In Vitro Approaches to Explore the Anticancer Potential of One Natural Flavanone and Four Derivatives Loaded in Biopolymeric Nanoparticles for Application in Topical Delivery Treatments
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. In Silico Analyses
2.3. Poly DL-Lactide-Co-Glycolide Acid (PLGA) Nanoparticles (NPs)
2.4. Chromatographic Operating Conditions
2.5. Cytotoxicity Assays: Cell Culture and Cell Viability Assays
2.6. Structure–Activity Relationship Study (SAR)
2.7. Ex Vivo Studies
2.8. Data Analyses
3. Results
3.1. In Silico Analyses
3.2. Cytotoxicity Activity
3.3. Structure–Activity Relationship Study (SAR)
3.4. Ex Vivo Studies
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nanoparticle | Physicochemical Characteristics | |||
---|---|---|---|---|
Z-Average (nm) | PI | Z (mV) | EE (%) | |
NP 1 | 205.20 ± 0.27 | 0.06 ± 0.05 | −8.25 ± 0.24 | 80.00 ± 4.75 |
NP 1a | 178.03 ± 1.33 | 0.08 ± 0.004 | −9.05 ± 0.32 | 88.47 ± 4.18 |
NP 1b | 141.63 ± 0.78 | 0.09 ± 0.02 | −10.63 ± 0.23 | 85.00 ± 5.80 |
NP 1c | 175.17 ± 0.60 | 0.10 ± 0.03 | −6.48 ± 0.38 | 78.28 ± 5.85 |
NP 1d | 173.40 ± 1.59 | 0.06 ± 0.01 | −6.65 ± 0.41 | 78.75 ± 4.34 |
Data | Flavanone | ||||
---|---|---|---|---|---|
1 | 1a | 1b | 1c | 1d | |
Anticarcinogenic (Pa) | 0.790 | 0.768 | 0.797 | 0.722 | 0.625 |
Antineoplastic (Pa) | 0.774 | 0.804 | 0.758 | 0.692 | 0.797 |
MMP-9 | 0.734 | 0.588 | 0.766 | 0.481 | 0.523 |
Caspase-3 | 0.423 | 0.648 | 0.604 | 0.318 | 0.330 |
Caspase-8 | 0.256 | 0.297 | 0.279 | ND | 0.259 |
Telomerase | 0.136 | ND | 0.116 | 0.083 | 0.121 |
Inteleukine-6 | 0.192 | 0.171 | 0.179 | ND | 0.164 |
Interleukine-10 | ND | ND | 0.095 | 0.096 | 0.099 |
Compound | Cell Line | NPs | Cell Line | |||
---|---|---|---|---|---|---|
HEK-293 | M21 | HeLa | M21 | HeLa | ||
IC50 (µM) | IC50 (µM) | |||||
1 | 6.59 | 7.37 | 24.05 | NP 1 | 49.72 | 11.19 |
1a | 28.1 | 20.88 | 19.53 | NP 1a | 10.28 | 36.73 |
1b | 22.10 | 13.29 | 11.14 | NP 1b | 14.28 | 10.89 |
1c | 27.21 | 21.18 | 19.09 | NP 1c | NE | NE |
1d | 28.28 | 15.77 | 12.81 | NP 1d | 49.71 | 24.84 |
Physicochemical Properties | Flavanones | ||||
---|---|---|---|---|---|
1 | 1a | 1b | 1c | 1d | |
Total energy (kcal/mol) | −94,946.90 | −12,2792.00 | −98,527.20 | −94,951.30 | −94,294.20 |
Binding energy (kcal/mol) | −4809.71 | −5879.46 | −5078.27 | −4814.19 | −4682.68 |
Heat of formation (kcal/mol) | −111.63 | −170.30 | −105.10 | −116.11 | −88.81 |
Surface area (A2) | 577.35 | 680.43 | 607.10 | 538.39 | 549.13 |
Volume (A3) | 959.56 | 1176.83 | 1014.63 | 913.85 | 917.78 |
Mass (amu) | 324.48 | 408.40 | 338.40 | 324.38 | 322.36 |
HOMO (eV) | −9.02 | −9.11 | −8.95 | −8.98 | −8.67 |
LUMO (eV) | −0.56 | −0.65 | −0.50 | −0.40 | −0.54 |
Log P | 0.70 | 0.26 | 0.73 | 0.05 | −0.07 |
Dipole moment (µ) | 3.55 | 1.50 | 3.82 | 1.44 | 1.52 |
Polarizability (α) | 35.81 | 43.32 | 37.64 | 35.22 | 35.03 |
Molecular Descriptors | Free Flavanones | NPs Flavanones | ||||||
---|---|---|---|---|---|---|---|---|
M21 | HeLa | M21 | HeLa | |||||
r2 | F | r2 | F | r2 | F | r2 | F | |
ET, EE, EF | 0.99 | 10.98 | 0.94 | 2.57 | 0.99 | 13.09 | 0.97 | 6.07 |
HOMO, LUMO | 0.26 | 0.07 | 0.18 | 0.03 | 0.39 | 0.18 | 0.62 | 0.64 |
A, V, MM | 0.58 | 0.17 | 0.85 | 0.84 | 0.94 | 2.52 | 0.99 | 12.71 |
Log P, α, μ | 0.46 | 0.28 | 0.89 | 1.24 | 0.98 | 6.77 | 0.99 | 36.75 |
NP 1 * | NP 1a | NP 1b | NP 1c | NP 1d | |
---|---|---|---|---|---|
J/sur (μg/h/cm2) | |||||
0.35 | 160.98 | 0.03 | 0.54 | 2.37 | |
(0.53−0.005) | (183.52–138.39) | (0.038–0.022) | (0.61–0.49) | (2.71–2.02) | |
Qr (g/gskin/cm2) | |||||
0.54 | 1.44 | 0.07 | 0.04 | 0.01 | |
(0.62–0.46) | (1.66–1.22) | (0.08–0.06) | (0.05–0.03) | (0.006–0.004) | |
Qp (µg) | |||||
30.34 | 78.08 | 17.84 | 43.32 | 118.29 | |
(34.13–26.55) | (90.81–65.35) | (20.29–15.40) | (50.12–36.52) | (132.49–104.10) |
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Bustos-Salgado, P.; Andrade-Carrera, B.; Domínguez-Villegas, V.; Noé, V.; Mallandrich, M.; Colom, H.; Calpena-Campmany, A.; Garduño-Ramírez, M.L. In Vitro Approaches to Explore the Anticancer Potential of One Natural Flavanone and Four Derivatives Loaded in Biopolymeric Nanoparticles for Application in Topical Delivery Treatments. Pharmaceutics 2023, 15, 1632. https://doi.org/10.3390/pharmaceutics15061632
Bustos-Salgado P, Andrade-Carrera B, Domínguez-Villegas V, Noé V, Mallandrich M, Colom H, Calpena-Campmany A, Garduño-Ramírez ML. In Vitro Approaches to Explore the Anticancer Potential of One Natural Flavanone and Four Derivatives Loaded in Biopolymeric Nanoparticles for Application in Topical Delivery Treatments. Pharmaceutics. 2023; 15(6):1632. https://doi.org/10.3390/pharmaceutics15061632
Chicago/Turabian StyleBustos-Salgado, Paola, Berenice Andrade-Carrera, Valeri Domínguez-Villegas, Véronique Noé, Mireia Mallandrich, Helena Colom, Ana Calpena-Campmany, and María Luisa Garduño-Ramírez. 2023. "In Vitro Approaches to Explore the Anticancer Potential of One Natural Flavanone and Four Derivatives Loaded in Biopolymeric Nanoparticles for Application in Topical Delivery Treatments" Pharmaceutics 15, no. 6: 1632. https://doi.org/10.3390/pharmaceutics15061632
APA StyleBustos-Salgado, P., Andrade-Carrera, B., Domínguez-Villegas, V., Noé, V., Mallandrich, M., Colom, H., Calpena-Campmany, A., & Garduño-Ramírez, M. L. (2023). In Vitro Approaches to Explore the Anticancer Potential of One Natural Flavanone and Four Derivatives Loaded in Biopolymeric Nanoparticles for Application in Topical Delivery Treatments. Pharmaceutics, 15(6), 1632. https://doi.org/10.3390/pharmaceutics15061632