Chitosan and Anionic Solubility Enhancer Sulfobutylether-β-Cyclodextrin-Based Nanoparticles as Dexamethasone Ophthalmic Delivery System for Anti-Inflammatory Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Phase Solubility Studies and Determination of Inclusion Complex Constant
2.3. Job’s Plot
2.4. 1H-NMR Analysis
2.5. CS/SBE-β-CD NPs Preparation
2.6. DEX-Loaded NPs Preparation
2.7. DEX Quantification Using HPLC Method
2.8. NPs Characterization
2.8.1. Particle Size, PDI, and ζ-Potential
2.8.2. Differential Scanning Calorimetry
2.8.3. Fourier-Transform Infrared Spectroscopy (FT-IR)
2.8.4. Encapsulation Efficiency of DEX in NPs
2.8.5. Transmission Electron Microscopy (TEM)
2.9. Preparation of Bovine Eye Cornea
2.10. Ex Vivo Mucoadhesive Studies
2.11. In Vitro and Ex Vivo Permeation Studies
2.12. Bi-Directional Transport Studies on MDCKII-MDR1
2.13. Ocular Irritation Test
3. Results and Discussion
3.1. Characterization of DEX/SBE-β-CD Inclusion Complex
3.2. Nanoparticles Preparation and Characterization
3.3. Characterization of DEX-Loaded NPs
3.4. Ex Vivo Mucoadhesive Studies
3.5. In Vitro and Ex Vivo Permeation Studies
3.6. Bi-Directional Transport Studies on MDCKII-MDR1
3.7. Ocular Irritation Test
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Samples | 1% w/v SBE-β-CD Solution (mL) | 0.5% w/v CS Solution (mL) |
---|---|---|
Low Mw CS NPs | 1 | 1.4 |
Low Mw CS NPs | 2 | 5 |
Medium Mw CS NPs | 1 | 1.4 |
Medium Mw CS NPs | 2 | 5 |
High Mw CS NPs | 1 | 1.4 |
High Mw CS NPs | 2 | 5 |
Oligomer CS NPs | 1 | 1.4 |
Oligomer CS NPs | 2 | 5 |
Kinetic Model | Equations | |
---|---|---|
Zero Order | Dt =amount of drug dissolved in time t; D0 = initial amount of drug in solution; K0 = zero-order release constant; | |
First Order | C0 = initial drug concentration; K = first-order rate constant, t = time; | |
Higuchi | KH = Higuchi dissolution constant, t = time; | |
Hixson–Crowell | fi = fraction of drug dissolved in time t; Kβ = release constant; | |
Korsmeyer–Peppas | Mt/M∞ = fraction of drug released at time t; K = release rate constant, ɳ = release exponent. |
Formulation | Diameter (nm) | PDI | ζ-Potential (mV) | EE (%) |
---|---|---|---|---|
Low MW CS NPs | 210.3 ± 5.2 | 0.161 ± 0.047 | +29.4 ± 0.7 | / |
Medium MW CS NPs | 342.7 ± 9.3 | 0.327 ± 0.121 | +17.1 ± 0.5 | / |
High MW CS NPs | 391.1 ± 12.3 | 0.359 ± 0.174 | +19.6 ± 0.8 | / |
Oligomer CS NPs | / | / | / | / |
DEX-loaded Low MW CS NPs | 212.9 ± 5.3 | 0.155 ± 0.048 | +31.7 ± 0.4 | 87.1 |
Kinetic Model | R2 | n | R2 | n |
---|---|---|---|---|
0–60 min | 60–360 min | |||
Zero Order | 0.9847 | 0.9967 | ||
First Order | 0.9963 | 0.9653 | ||
Higuchi | 0.9377 | 0.9703 | ||
Hixson–Crowell | 0.9938 | 0.9793 | ||
Korsmeyer–Peppas | 0.9988 | 1.373 | 0.9612 | 2.502 |
Formulation | Flux (J) µg h−1 cm−2 | Apparent Permeability Coefficient Papp × 10−6 (cm/s) | Transport Enhancement Ratio R = [Papp(s)/Papp(c)] |
---|---|---|---|
DEX-loaded NPs | 6.64 | 2.13 ± 0.08 | 2.04 |
Control | 3.22 | 1.04 ± 0.02 | / |
Formulation | Papp AP-BL × 10−7 (cm/s) | Papp BL-AP × 10−7 (cm/s) | ER (PappBL/PappAP) |
---|---|---|---|
DEX | 0.66 ± 0.05 | 1.87 ± 0.07 | 2.84 |
DEX-loaded NPs | 0.92 ± 0.03 | 0.85 ± 0.03 | 0.92 |
Diazepam | 146 ± 10 | 123 ± 9 | 0.84 |
FD4 | 10 ± 1 | 2.0 ± 0.2 | 0.2 |
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Racaniello, G.F.; Balenzano, G.; Arduino, I.; Iacobazzi, R.M.; Lopalco, A.; Lopedota, A.A.; Sigurdsson, H.H.; Denora, N. Chitosan and Anionic Solubility Enhancer Sulfobutylether-β-Cyclodextrin-Based Nanoparticles as Dexamethasone Ophthalmic Delivery System for Anti-Inflammatory Therapy. Pharmaceutics 2024, 16, 277. https://doi.org/10.3390/pharmaceutics16020277
Racaniello GF, Balenzano G, Arduino I, Iacobazzi RM, Lopalco A, Lopedota AA, Sigurdsson HH, Denora N. Chitosan and Anionic Solubility Enhancer Sulfobutylether-β-Cyclodextrin-Based Nanoparticles as Dexamethasone Ophthalmic Delivery System for Anti-Inflammatory Therapy. Pharmaceutics. 2024; 16(2):277. https://doi.org/10.3390/pharmaceutics16020277
Chicago/Turabian StyleRacaniello, Giuseppe Francesco, Gennaro Balenzano, Ilaria Arduino, Rosa Maria Iacobazzi, Antonio Lopalco, Angela Assunta Lopedota, Hakon Hrafn Sigurdsson, and Nunzio Denora. 2024. "Chitosan and Anionic Solubility Enhancer Sulfobutylether-β-Cyclodextrin-Based Nanoparticles as Dexamethasone Ophthalmic Delivery System for Anti-Inflammatory Therapy" Pharmaceutics 16, no. 2: 277. https://doi.org/10.3390/pharmaceutics16020277