Lin H-R. Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration. International Journal of Molecular Sciences. 2014; 15(1):342-360. https://doi.org/10.3390/ijms15010342
Chicago/Turabian StyleLo, Yu-Li, Yijun Lin, and Hong-Ru Lin. 2014. "Evaluation of Epirubicin in Thermogelling and Bioadhesive Liquid and Solid Suppository Formulations for Rectal Administration" International Journal of Molecular Sciences 15, no. 1: 342-360. https://doi.org/10.3390/ijms15010342