Chitosan Nanoparticles for Meloxicam Ocular Delivery: Development, In Vitro Characterization, and In Vivo Evaluation in a Rabbit Eye Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Solubility Study of MLX
2.3. Preparation of MLX-CS-NPs
2.4. In Vitro Characterization of the Prepared MLX-CS-NPs
2.4.1. Entrapment Efficiency (EE%)
2.4.2. Evaluation of the Average Particle Size, Zeta Potential, and Morphology
2.4.3. pH Determination
2.4.4. Viscosity Measurements
2.4.5. Fourier Transform Infrared Spectroscopy (FTIR) Analysis
2.4.6. In Vitro Release Studies and Kinetic Analysis of the Release Data
2.4.7. Ex Vivo Ocular Permeation Study
Permeation Data Analysis
2.5. Preparation of MLX-CS-NPs Eye Drop Dispersion for the In Vivo Studies
2.6. In Vivo Studies
2.6.1. Eye Irritancy Evaluation
- Group I:
- Blank CS/PEG 400 eye drop solution (drug-free).
- Group II:
- MLX-eye drop solution.
- Group III:
- MLX-CS-NPs eye drop dispersion.
2.6.2. Anti-Inflammatory Activity Study
- Group I:
- Blank CS/PEG 400 eye drop solution (drug-free)
- Group II:
- MLX-eye drop solution.
- Group III:
- MLX-CS-NPs eye drop dispersion.
2.6.3. Histopathological Examination
2.7. Statistical Analyses
3. Results and Discussion
3.1. Solubility Study of MLX
3.2. Preparation and Characterization of MLX-CS-NPs
3.2.1. Morphology, Entrapment Efficiency, Average Particle Size, and Zeta Potential Measurements
3.2.2. Fourier Transform Infrared Spectroscopy (FTIR)
3.2.3. In Vitro Release and Kinetic Studies
3.2.4. Ex Vivo Corneal and Scleral Permeability
3.3. In Vivo Studies
3.3.1. Eye Irritancy Assessment
3.3.2. In Vivo Anti-Inflammatory Study
3.3.3. Pathohistological Examination
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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System Code | Polymers | |||||
---|---|---|---|---|---|---|
PG (% w/v) | HPβ-CD (% w/v) | PVP (% w/v) | HPβ-CD (10% w/v): PF-127 (5% w/v) | TPP (% w/v) | PEG 400 (%) | |
A1 | 10 | ------ | ------ | ------ | ------ | ------ |
A2 | 20 | ------ | ------ | ------ | ------ | ------ |
A3 | 100 | ------ | ------ | ------ | ------ | ------ |
A4 | ------ | 1 | ------ | ------ | ------ | ------ |
A5 | ------ | 2.5 | ------ | ------ | ------ | ------ |
A6 | ------ | 5 | ------ | ------ | ------ | ------ |
A7 | ------ | 10 | ------ | ------ | ------ | ------ |
A8 | ------ | ------ | ------ | 9:1 | ------ | ------ |
A9 | ------ | ------ | ------ | 8:2 | ------ | ------ |
A10 | ------ | ------ | ------ | 7:3 | ------ | ------ |
A11 | ------ | ------ | ------ | 6:4 | ------ | ------ |
A12 | ------ | ------ | ------ | 5:5 | ------ | ------ |
A13 | ------ | ------ | ------ | 4:6 | ------ | ------ |
A14 | ------ | ------ | ------ | 3:7 | ------ | ------ |
A15 | ------ | ------ | ------ | 2:8 | ------ | ------ |
A16 | ------ | ------ | ------ | 1:9 | ------ | ------ |
A17 | ------ | ------ | ------ | ------ | 0.1 | ------ |
A18 | ------ | ------ | ------ | ------ | 0.25 | ------ |
A19 | ------ | 1 | 1 | ------ | ------ | ------ |
A20 | ------ | 2 | 1 | ------ | ------ | ------ |
A21 | ------ | 3 | 1 | ------ | ------ | ------ |
A22 | ------ | 4 | 1 | ------ | ------ | ------ |
A23 | ------ | 5 | 1 | ------ | ------ | ------ |
A24 | ------ | 6 | 1 | ------ | ------ | ------ |
A25 | ------ | 7 | 1 | ------ | ------ | ------ |
A26 | ------ | 8 | 1 | ------ | ------ | ------ |
A27 | ------ | 9 | 1 | ------ | ------ | ------ |
A28 | ------ | 10 | 1 | ------ | ------ | ------ |
A29 | ------ | ------ | ------ | ------ | ------ | 100 |
Formulation Number | Chitosan (% w/v) | Acetic Acid (% v/v) | MLX (mg) | 0.25% w/v TPP (mL) | PEG 400 (mL) |
---|---|---|---|---|---|
F1 | 0.5 | 1 | 1 | 1 | - |
F2 | 0.5 | 1 | 1.5 | 1 | - |
F3 | 0.5 | 1 | 3.7 | - | 1 |
F4 | 0.25 | 0.5 | 1 | 1 | - |
F5 | 0.25 | 0.5 | 1.5 | 1 | - |
F6 | 0.25 | 0.5 | 3.7 | - | 1 |
Score | Discomfort | Cornea | Conjunctiva | Discharge | Lids |
---|---|---|---|---|---|
0 | No reaction | No changes | No changes | None | No edema |
1 | Blinking | Mild opacity |
| Mild, without wetted hair | Mild edema |
2 |
| Intense opacity |
| Intense, with wetted hair | Observed edema |
Assessment | Score |
---|---|
Normal surface epithelium with intact microvilli and tight junctions | 0 |
Some superficial cell sloughing and pitting with reduced microvilli | 1 |
Denuded superficial cells with intact underlying cells | 2 |
Partial loss of wing cells in the middle epithelial layer | 3 |
Loss of outermost epithelial cells exposing the basal epithelial cells | 4 |
Systems | Apparent MLX Solubility at 37 °C (mg/mL) | Comments |
---|---|---|
A1 (10% PG) | 0.027 | Increase MLX solubility with increasing PG concentration |
A2 (20% PG) | 0.05 | |
A3 (100% PG) | 0.28 | |
A4 (1% HP-β-CD) | 0.022 | Increase MLX solubility with increasing HP-β-CD concentration |
A5 (2.5% HP-β-CD) | 0.048 | |
A6 (5% HP-β-CD) | 0.095 | |
A7 (10% HP-β-CD) | 0.18 | |
A8 (10% HP-β-CD:5% PF-127) (9:1) | 0.15 | Decrease MLX solubility with decreasing the amount of HP-β-CD |
A9 (10% HP-β-CD:5% PF-127) (8:2) | 0.089 | |
A10 (10% HP-β-CD:5% PF-127) (7:3) | 0.082 | |
A11 (10% HP-β-CD:5% PF-127) (6:4) | 0.076 | |
A12 (10% HP-β-CD:5% PF-127) (5:5) | 0.072 | |
A13 (10% HP-β-CD:5% PF-127) (4:6) | 0.068 | |
A14 (10% HP-β-CD:5% PF-127) (3:7) | 0.062 | |
A15 (10% HP-β-CD:5% PF-127) (2:8) | 0.058 | |
A16 (10% HP-β-CD:5% PF-127) (1:9) | 0.055 | |
A17 (0.1%TPP) | 1.3 | Increase MLX solubility with increasing TPP concentration |
A18 (0.25% TPP) | 1.9 | |
A19 (1% HP-β-CD + 1% PVP) | 0.026 | Increase MLX solubility by increasing the percent of HP-β-CD in the presence of 1% PVP |
A20 (2% HP-β-CD + 1% PVP) | 0.041 | |
A21 (3% HP-β-CD + 1% PVP) | 0.052 | |
A22 (4% HP-β-CD + 1% PVP) | 0.072 | |
A23 (5% HP-β-CD + 1% PVP) | 0.098 | |
A24 (6% HP-β-CD + 1% PVP) | 0.11 | |
A25 (7% HP-β-CD + 1% PVP) | 0.14 | |
A26 (8% HP-β-CD + 1% PVP) | 0.16 | |
A27 (9% HP-β-CD + 1% PVP) | 0.19 | |
A28 (10% HP-β-CD + 1% PVP) | 0.23 | |
A29 (PEG 400) | 3.8 | Highest MLX solubility |
Formulation No. | Average Particle Size (nm) | PDI | Zeta Potential (mV) | EE (%) | pH |
---|---|---|---|---|---|
F1 | 335 ± 23 | 0.41± 0.0 | 49.2 ± 1.0 | 72 ± 4.5 | 5.6 ± 0.1 |
F2 | 597 ± 14 | 0.36 ± 0.1 | 44.4 ± 2.8 | 75 ± 2.0 | 6.2 ± 0.2 |
F3 | 195 ± 30 | 0.42 ± 0.0 | 28.2 ± 1.1 | 96 ± 1.5 | 5.6 ± 0.1 |
F4 | 266 ± 24 | 0.34 ± 0.1 | 57.0 ± 1.1 | 71 ± 2.0 | 5.5 ± 0.1 |
F5 | 493 ± 36 | 0.46 ± 0.0 | 55.9 ± 1.1 | 70 ± 2.5 | 6.3 ± 0.1 |
F6 | 242 ± 35 | 0.51 ± 0.0 | 17.3 ± 0.5 | 91 ± 2.0 | 5.5 ± 0.2 |
Formulations | Zero-Order | First-Order | Higuchi | Korsmeyer-Peppas |
---|---|---|---|---|
R2 | R2 | R2 | N | |
MLX-CS-NPs dispersion | 0.75 | 0.78 | 0.87 | 0.69 |
MLX solution in PEG 400 | 0.99 | 0.91 | 0.94 | 0.96 |
Formulation | Permeation Parameters | |||
---|---|---|---|---|
Cornea | Sclera | |||
J (µg·cm−2·h−1) | P (cm·h−1) | J (µg·cm−2·h−1) | P (cm·h−1) | |
MLX-CS-NPs dispersion | 29.9 | 0.0199 | 23.7 | 0.0158 |
MLX solution in PEG 400 | 95.1 | 0.0634 | 36.8 | 0.0246 |
Experiment Groups | The Average Score of Eye Inflammation | ||
---|---|---|---|
Before the Start of Treatment | After One Day of Treatment | After Three Days of Treatment | |
Group I: Blank CS/PEG 400 eye drop solution | 8 ± 0.3 | 6.3 ± 0.7 | 2.7 ± 0.5 |
Group II: MLX-eye drop solution | 10 ± 0.8 | 7.3 ± 0.8 | 5.0 ± 0.7 |
Group III: MLX-CS-NPs eye drop dispersion. | 10 ± 1.0 | 4.0 ± 0.5 | 0.3 ± 0.2 |
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Mohamed, H.B.; Attia Shafie, M.A.; Mekkawy, A.I. Chitosan Nanoparticles for Meloxicam Ocular Delivery: Development, In Vitro Characterization, and In Vivo Evaluation in a Rabbit Eye Model. Pharmaceutics 2022, 14, 893. https://doi.org/10.3390/pharmaceutics14050893
Mohamed HB, Attia Shafie MA, Mekkawy AI. Chitosan Nanoparticles for Meloxicam Ocular Delivery: Development, In Vitro Characterization, and In Vivo Evaluation in a Rabbit Eye Model. Pharmaceutics. 2022; 14(5):893. https://doi.org/10.3390/pharmaceutics14050893
Chicago/Turabian StyleMohamed, Hebatallah B., Mohamed Ali Attia Shafie, and Aml I. Mekkawy. 2022. "Chitosan Nanoparticles for Meloxicam Ocular Delivery: Development, In Vitro Characterization, and In Vivo Evaluation in a Rabbit Eye Model" Pharmaceutics 14, no. 5: 893. https://doi.org/10.3390/pharmaceutics14050893
APA StyleMohamed, H. B., Attia Shafie, M. A., & Mekkawy, A. I. (2022). Chitosan Nanoparticles for Meloxicam Ocular Delivery: Development, In Vitro Characterization, and In Vivo Evaluation in a Rabbit Eye Model. Pharmaceutics, 14(5), 893. https://doi.org/10.3390/pharmaceutics14050893