Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate Cancer Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Nanoparticles
Optimization by Design of Experiments
2.3. Particle Size, Polydispersity Index, and Zeta Potential Analysis Using Dynamic Light Scattering
2.4. Determination of Folic Acid Content by Ultra-Violet (UV) Spectrophotometry
2.5. Characterization Using Fourier Transform Infra-Red (FTIR)
2.6. Investigation of Thermal Degradation by Thermogravimetric Analysis (TGA)
2.7. Surface and Crystallinity Experiments Using Powder X-Ray Diffraction (XRD)
2.8. Phase Transition Studies Employing Differential Scanning Calorimetry (DSC)
2.9. Scanning Electron Microscopy (SEM) of Sample Suspensions
2.10. UV Spectrophotometric Analysis of Quercetin Loading in Nanoparticle Systems
2.11. In Vitro Release of Quercetin
2.12. Cell Culture Conditions and Cytotoxicity Studies
2.13. Cellular Uptake of Nanoparticles
2.14. Statistical Analysis
3. Results
3.1. Optimized Formulation Results Using DOE
3.1.1. Quercetin Loading, Size, and Potential and Folic Acid Conjugation of Formulations
3.1.2. Analysis of Responses
Effects of the Interaction between the Quercetin and Chitosan Factors
3.2. Size and Potential Data Show Spherical Coated Particles with Positive Surface Charge
3.3. Molecular Structure by FTIR Shows Adsorption Interactions and XRD Show Amorphous Nanoparticle Structure
3.4. Thermal Degradation and Phase Transition Show Retention of Polymer Properties
3.5. In Vitro Kinetic Study of Nanoparticle Systems Shows Efficient Quercetin Release
3.6. Increased Cytotoxicity of Quercetin in Nanoparticle System
3.7. Greater Cellular Uptake of Targeted Nanoparticles in a PSMA-Positive Cell Line
4. Discussion
5. 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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Formulation | Parameters | Q/mg | Chi/mg | Fol/mg |
---|---|---|---|---|
P1 | (1, 0, 0) | 30 | 35 | 30 |
P2 | (−1, −1, −1) | 10 | 10 | 15 |
P3 | (0, 0, −1) | 20 | 35 | 10 |
P4 | (1, 1, 1) | 30 | 60 | 45 |
P5 | (0, 0, 0) | 20 | 35 | 30 |
P6 | (0, 1, 0) | 20 | 60 | 30 |
P7 | (−1, 1, −1) | 10 | 60 | 15 |
P8 | (1, 1, −1) | 30 | 60 | 15 |
P9 | (1, −1, −1) | 30 | 10 | 15 |
P10 | (1, −1, 1) | 30 | 10 | 45 |
P11 | (0, −1, 0) | 20 | 10 | 30 |
P12 | (0, 0, 0) | 20 | 35 | 30 |
P13 | (−1, −1, 1) | 10 | 10 | 45 |
P14 | (0, 0, 1) | 20 | 35 | 45 |
P15 | (−1, 1, 1) | 10 | 60 | 45 |
P16 | (−1, 0, 0) | 10 | 35 | 30 |
Formulation | Parameters | QL/% | Ζ Potential | FA/% |
---|---|---|---|---|
P1 | (1, 0, 0) | 9.04 ± 2.15 | −1.60 ± 1.45 | 1.90 ± 0.15 |
P2 | (−1, −1, −1) | 3.01 ± 1.50 | +2.33 ± 0.87 | 0.37 ± 0.15 |
P3 | (0, 0, −1) | 3.90 ± 1.05 | +2.40 ± 0.08 | 0.77 ± 0.26 |
P4 | (1, 1, 1) | 8.27 ± 1.30 | −5.03 ± 0.67 | 1.20 ± 0.25 |
P5 | (0, 0, 0) | 2.78 ± 1.71 | +3.79 ± 1.21 | 0.44 ± 0.06 |
P6 | (0, 1, 0) | 1.83 ± 1.30 | −2.17 ± 0.63 | 0.21 ± 0.17 |
P7 | (−1, 1, −1) | 1.71 ± 2.86 | +3.83 ± 1.34 | 0.18 ± 0.15 |
P8 | (1, 1, −1) | 6.72 ± 1.30 | −4.93 ± 0.17 | 0.66 ± 0.46 |
P9 | (1, −1, −1) | 8.94 ± 1.30 | +1.07 ± 0.35 | 0.91 ± 0.10 |
P10 | (1, −1, 1) | 14.2 ± 2.39 | −3.37 ± 0.31 | 1.48 ± 0,59 |
P11 | (0, −1, 0) | 5.18 ± 0.80 | +1.58 ± 1.56 | 0.61 ± 0.21 |
P12 | (0, 0, 0) | 2.45 ± 1.67 | +3.15 ± 0,47 | 0.54 ± 0.17 |
P13 | (−1, −1, 1) | 7.01 ± 1.05 | −1.20 ± 0.61 | 0.95 ± 0.25 |
P14 | (0, 0, 1) | 6.12 ± 1.30 | +2.39 ± 0.85 | 1.13 ± 0.21 |
P15 | (−1, 1, 1) | 6.05 ± 0.80 | +3.28 ± 0.36 | 0.95 ± 0.15 |
P16 | (−1, 0, 0) | 3.42 ± 1.30 | +2.26 ± 0.29 | 0.70 ± 0.25 |
Response | Predicted | Actual | Bias |
---|---|---|---|
Quercetin Loading | 7.02 | 7.11 ± 1.60 | +0.0126 |
Surface Charge | +2.52 | +1.84 ± 0.40 | −0.370 |
Folic Acid Content | 1.24 | 1.61 ± 0.35 | +0.236 |
Formulation | Size/nm | PDI | ζ Potential/mV |
---|---|---|---|
Uncoated nps | 159.8 ± 2.0 | 0.068 ± 0.01 | −21.0 ± 1.6 |
Coated nps | 206.2 ± 1.7 | 0.069 ± 0.002 | +1.84 ± 0.4 |
Cell Line | Treatment | % Fluorescence |
---|---|---|
LnCap | Coated nps | 2.79 ± 0.50 |
PC-3 | Uncoated nps | 1.86 ± 0.22 |
Coated nps | 1.72 ± 0.37 | |
Uncoated nps | 1.99 ± 0.39 |
System | ζ Potential/mV | Drug Release | Biological Activity |
---|---|---|---|
Silica nanoparticles | Varied | 7% after 72 h | Not specified |
Pegylated quercetin liposomes | −13.1 | 85% after 96 h | Increased cytotoxicity in cervical cancer cells and greater reduction in tumor size in a mouse model compared to free quercetin |
Nanomicelles | Not specified | 83.6% after 120 h | Increased cytotoxicity on breast cancer cells compared to free quercetin |
Chitosan-quercetin nps | +22.53 | 76% after 12 h | Increased cytotoxicity on lung and breast cancer cells and greater reduction in tumor volume in a mouse model compared to free quercetin |
SPIONS | Varied | Not applicable | Increased protein binding of positively charged particles |
Chitosan nps | +9 | 100% after 24 h | Not specified |
Folate-linked nps | +19 | 70% after 4 h | PSMA binding on LnCap cells |
Folic acid-conjugated nps | Not specified | 90% after 24 h | Increased cytotoxicity of therapeutic peptide and greater cellular uptake in LnCap cells |
Folic acid minicells | Not specified | Not applicable | Increased cellular uptake in LnCap cells |
PLGA-quercetin chitosan folic acid nps | +1.84 | 78% after 168 h | Increased cytotoxicity of quercetin and greater cellular uptake in LnCap cells |
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Share and Cite
Essa, D.; Kondiah, P.P.D.; Kumar, P.; Choonara, Y.E. Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate Cancer Cells. Biomedicines 2023, 11, 1201. https://doi.org/10.3390/biomedicines11041201
Essa D, Kondiah PPD, Kumar P, Choonara YE. Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate Cancer Cells. Biomedicines. 2023; 11(4):1201. https://doi.org/10.3390/biomedicines11041201
Chicago/Turabian StyleEssa, Divesha, Pierre P. D. Kondiah, Pradeep Kumar, and Yahya E. Choonara. 2023. "Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate Cancer Cells" Biomedicines 11, no. 4: 1201. https://doi.org/10.3390/biomedicines11041201
APA StyleEssa, D., Kondiah, P. P. D., Kumar, P., & Choonara, Y. E. (2023). Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate Cancer Cells. Biomedicines, 11(4), 1201. https://doi.org/10.3390/biomedicines11041201