Experimental Investigation into the Design, Optimization, Toxicity, and Anti-Viral Efficacy of Proliposomes Loaded with Ivermectin Against Infectious Bronchitis Virus Using an Embryonated Chicken Egg Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Experimental Design
2.2.2. Preparation of IVM-Loaded PLs Formulations
2.2.3. Characterization of IVM-Loaded PLs Formulations
Estimation of Product Yield (PY%)
Estimation of Entrapment Efficiency (EE%)
Estimation of Particle Size (PS) and Polydispersity Index (PDI)
Zeta Potential Measurement (ZP)
Cumulative Percentage of Drug Released After 6 h (Q6h)
Kinetic Study of Drug Release
2.2.4. Optimization Technique
2.2.5. Characterization of the Selected Formulations
Scanning Electron Microscopy (SEM)
Differential Scanning Calorimetry (DSC)
Fourier Transform Infrared Spectroscopy (FTIR)
Stability Studies
2.2.6. Investigation of the Anti-Viral Activity Against IBV
Ethical Statement
Virus
Toxicity Study
Assay of Anti-Viral Activity
RNA Extraction, Reverse Transcription, and qRT-PCR
3. Results and Discussion
3.1. Preliminary Studies for Preparation of IVM-Loaded PLs
3.2. Analysis of Factorial Design
3.2.1. The Effect of Independent Variables on Product Yield (PY%; Y1)
3.2.2. The Effect of Independent Variables on Entrapment Efficiency (EE%; Y2)
3.2.3. The Effect of Independent Variables on Particle Size (PS; Y3)
3.2.4. The Effect of Independent Variables on Polydispersity Index (PDI; Y4)
3.2.5. The Effect of Independent Variables on Zeta Potential (ZP; Y5)
3.2.6. The Effect of Independent Variables on Drug Released After 6 h (Q6h; Y6)
3.2.7. Kinetic Study of Drug Release
3.3. Optimization Technique
3.4. Characterization of the Selected IVM-Loaded PLs Formulations
3.4.1. Scanning Electron Microscopy (SEM)
3.4.2. DSC Analysis
3.4.3. FTIR
3.4.4. Stability Studies
3.5. Investigation of the Anti-Viral Activity Against IBV
3.5.1. Toxicity Study
3.5.2. Assay of Anti-Viral Activity
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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Independent Factors | Factors Symbol | Unit | Factors Type | Factors Levels | |
---|---|---|---|---|---|
Low (−1) | High (+1) | ||||
Carrier/lipid phase (w/w) | A | --- | Numeric | 6:1 | 9:1 |
Amount of SG | B | mg | Numeric | Zero | 100 |
phospholipid type | C | --- | Categoric | SPC | DPPC |
Dependent Responses | Response Symbol | Unit | (Goals) | ||
Product yield | Y1 | % | Maximize | ||
Entrapment efficiency | Y2 | % | Maximize | ||
Particle size | Y3 | nm | Minimize | ||
Polydispersity index | Y4 | --- | Minimize | ||
Zeta potential | Y5 | mV | Maximize (as absolute value) | ||
Cumulative percentage of drug release after 6 h | Y6 | % | Maximize |
Formulation Code | A | B | C | PY% (Y1) | EE% (Y2) | PS (nm) (Y3) | PDI (Y4) | ZP (mV) (Y5) | Q6h (Y6) |
---|---|---|---|---|---|---|---|---|---|
PL1 | 9:1 | Zero | SPC | 92.7 ± 2.83 | 71.8 ± 2.01 | 330.1 ± 55.65 | 0.603 ± 0.03 | −42.4 ± 4.80 | 80.95 ± 1.36 |
PL2 | 6:1 | Zero | SPC | 88.6 ± 2.19 | 83.4 ± 0.81 | 385.7 ± 49.18 | 0.585 ± 0.04 | −50.1 ± 1.80 | 86.59 ± 3.01 |
PL3 | 9:1 | Zero | DPPC | 91.7 ± 1.93 | 81.2 ± 2.17 | 1358.3 ± 95.84 | 0.447 ± 0.02 | −25.4 ± 1.35 | 84.23 ± 4.56 |
PL4 | 6:1 | Zero | DPPC | 90.2 ± 2.61 | 88.9 ± 0.94 | 1462.3 ± 28.86 | 0.327 ± 0.01 | −18.2 ± 0.60 | 82.49 ± 1.69 |
PL5 | 9:1 | 100 | SPC | 98.5 ± 1.74 | 81.7 ± 1.32 | 490.3 ± 21.75 | 0.396 ± 0.06 | −40.1 ± 1.04 | 84.59 ± 4.19 |
PL6 | 6:1 | 100 | SPC | 97.3 ± 0.77 | 88.7 ± 1.40 | 523.7 ± 25.86 | 0.205 ± 0.06 | −42.4 ± 1.10 | 88.79 ± 2.03 |
PL7 | 9:1 | 100 | DPPC | 98.8 ± 0.45 | 87.9 ± 0.75 | 1695.3 ± 46.76 | 0.528 ± 0.08 | −20.1 ± 1.40 | 86.31 ± 1.45 |
PL8 | 6:1 | 100 | DPPC | 97.1± 1.15 | 96.1 ± 0.51 | 1801.6 ± 45.61 | 0.517 ± 0.05 | −19.7 ± 0.73 | 87.02 ± 1.88 |
Suggested Model | Y1 (%) | Y2 (%) | Y3 (nm) | Y4 | Y5 (mV) | Y6 (%) |
---|---|---|---|---|---|---|
Linear | Linear | Linear | 2-FI | Linear | 2-FI | |
p-Value | p-Value | p-Value | p-Value | p-Value | p-Value | |
Model | 0.0011 * | 0.0006 * | <0.0001 * | 0.4922 | 0.0056 * | 0.3698 |
A | 0.0216 * | 0.0007 * | 0.2073 | 0.4408 | 0.8404 | 0.2647 |
B | 0.0003 * | 0.0013 * | 0.0081 * | 0.4638 | 0.2842 | 0.1928 |
C | 0.7780 | 0.0014 * | <0.0001 * | 0.9325 | 0.0012 * | 0.8599 |
AB | --- | --- | --- | 0.8579 | --- | 0.8383 |
AC | --- | --- | --- | 0.8282 | --- | 0.2188 |
BC | --- | --- | --- | 0.2022 | --- | 0.8756 |
Significant factors | A, B | A, B, C | B, C | ---- | C | ---- |
R2 Analysis | ||||||
R2 | 0.9762 | 0.9821 | 0.9929 | 0.9237 | 0.9451 | 0.9589 |
Adequate precision | 16.2385 | 25.5932 | 29.4301 | 4.2675 | 9.6516 | 6.0941 |
Adjusted R2 | 0.9584 | 0.9688 | 0.9875 | 0.4659 | 0.9039 | 0.7124 |
Predicted R2 | 0.9049 | 0.9286 | 0.9715 | −3.8833 | 0.7803 | −1.6297 |
Release Model | R2 | |||||||
---|---|---|---|---|---|---|---|---|
PL1 | PL2 | PL3 | PL4 | PL5 | PL6 | PL7 | PL8 | |
Zero order | 0.1912 | 0.2646 | 0.2565 | 0.1951 | 0.0545 | 0.0737 | 0.0860 | 0.0536 |
First order | 0.8923 | 0.9381 | 0.9070 | 0.9100 | 0.9019 | 0.9403 | 0.9303 | 0.9257 |
Higuchi | 0.8727 | 0.9009 | 0.9012 | 0.8547 | 0.8131 | 0.8174 | 0.8122 | 0.8021 |
Korsmeyer–Peppas | 0.9612 | 0.9722 | 0.9762 | 0.9363 | 0.9387 | 0.9365 | 0.9236 | 0.9246 |
Hixson–Crowell | 0.7961 | 0.8662 | 0.8153 | 0.8312 | 0.8286 | 0.8886 | 0.8784 | 0.8710 |
Best fit model | Korsmeyer–Peppas | Korsmeyer–Peppas | Korsmeyer–Peppas | Korsmeyer–Peppas | Korsmeyer–Peppas | First order | First order | First order |
n-value of Korsmeyer–Peppas | 0.312 | 0.328 | 0.324 | 0.318 | 0.283 | 0.287 | 0.293 | 0.284 |
Y1 (%) | Y2 (%) | Y3 (nm) | Y4 | Y5 (mV) | Y6 (%) | |
---|---|---|---|---|---|---|
Predicted values | 96.775 | 89.35 | 591.675 | 0.240 | −42.325 | 89.276 |
Observed values | 97.3 | 88.7 | 523.7 | 0.205 | −42.4 | 88.79 |
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Alyami, M.H.; Alyami, H.S.; Abdo, A.M.; A. Sabry, S.; Mansour, S.M.G.; El-Nahas, H.M.; Ayoub, M.M. Experimental Investigation into the Design, Optimization, Toxicity, and Anti-Viral Efficacy of Proliposomes Loaded with Ivermectin Against Infectious Bronchitis Virus Using an Embryonated Chicken Egg Model. Pharmaceutics 2025, 17, 165. https://doi.org/10.3390/pharmaceutics17020165
Alyami MH, Alyami HS, Abdo AM, A. Sabry S, Mansour SMG, El-Nahas HM, Ayoub MM. Experimental Investigation into the Design, Optimization, Toxicity, and Anti-Viral Efficacy of Proliposomes Loaded with Ivermectin Against Infectious Bronchitis Virus Using an Embryonated Chicken Egg Model. Pharmaceutics. 2025; 17(2):165. https://doi.org/10.3390/pharmaceutics17020165
Chicago/Turabian StyleAlyami, Mohammad H., Hamad S. Alyami, Asmaa M. Abdo, Shereen A. Sabry, Shimaa M. G. Mansour, Hanan M. El-Nahas, and Margrit M. Ayoub. 2025. "Experimental Investigation into the Design, Optimization, Toxicity, and Anti-Viral Efficacy of Proliposomes Loaded with Ivermectin Against Infectious Bronchitis Virus Using an Embryonated Chicken Egg Model" Pharmaceutics 17, no. 2: 165. https://doi.org/10.3390/pharmaceutics17020165
APA StyleAlyami, M. H., Alyami, H. S., Abdo, A. M., A. Sabry, S., Mansour, S. M. G., El-Nahas, H. M., & Ayoub, M. M. (2025). Experimental Investigation into the Design, Optimization, Toxicity, and Anti-Viral Efficacy of Proliposomes Loaded with Ivermectin Against Infectious Bronchitis Virus Using an Embryonated Chicken Egg Model. Pharmaceutics, 17(2), 165. https://doi.org/10.3390/pharmaceutics17020165