Cydonia oblonga-Seed-Mucilage-Based pH-Sensitive Graft Copolymer for Controlled Drug Delivery—In Vitro and In Vivo Evaluation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Extraction of Cydonia oblonga Mucilage
2.3. Preparation of Cydonia oblonga-Mucilage-Based Hydrogels
2.4. Physicochemical Properties of Hydrogels
2.4.1. Swelling Studies
2.4.2. Drug Loading
2.4.3. Fourier-Transform Infrared (FTIR) Analysis
2.4.4. Scanning Electron Microscopy (SEM)
2.4.5. In Vitro Drug Release Measurement
2.4.6. Percentage Drug Release
2.4.7. Evaluation of Release Kinetics
2.4.8. In Vivo Evaluation
Study Design for In Vivo Evaluation
Standard Preparation
HPLC Analysis
In Vivo Pharmacokinetic Evaluation
3. Results and Discussion
3.1. Percentage Yield and Chemical Reaction Scheme
3.2. Swelling Studies
3.2.1. Hydrogel Swelling at Different pHs
3.2.2. Effect of Polymer Concentration on Swelling Behavior of CM-co-AA and CM-co-MAA Hydrogels
3.2.3. Effect of Monomer Concentration on Swelling Behavior of CM-co-AA Hydrogels
3.2.4. Effect of Monomer Concentration on Swelling Behavior of CM-co-MAA Hydrogels
3.2.5. Effect of Crosslinker Concentration on Swelling Behavior of CM-co-AA and CM-co-MAA Hydrogels
3.2.6. Drug Loading
3.2.7. FTIR Characterization of Hydrogels
3.2.8. Scanning Electron Microscopy (SEM) of CM-co-AA and CM-co-MAA
3.2.9. In Vitro Drug Release from CM-co-AA and CM-co-MAA Hydrogels
Effect of pH
3.2.10. In Vitro Drug Release from CM-co-AA and CM-co-MAA Hydrogels with Different Polymer Concentration
3.2.11. In Vitro Drug Release from CM-co-AA, and CM-co-MAA Hydrogels with Varying Crosslinker (MBA) Concentration
3.2.12. In Vitro Drug Release from CM-co-AA Hydrogels with Varying Concentration of Acrylic Acid (AA)
3.2.13. In Vitro Drug Release from CM-co-MAA Hydrogels with Varying Concentration of MAA
3.2.14. Drug Release Kinetics
3.2.15. In Vivo Pharmacokinetic Evaluation
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Formulation Code | Polymer Cydonia oblonga Mucilage (g) | Crosslinker MBA (% Mole Ratio of Monomer) | Initiator KPS (% Mole Ratio of Monomer) | Acrylic Acid (g) |
---|---|---|---|---|
M-1 | 1 | 0.02 | 0.02 | 12.5 |
M-2 | 1 | 0.02 | 0.02 | 17.5 |
C-1 | 1 | 0.03 | 0.02 | 15 |
C-2 | 1 | 0.04 | 0.02 | 15 |
P-1 | 0.5 | 0.02 | 0.02 | 15 |
P-2 | 1.5 | 0.02 | 0.02 | 15 |
Formulation Code | Polymer Cydonia oblonga Mucilage (g) | Crosslinker MBA (% Mole Ratio of Monomer) | Initiator KPS (% Mole Ratio of Monomer) | Methacrylic Acid(g) |
---|---|---|---|---|
M-3 | 1 | 0.02 | 0.02 | 30 |
M-4 | 1 | 0.02 | 0.02 | 35 |
C-3 | 1 | 0.03 | 0.02 | 35 |
C-4 | 1 | 0.04 | 0.02 | 35 |
P-3 | 0.5 | 0.02 | 0.02 | 35 |
P-4 | 1.5 | 0.02 | 0.02 | 35 |
Chromatography | LC-20AD Shimadzu |
Column | C 18.5 μ, (250 mm × 4.6 mm) |
Mobile phase | Acetonitrile:methanol:20 mM ammonium acetate buffer (25:55:20) |
Flow rate | One milliliter per minute |
Temperature | Ambient |
Wavelength for detection | 274 nm |
Dilution solvent | HPLC graded water |
Retention time | 5.53 min |
Formulation | Zero-Order Model | First-Order Model | Higuchi Model | Korsmeyer–Peppas Model | Hixson–Crowell Model | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
code | R2 | K0 | R2 | K1 | R2 | kH | R2 | kKP | n | R2 | kHC |
M1 | 0.801 | 3.196 | 0.94 | 0.051 | 0.994 | 13.321 | 0.997 | 12.463 | 0.525 | 0.908 | 0.015 |
M2 | 0.613 | 4.351 | 0.946 | 0.105 | 0.939 | 18.49 | 0.943 | 10.107 | 0.451 | 0.892 | 0.028 |
M5 | 0.846 | 3.092 | 0.963 | 0.049 | 0.984 | 12.812 | 0.991 | 10.616 | 0.571 | 0.936 | 0.014 |
M6 | 0.74 | 3.528 | 0.926 | 0.063 | 0.951 | 14.79 | 0.951 | 14.168 | 0.516 | 0.883 | 0.018 |
C1 | 0.79 | 3.394 | 0.949 | 0.258 | 0.992 | 14.171 | 0.993 | 13.38 | 0.522 | 0.913 | 0.016 |
C2 | 0.82 | 3.24 | 0.954 | 0.053 | 0.99 | 13.473 | 0.993 | 11.997 | 0.544 | 0.924 | 0.015 |
C5 | 0.844 | 3.214 | 0.966 | 0.052 | 0.984 | 13.321 | 0.99 | 11.077 | 0.569 | 0.939 | 0.015 |
C6 | 0.861 | 3.036 | 0.968 | 0.047 | 0.977 | 12.546 | 0.987 | 9.857 | 0.59 | 0.943 | 0.014 |
P1 | 0.604 | 0.333 | 0.943 | 0.104 | 0.937 | 18.427 | 0.942 | 21.177 | 0.447 | 0.887 | 0.028 |
P2 | 0.654 | 3.964 | 0.933 | 0.082 | 0.958 | 16.784 | 0.961 | 18.531 | 0.463 | 0.876 | 0.022 |
P5 | 0.771 | 3.517 | 0.948 | 0.062 | 0.97 | 14.709 | 0.971 | 13.743 | 0.526 | 0.909 | 0.017 |
P6 | 0.854 | 3.186 | 0.968 | 0.051 | 0.98 | 13.183 | 0.989 | 10.649 | 0.58 | 0.942 | 0.015 |
Parameter | Unit | Hydrogel Formulation | Marketed Product |
---|---|---|---|
Lambda_z | 1/h | 0.094999903 | 0.0089321 |
Tmax | h | 4 | 2 |
Cmax | ng/mL | 156.4879899 | 96 |
AUC 0-t | ng/mL × h | 1321.630847 | 574.456 |
MRT 0-inf_obs | h | 8.807584284 | 4.91 |
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Sarfraz, M.; Tulain, U.R.; Erum, A.; Malik, N.S.; Mahmood, A.; Sumaira; Aslam, S.; Sandhu, M.A.; Tayyab, M. Cydonia oblonga-Seed-Mucilage-Based pH-Sensitive Graft Copolymer for Controlled Drug Delivery—In Vitro and In Vivo Evaluation. Pharmaceutics 2023, 15, 2445. https://doi.org/10.3390/pharmaceutics15102445
Sarfraz M, Tulain UR, Erum A, Malik NS, Mahmood A, Sumaira, Aslam S, Sandhu MA, Tayyab M. Cydonia oblonga-Seed-Mucilage-Based pH-Sensitive Graft Copolymer for Controlled Drug Delivery—In Vitro and In Vivo Evaluation. Pharmaceutics. 2023; 15(10):2445. https://doi.org/10.3390/pharmaceutics15102445
Chicago/Turabian StyleSarfraz, Muhammad, Ume Ruqia Tulain, Alia Erum, Nadia Shamshad Malik, Arshad Mahmood, Sumaira, Sidra Aslam, Mansur Abdullah Sandhu, and Muhammad Tayyab. 2023. "Cydonia oblonga-Seed-Mucilage-Based pH-Sensitive Graft Copolymer for Controlled Drug Delivery—In Vitro and In Vivo Evaluation" Pharmaceutics 15, no. 10: 2445. https://doi.org/10.3390/pharmaceutics15102445
APA StyleSarfraz, M., Tulain, U. R., Erum, A., Malik, N. S., Mahmood, A., Sumaira, Aslam, S., Sandhu, M. A., & Tayyab, M. (2023). Cydonia oblonga-Seed-Mucilage-Based pH-Sensitive Graft Copolymer for Controlled Drug Delivery—In Vitro and In Vivo Evaluation. Pharmaceutics, 15(10), 2445. https://doi.org/10.3390/pharmaceutics15102445