An Experimental Design Approach for Producing Curcumin-Loaded Solid Lipid Nanoparticles
Abstract
:1. Introduction
2. Results
2.1. Saturation Solubility Study
2.2. Preliminary Study
2.3. Experimental Design
2.4. Morphological Analysis
2.5. In Vitro Release Study
2.6. Short-Term Stability
2.7. Cell Viability
2.8. Cellular Internalization
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Determination Method for Curcumin
4.3. Saturation Solubility Study
4.4. Determination of Parameters: Preliminary Study
4.5. Preparation of SLNs
4.6. Design of Experiments
4.7. Particle Size and Zeta Potential Measurements
4.8. Encapsulation Efficiency
4.9. Morphological Analysis
4.10. In Vitro Release Study
4.11. Short-Term Stability
4.12. In Vitro Cell Viability Assay
4.13. Confocal Laser Scanning Microscopy (CLSM)
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
SLN | Solid lipid nanoparticle |
TEA | Triethanol amine |
Benz. Ch. | Benzalkonium chloride |
Na-Tau | Sodium taurocholate |
SLS | Sodium lauryl sulfate |
βCDSE | β cyclodextrine sulfobutyl ethers |
PG | Propylene glycol |
OD | Octyldodecanol |
MCE12 | Macrogol cetostrearyl ether 12 |
MCE20 | Macrogol setotrearil ether 20 |
DoE | Design of experiment |
CCD | Central composite design |
2D | 2-dimensional |
3D | 3-dimensional |
PS | Particle diameter |
PI | Polydispersity index |
EE | Encapsulation efficiency |
CLSM | Confocal Laser Scanning Microscopy |
HLB | Hydrophilic–lipophilic balance |
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Run | Critical Factors | Response Variables | |||||
---|---|---|---|---|---|---|---|
X1 | X2 | X3 | PS (nm) | ZP (mV) | EE% | DL% | |
1 | −1 | −1 | −1 | 287.9 ± 9.8 | −17.3 ± 1 | 29.66 ± 1.92 | 0.15 ± 0.01 |
2 | −1 | 1 | −1 | 201.7 ± 13.5 | −15.9 ± 0.9 | 10.73 ± 2.06 | 0.05 ± 0.01 |
3 | 1 | −1 | −1 | 236.9 ± 8.8 | −18.3 ± 0.4 | 19.38 ± 1.53 | 0.29 ± 0.02 |
4 | 1 | 1 | −1 | 398.0 ± 27.4 | −10.7 ± 0.9 | 13.28 ± 1.58 | 0.20 ± 0.02 |
5 | −1 | −1 | 1 | 424.9 ± 14.8 | −36.1 ± 2.1 | 10.07 ± 2.07 | 0.05 ± 0.01 |
6 | −1 | 1 | 1 | 340.4 ± 13.8 | −16.7 ± 0.8 | 28.02 ± 1.93 | 0.14 ± 0.01 |
7 | 1 | −1 | 1 | 656.2 ± 21.0 | −39.0 ± 2.6 | 23.02 ± 1.05 | 0.34 ± 0.02 |
8 | 1 | 1 | 1 | 512.3 ± 33.4 | −31.8 ± 1.4 | 23.95 ± 1.47 | 0.36 ± 0.02 |
9 | 0 | −1 | 0 | 929.5 ± 50.9 | −31.5 ± 2.4 | 24.85 ± 1.26 | 0.25 ± 0.01 |
10 | 0 | 1 | 0 | 999.6 ± 51.2 | −30.2 ± 1.1 | 21.74 ± 1.29 | 0.22 ± 0.01 |
11 | −1 | 0 | 0 | 780.0 ± 33.2 | −30.6 ± 1.1 | 24.90 ± 0.60 | 0.12 ± 0.01 |
12 | 1 | 0 | 0 | 509.2 ± 27.3 | −21.9 ± 1.6 | 28.36 ± 1.01 | 0.42 ± 0.02 |
13 | 0 | 0 | −1 | 364.8 ± 9.7 | −24.1 ± 1.1 | 28.11 ± 1.24 | 0.28 ± 0.01 |
14 | 0 | 0 | 1 | 507.2 ± 20.7 | −22.5 ± 1.1 | 28.76 ± 1.23 | 0.29 ± 0.01 |
15 | 0 | 0 | 0 | 354.1 ± 44.5 | −17.8 ± 4.1 | 34.31 ± 1.19 | 0.34 ± 0.01 |
16 | 0 | 0 | 0 | 356.3 ± 10.8 | −23.7 ± 1.0 | 33.33 ± 1.20 | 0.33 ± 0.01 |
17 | 0 | 0 | 0 | 339.5 ± 7.4 | −25.2 ± 1.4 | 20.60 ± 1.30 | 0.21 ± 0.01 |
Coefficients | |||||
---|---|---|---|---|---|
ZP (mV) | PS (nm) | EE% | DL% | ||
bo | Constant | −25.097 ** | 603.585 ** | 29.361 ** | 0.295 ** |
b1 | Curcumin (mg) | 3.690 | −8.340 | −0.926 | −0.011 |
b2 | Surfactant (%) | −0.510 | 27.770 | 0.461 | 0.110 ** |
b3 | Stirring (rpm) | −5.980 * | 95.170 | 1.266 | 0.021 |
b1 × b1 | Cur × Cur | −3.605 | 220.752 | −6.027 | −0.061 |
b2 × b2 | Sur × Sur | 0.995 | −99.198 | −2.692 | −0.026 |
b3 × b3 | Stir × Stir | 3.945 | −307.798 | −0.887 | −0.011 |
b1 × b2 | Cur × Sur | −0.750 | 23.488 | −0.524 | −0.008 |
b1 × b3 | Cur × Stir | 2.200 | −37.913 | 5.489 * | 0.038 |
b2 × b3 | Sur × Stir | −2.775 | 32.238 | 2.076 | 0.028 |
PS (nm) | ZP (mV) | EE (%) | DL (%) | |
---|---|---|---|---|
Optimum formulation | 389.31 ± 9.95 | −27.50 ± 0.80 | 28.95 ± 4.36 | 0.27 ± 0.03 |
Calculated | 369.66 | −30.85 | 28.28 | 0.41 |
Drug | r2 | e | Intercept | |
---|---|---|---|---|
0th-order kinetics | Free | 0.658 | 3 | 20.723 |
Loaded | 0.915 | 7.080 | ||
1st-order kinetics | Free | 0.325 | 88 | 2.243 |
Loaded | 0.430 | 1.592 | ||
Higuchi | Free | 0.799 | 70 | 2.534 |
Loaded | 0.962 | −8.108 | ||
Korsmeyer–Peppas | Free | 0.842 | 87 | 2.089 |
Loaded | 0.743 | 1.248 |
Independent Factors | Level Used | ||
---|---|---|---|
−1 | 0 | +1 | |
X1: The amount of curcumin (mg) | 2.5 | 5 | 7.5 |
X2: The ratio of surfactants (Brij–Gelucire) | 400:0 | 200:200 | 300:100 |
X3: The stirring speed (rpm) | 500 | 700 | 1000 |
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Saka, O.M.; Aygüler, C.İ.; Özdemir, N.S.; Sürücü, B.; Çakırlı, E.; Nemutlu, E.; Demirbolat, G.M. An Experimental Design Approach for Producing Curcumin-Loaded Solid Lipid Nanoparticles. Pharmaceuticals 2025, 18, 470. https://doi.org/10.3390/ph18040470
Saka OM, Aygüler Cİ, Özdemir NS, Sürücü B, Çakırlı E, Nemutlu E, Demirbolat GM. An Experimental Design Approach for Producing Curcumin-Loaded Solid Lipid Nanoparticles. Pharmaceuticals. 2025; 18(4):470. https://doi.org/10.3390/ph18040470
Chicago/Turabian StyleSaka, Ongun Mehmet, Cemre İrem Aygüler, Neval Sevinç Özdemir, Bilge Sürücü, Egemen Çakırlı, Emirhan Nemutlu, and Gülen Melike Demirbolat. 2025. "An Experimental Design Approach for Producing Curcumin-Loaded Solid Lipid Nanoparticles" Pharmaceuticals 18, no. 4: 470. https://doi.org/10.3390/ph18040470
APA StyleSaka, O. M., Aygüler, C. İ., Özdemir, N. S., Sürücü, B., Çakırlı, E., Nemutlu, E., & Demirbolat, G. M. (2025). An Experimental Design Approach for Producing Curcumin-Loaded Solid Lipid Nanoparticles. Pharmaceuticals, 18(4), 470. https://doi.org/10.3390/ph18040470