Characterization, in Vitro and in Vivo Evaluation of Naringenin-Hydroxypropyl-β-Cyclodextrin Inclusion for Pulmonary Delivery
Abstract
:1. Introduction
2. Results and Discussion
2.1. Phase Solubility Study
2.2. Powder X-ray Diffraction (XRD)
2.3. Differential Scanning Calorimetry (DSC)
2.4. Proton Nuclear Magnetic Resonance (1HNMR) and Two Dimensional Rotating frame Overhauser Effect Spectroscopy (2D-ROESY) Studies
2.5. Permeation Study
2.6. Pharmacokinetic Studies
3. Materials and Methods
3.1. Materials
3.2. Phase Solubility Study
3.3. Preparation of Naringenin-HPβCD Inclusion
3.4. XRD
3.5. DSC
3.6. HNMR and 2D ROESY
3.7. Permeation Study of Naringenin- HPβCD Inclusion
3.7.1. Cell Culture
3.7.2. TEER Values Measurement
3.7.3. Permeation Study
3.7.4. HPLC Assay
3.8. Pharmacokinetic Study
3.8.1. Animals
3.8.2. Administration Protocol
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Compound | Proton | Chemical Shift δ (ppm) | Δδ (ppm) | |
---|---|---|---|---|
δ (Free) | δ (Inclusion) | |||
Naringenin | 2 | 5.438 | 5.427 | −0.011 |
6 or 8 | 5.878 | 5.857 | −0.021 | |
3′ or 5′ | 6.789 | 6.785 | −0.004 | |
2′ or 6′ | 7.312 | 7.308 | −0.004 | |
HPβCD | H-3 | 3.736 | 3.755 | 0.019 |
H-5 | 3.468 | 3.470 | 0.002 |
Day | 4 | 8 | 10 | 12 | 14 |
---|---|---|---|---|---|
TEER (Ω) | 212 ± 25 | 462 ± 33 | 510 ± 70 | 576 ± 30 | 581 ± 31 |
Form | Permeated Amount (μg/well) | Flux (μg/s × 10−4) |
---|---|---|
Naringenin solution | 3.61 ± 0.11 | 5.03 ± 0.16 |
Naringenin inclusion | 2.53 ± 0.06 | 3.52 ± 0.09 |
Naringenin suspension | 1.78 ± 0.30 | 2.47 ± 0.40 |
Parameter | IV | IT |
---|---|---|
AUC0-t (μg/L∗h) | 268.20 ± 85.62 | 233.60 ± 37.47 |
AUC(0-∞) (μg/L∗h) | 273.00 ± 84.46 | 291.15 ± 77.18 |
Tmax (h) | 0.083 | 0.181 ± 0.034 |
Cmax (μg/L) | 713.12 ± 258.564 | 217.86 ± 66.35 |
t1/2 (h) | 2.25 ± 0.90 | 4.15 ± 2.13 |
Clearance (L/h/kg) | 1.59 ± 0.51 | 1.46 ± 0.38 |
Bioavailability (%) | 87 1 |
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Guan, M.; Shi, R.; Zheng, Y.; Zeng, X.; Fan, W.; Wang, Y.; Su, W. Characterization, in Vitro and in Vivo Evaluation of Naringenin-Hydroxypropyl-β-Cyclodextrin Inclusion for Pulmonary Delivery. Molecules 2020, 25, 554. https://doi.org/10.3390/molecules25030554
Guan M, Shi R, Zheng Y, Zeng X, Fan W, Wang Y, Su W. Characterization, in Vitro and in Vivo Evaluation of Naringenin-Hydroxypropyl-β-Cyclodextrin Inclusion for Pulmonary Delivery. Molecules. 2020; 25(3):554. https://doi.org/10.3390/molecules25030554
Chicago/Turabian StyleGuan, Minyi, Rui Shi, Yuying Zheng, Xuan Zeng, Weiyang Fan, Yonggang Wang, and Weiwei Su. 2020. "Characterization, in Vitro and in Vivo Evaluation of Naringenin-Hydroxypropyl-β-Cyclodextrin Inclusion for Pulmonary Delivery" Molecules 25, no. 3: 554. https://doi.org/10.3390/molecules25030554