Celecoxib Loaded In-Situ Provesicular Powder and Its In-Vitro Cytotoxic Effect for Cancer Therapy: Fabrication, Characterization, Optimization and Pharmacokinetic Evaluation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Systematic Design of Experiments
2.2.2. Preparation of CLX-Loaded In-Situ Provesicular Powders
2.2.3. Formation of CLX-Loaded Nanovesicles
2.2.4. Characterization of the Prepared CLX-Loaded Nanovesicles Formulations
Vesicle Size (PS), Polydispersity Index (PDI) and Surface Charge (ZP) Determination
Determination of CLX Entrapment Efficiency (EE %) in the Prepared Nanovesicles
Optimization of Formulation Variables
2.2.5. Micromeritic Properties of the Optimized CLX-Loaded Provesicular Powder Formulation
2.2.6. Solid State Characterization of the Prepared Optimized Formulation
Thermal Analysis Using Differential Scanning Calorimetry (DSC)
Fourier Transform Infrared (FT-IR) Spectroscopy
Surface Characteristics of the Optimized CLX-Loaded Provesicular Powder Using Scanning Electron Microscopy Analysis
2.2.7. Morphology of the Optimized CLX-Loaded Nanovesicles Using Transmission Electron Microscopy
2.2.8. In-Vitro Release of CLX from the Optimized Formulation
2.2.9. In-Vitro Cytotoxicity Study of the CLX-IPP Optimized Formula Using MTT-Assay
Cell Lines and Cell Culture
Antiproliferative Activity (MTT-Assay)
2.2.10. Pharmacokinetic Study of CLX in Rabbits
The Design of the Pharmacokinetic Study
Drug Assay in Plasma
Pharmacokinetic Analysis
2.2.11. Statistical Analysis
3. Results and Discussion
3.1. Effect of Formulation Variables on the PS of the Prepared CLX Nanovesicles
3.2. Effect of Formulation Variables on ZP of the Prepared CLX Nanovesicles
3.3. Effect of Formulation Variables on EE % of the Prepared CLX Nanovesicles
3.4. Optimization of Formulation Variables
3.5. Micromeritic Properties of the Optimized CLX-Loaded Provesicular Powder Formulation
3.6. Solid State Characterization of the Prepared Optimized Formulation
3.6.1. Thermal Analysis Using Differential Scanning Calorimetry (DSC)
3.6.2. Fourier Transform Infrared (FT-IR) Spectroscopy
3.6.3. Surface Characteristics of the Optimized CLX-Loaded Provesicular Powder Using SEM
3.7. Morphology of the Optimized CLX-Loaded Nanovesicles Using TEM
3.8. In-Vitro Release of CLX from the Optimized Formulation
3.9. In-Vitro Cytotoxicity Study of the CLX-IPP Optimized Formula Using MTT-Assay
3.10. Pharmacokinetic Analysis of the Optimized CLX-IPP Formula Compared to Market Product in Rabbits
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Independent Variables | Low | Mid | High |
---|---|---|---|
X1: Amount of Lipid | 200 | 400 | 600 |
X2: Amount of Surfactant | 200 | 300 | 400 |
Dependent Variables (Responses) | Desirability Constrains | ||
Y1: Particle size (PS) | Minimize | ||
Y2: Entrapment Efficiency (EE) % | Maximize |
Formula | Celecoxib Amount (mg) | Cetyl Alcohol Amount (mg) | Span 40 Amount (mg) | Spray Dried Lactose Amount (mg) |
---|---|---|---|---|
F1 | 200 | 200 | 200 | 1500 |
F2 | 200 | 300 | 200 | 1500 |
F3 | 200 | 400 | 200 | 1500 |
F4 | 200 | 200 | 400 | 1500 |
F5 | 200 | 300 | 400 | 1500 |
F6 | 200 | 400 | 400 | 1500 |
F7 | 200 | 200 | 600 | 1500 |
F8 | 200 | 300 | 600 | 1500 |
F9 | 200 | 400 | 600 | 1500 |
Formula | P.S | PDI | ZP | EE % |
---|---|---|---|---|
F1 | 621.2 ± 2.82 | 0.494 ± 0.019 | −36.1 ± 0.67 | 92.67 ± 0.75 |
F2 | 522.5 ± 3.86 | 0.348 ± 0.047 | −40.1 ± 0.96 | 94.51 ± 1.25 |
F3 | 461.0 ± 2.35 | 0.318 ± 0.011 | −37.1 ± 1.36 | 88.56 ± 0.95 |
F4 | 447.5 ± 5.33 | 0.375 ± 0.007 | −37.9 ± 1.32 | 91.50 ± 2.21 |
F5 | 520.1 ± 1.32 | 0.404 ± 0.023 | −38.9 ± 1.72 | 92.49 ± 2.08 |
F6 | 429.4 ± 2.47 | 0.312 ± 0.033 | −38.8 ± 1.33 | 97.39 ± 1.58 |
F7 | 381.8 ± 3.90 | 0.481 ± 0.072 | −36.8 ± 1.78 | 95.61 ± 1.86 |
F8 | 389.4 ± 2.53 | 0.466 ± 0.025 | −39.3 ± 0.75 | 95.20 ± 2.24 |
F9 | 351.7 ± 1.76 | 0.302 ± 0.046 | −41.3 ± 0.90 | 97.53 ± 0.84 |
Parameter | Celebrex 100 mg Caps | Opt. CLX-IPP |
---|---|---|
Cmax (µg/mL) | 1.91 ± 0.15 | 2.38 * ± 0.22 |
AUC0–24 (h·µg/mL) | 15.968 ± 2.18 | 35.748 * ± 3.01 |
Tmax (h) | 4 | 6 * |
T1/2 (h) | 6.186 ± 0.17 | 14 * ± 0.25 |
Kel (h−1) | 0.112 ± 0.018 | 0.0495 * ± 0.023 |
MRT (h) | 9.509 ± 0.24 | 12.147 * ± 0.19 |
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Nasr, A.M.; Elhady, S.S.; Swidan, S.A.; Badawi, N.M. Celecoxib Loaded In-Situ Provesicular Powder and Its In-Vitro Cytotoxic Effect for Cancer Therapy: Fabrication, Characterization, Optimization and Pharmacokinetic Evaluation. Pharmaceutics 2020, 12, 1157. https://doi.org/10.3390/pharmaceutics12121157
Nasr AM, Elhady SS, Swidan SA, Badawi NM. Celecoxib Loaded In-Situ Provesicular Powder and Its In-Vitro Cytotoxic Effect for Cancer Therapy: Fabrication, Characterization, Optimization and Pharmacokinetic Evaluation. Pharmaceutics. 2020; 12(12):1157. https://doi.org/10.3390/pharmaceutics12121157
Chicago/Turabian StyleNasr, Ali M., Sameh S. Elhady, Shady A. Swidan, and Noha M. Badawi. 2020. "Celecoxib Loaded In-Situ Provesicular Powder and Its In-Vitro Cytotoxic Effect for Cancer Therapy: Fabrication, Characterization, Optimization and Pharmacokinetic Evaluation" Pharmaceutics 12, no. 12: 1157. https://doi.org/10.3390/pharmaceutics12121157