Docetaxel-Loaded Chitosan Microspheres as a Lung Targeted Drug Delivery System: In Vitro and in Vivo Evaluation
Abstract
:1. Introduction
2. Results and Discussion
2.1. Preparation and Microsphere Characterization
2.2. In Vitro Drug Release Behavior
2.3. Pharmacokinetic Studies
2.4. Biodistribution Studies
3. Materials and Methods
3.1. Materials
3.2. Preparation of the Microspheres
3.3. Morphological Characterization and Particle Sizing
3.4. Encapsulation Efficiency
3.5. Characterization of Microspheres
3.6. In Vitro Drug Release Studies
3.7. Pharmacokinetics Evaluation
3.8. Biodistribution Studies
3.9. LC-MS/MS Analysis
3.10. Statistical Analysis
4. Conclusions
Conflicts of Interest
References
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Time (month) | 4 °C | 25 °C | ||
---|---|---|---|---|
Drug remaining (%) | Surface morphology | Drug remaining (%) | Surface morphology | |
Initial | 99.6 | spherical | 101.3 | spherical |
1 | 100.1 | spherical | 101.7 | spherical |
2 | 101.2 | spherical | 99.7 | spherical |
3 | 99.2 | spherical | 98.9 | spherical |
Parameter | Formulations | |
---|---|---|
Injection | Microspheres | |
t1/2α (h) | 0.22 ± 0.1 | 0.86 ± 0.3 * |
t1/2β (h) | 4.9 ± 1.3 | 7.9 ± 3.4 * |
Cmax (ng/mL) | 1425.6 ± 154.6 | 1239.5 ± 136.3 |
AUC0–t (ng·h/mL) | 2234.6 ± 234.1 | 2555.6 ± 309.2 |
AUC0–∞ (ng·h/mL) | 2635.8 ± 253.2 | 2875.3 ± 339.6 |
MRT (h) | 12.8 ± 4.6 | 21.6 ± 3.9 * |
CL (L/h) | 25.8 ± 6.5 | 16.7 ± 4.2 * |
Formulation | Heart | Liver | Spleen | Lung | Kidney | Uterus/ovaries | Plasma |
---|---|---|---|---|---|---|---|
DTX injection (ng·h/g) | 1332.8 | 2671.6 | 1979.4 | 1772.9 | 6754.8 | 3139.8 | 1494.4 |
DTX-loaded microspheres (ng·h/g) | 613.1 | 376.3 | 1699.4 | 7720.6 | 651.9 | 776.1 | 698.5 |
Ratio a | 0.46 | 0.14 * | 0.86 | 4.35 * | 0.10 * | 0.25 * | 0.47 |
Parameter | Value |
---|---|
Scan type | MRM (multiple reaction monitoring) |
Ion polarity | Positive |
Fragmentor voltage, V | 115 |
Nebulizer pressure, psi | 35 |
Drying gas temperature, °C | 340 |
Dry gas flow, L/min | 32 |
Dwell time per transition, ms | 220 |
Resolution | Unit |
Collision energy, eV | 30 |
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Wang, H.; Xu, Y.; Zhou, X. Docetaxel-Loaded Chitosan Microspheres as a Lung Targeted Drug Delivery System: In Vitro and in Vivo Evaluation. Int. J. Mol. Sci. 2014, 15, 3519-3532. https://doi.org/10.3390/ijms15033519
Wang H, Xu Y, Zhou X. Docetaxel-Loaded Chitosan Microspheres as a Lung Targeted Drug Delivery System: In Vitro and in Vivo Evaluation. International Journal of Molecular Sciences. 2014; 15(3):3519-3532. https://doi.org/10.3390/ijms15033519
Chicago/Turabian StyleWang, Hao, Yongdong Xu, and Xiao Zhou. 2014. "Docetaxel-Loaded Chitosan Microspheres as a Lung Targeted Drug Delivery System: In Vitro and in Vivo Evaluation" International Journal of Molecular Sciences 15, no. 3: 3519-3532. https://doi.org/10.3390/ijms15033519