Pullulan/Poly(vinyl alcohol) Hydrogels Loaded with Calendula officinalis Extract: Design and In Vitro Evaluation for Wound Healing Applications
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of Pristine P/PVA Hydrogels
2.3. Preparation of Calendula Extract—Loaded P/PVA Hydrogels
2.4. Characterization of Calendula officinalis Extract
2.4.1. Identification of Phenolic and Triterpenic Compounds by HPLC-ESI MS
2.4.2. Total Phenolic Content (TPC)
2.4.3. Total Flavonoid Content (TFC)
2.4.4. Total Triterpenes Content (TTPC)
2.5. Characterization of Unloaded and Calendula-Extract-Loaded P/PVA Hydrogels
2.5.1. Chemical Composition
2.5.2. Morphology and Porosity
2.5.3. Swelling Ratio
2.5.4. Mechanical Properties and Bioadhesiveness
2.6. Loading Capacity and Calendula Extract Release from Hydrogels
2.7. Antioxidant Activity
2.8. Antibacterial Activity
2.9. Cytotoxic Activity
2.10. Statistical Analysis
3. Results and Discussion
3.1. Characterization of Calendula officinalis Extract
3.2. Synthesis of P/PVA Hydrogels
3.3. Loading of P/PVA Hydrogels
3.3.1. FT-IR Spectra
3.3.2. Morphology and Pore Size
3.3.3. Swelling Behavior
3.3.4. Mechanical Properties and Bioadhesiveness
3.4. Release Kinetic of Calendula officinalis from P/PVA Hydrogels
3.5. Antioxidant Activity
3.6. Antibacterial Activity
3.7. Cytotoxic Activity
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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No. | Identified Compound | RT (min) | Column/ Ionization Mode | Major ESI m/z Observed | Ref. |
---|---|---|---|---|---|
1 | Chlorogenic acid | 9.23 24.34 | Phenomenex C18 Luna/ESI(−) Mediterranea Sea 18/ESI(+) | 707.22 [2M-H]− 353.11 [M-H]− 191.06 [QA-H]− 355.31 [M+H]+ 163.14 [M-QA]+ | [53,54,55] |
2 | Caffeic acid | 11.35 | Phenomenex C18 Luna/ESI(−) | 179.04 [M-H]− 135.05 [M-CO2]− | [59] |
3 | Quercitin-3-O-rhamnosylrutinoside | 13.32 | Phenomenex C18 Luna/ESI(−) | 1511.46 [2M-H]− 755.24 [M-H]− | [59,60] |
4 | Typhaneoside | 14.77 42.50 | Phenomenex C18 Luna/ESI(−) Mediterranea Sea 18/ESI(+) | 769.25 [M-H]− 771.162 [M+H]+ 625.35 [M-Rham+H]+ | [57,58] |
5 | Quercitin-3-O-rutinoside | 15.75 39.68 | Phenomenex C18 Luna/ESI(−) Mediterranea Sea 18/ESI(+) | 1219.34 [2M-H]− 609.18 [M-H]− 611.34 [M+H]+ 465.32 [M-Rham+H]+ | [59,60] |
6 | Isorhamnetin 3-O-rutinoside | 16.55 43.22 | Phenomenex C18 Luna/ESI(−) Mediterranea Sea 18/ESI(+) | 1247.37 [2M-H]− 623.20 [M-H]− 625.35 [M+H]+ 479.33 [M-Rham+H]+ | [59,60,62] |
7 | Quercetin-3-O-galactoside | 16.55 45.32 | Phenomenex C18 Luna/ESI(−) Mediterranea Sea 18/ESI(+) | 927.22 [2M-H]− 463.11 [M-H]− 301.12 [M-Glu-H]− 465.32 [M+H]+ | [60,61] |
8 | Quercitin-3-O-rutinoside isomer | 17.32 | Phenomenex C18 Luna/ESI(−) | 1219.34 [2M-H]− 609.17 [M-H]− | [59,60] |
9 | Caffeic acid 3-glucoside | 17.58 | Mediterranea Sea 18/ESI(+) | 343.54 [M+H]+ 181.15 [M-Glu+H]+ | [53,54,55] |
10 | Isorhamnetin rutinoside | 18.01 | Phenomenex C18 Luna/ESI(−) | 1247.37 [2M-H]− 623.20 [M-H]− | [60,62] |
11 | Dicaffeoylquinic acid | 18.43 | Phenomenex C18 Luna/ESI(−) | 515.14 [M-H]− | [61,62] |
12 | Isorhamnetin-3-O-glucoside | 18.97 49.93 | Phenomenex C18 Luna/ESI(−) Mediterranea Sea 18/ESI(+) | 955.25 [2M-H]− 477.12 [M-H]− 479.32 [M+H]+ | [56,59,60,62] |
13 | Hydroxycaffeic acid | 34.28 | Mediterranea Sea 18/ESI(+) | 197.26 [M+H]+ 179.13 [M-OH]+ | [53,54,55] |
14 | Dicaffeoylquinic acid | 18.43 | Phenomenex C18 Luna/ESI(−) | 515.14 [M-H]− 353.10 [CGA-H]− | [61,62] |
15 | Isorhamnetin 3,7-di-O-β-D-glucopyranoside | 46.22 | Mediterranea Sea 18/ESI(+) | 641.513 M+H]+ | [53,54,55] |
16 | Oleanolic acid glucuronide A | 26.40 | Phenomenex C18 Luna/ESI(−) | 1117.57 [M-H]− 793 [M-H-2Hex]− | [52,60,63] |
17 | Oleanolic acid glucuronide A isomer | 29.39 | Phenomenex C18 Luna/ESI(−) | 1117.56 [M-H]− 581.29 [M-H-2Hex-HexUA]− | [52,63,64] |
18 | Oleanolic acid glucuronide C | 30.28 | Phenomenex C18 Luna/ESI(−) | 955.50 [M-H]− 500.26 [M-OA]− | [52,63] |
19 | Oleanolic acid glucuronide D | 30.75 | Phenomenex C18 Luna/ESI(−) | 793.46 [M-H]− 569 [M-H-Hex-H2O-CO2]− | [52] |
TPC (mg GAE/g) | TFC (mg QE/g) | TTPC (mg OAE/g) | DPPH, IC50 (μg/mL) | ||
---|---|---|---|---|---|
C. officinalis Extract | Ascorbic Acid | Quercetin | |||
15.03 ± 0.45 | 79.42 ± 2.92 | 53.58 ± 0.47 | 122.67 ± 4.5 | 3.1 ± 0.12 | 2.3 ± 0.14 |
Sample Code | Initial Mixture | Final Composition | |||||
---|---|---|---|---|---|---|---|
P/PVA Ratio (%, w/w) | STMP/(P + PVA) Ratio (w/w) | NaOH/(P + PVA) Ratio (w/w) | GF * (%, w/w) | P (%, w/w) | PVA (%, w/w) | PO42− Content ** (meq./g) | |
H #0 | 25/75 | 0.125/1 | 0.1/1 | 65.44 ± 3.9 | 36.08 ± 2.45 | 63.92 ± 2.45 | 0.74 ± 0.06 |
Sample Code | C. officinalis Conc. (%, w/v) | Gravimetric Ratio Extract/H (w/w) | LC (mg C. officinalis/g H) | TPC (mg GAE/g H) | TTPC (mg OAE/g H) |
---|---|---|---|---|---|
H #1 | 5 | 1/1 | 211.4 ± 8.9 | 10.02 ± 0.73 | 9.98 ± 0.78 |
H #2 | 10 | 334.4 ± 4.6 | 14.36 ± 1.09 | 12.18 ± 1.07 | |
H #3 | 20 | 736.7 ± 2.1 | 24.33 ± 1.04 | 22.87 ± 1.11 |
Sample Code | Young’s Modulus (KPa) | Compressive Strength (KPa) | Maximal Adhesive Force Fmax (N) |
---|---|---|---|
H #0 | 42.53 ± 5.22 | 61.67 ± 6.47 | 0.37 ± 0.04 |
H #1 | 78.87 ± 3.40 b | 81.75 ± 3.44 a | 0.38 ± 0.04 |
H #2 | 69.06 ± 1.13 b | 76.25 ± 2.97 | 0.43 ± 0.02 a |
H #3 | 47.56 ± 4.80 | 66.33 ± 3.60 | 0.56 ± 0.03 |
Mean Value and Standard Deviation of the Inhibition Zones (mm) * | |||||
---|---|---|---|---|---|
Species | C (+) | C (−) | H #1 | H #2 | H #3 |
C. officinalis Extract Content (mg) | |||||
0 | 2.1 | 3.9 | 10.5 | ||
S. aureus ATCC25923 | 22 | 5 | 11 ± 0.3 | 12 ± 0.25 | 13 ± 0.35 |
Escherichia coli ATCC 25922 | 24 | 5 | 11.5 ± 0.1 | 11.6 ± 0.4 | 12 ± 0.5 |
P. aeruginosa 9027 ATCC | 22 | 5 | 5 ± 0.1 | 5 ± 0.2 | 15 ± 0.1 |
C. albicans ATCC 90028 | 16 | 5 | 6 ± 0.25 | 7 ± 0.3 | 8 ± 0.4 |
Time (h) | Sample | Log Reduction/% Reduction | ||||
---|---|---|---|---|---|---|
Species | S. aureus | E. coli | P. aeruginosa | C. albicans | ||
24 | H #1 | 4.87/100 | 4.87/100 | 2.96/99.89 | 3.92/99.98 | |
H #2 | 4.87/100 | 4.87/100 | 3.20/99.94 | 4.87/100 | ||
H #3 | 4.87/100 | 4.87/100 | 4.87/100 | 4.87/100 | ||
72 | H #1 | 4.87/100 | 2.17/99.33 | 2.39/99.59 | 2.95/99.88 | |
H #2 | 4.57/99.99 | 2.37/99.58 | 2.53/99.70 | 2.98/99.89 | ||
H #3 | 4.57/99.99 | 4.57/99.99 | 4.57/99.99 | 4.87/100 |
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Pelin, I.M.; Silion, M.; Popescu, I.; Rîmbu, C.M.; Fundueanu, G.; Constantin, M. Pullulan/Poly(vinyl alcohol) Hydrogels Loaded with Calendula officinalis Extract: Design and In Vitro Evaluation for Wound Healing Applications. Pharmaceutics 2023, 15, 1674. https://doi.org/10.3390/pharmaceutics15061674
Pelin IM, Silion M, Popescu I, Rîmbu CM, Fundueanu G, Constantin M. Pullulan/Poly(vinyl alcohol) Hydrogels Loaded with Calendula officinalis Extract: Design and In Vitro Evaluation for Wound Healing Applications. Pharmaceutics. 2023; 15(6):1674. https://doi.org/10.3390/pharmaceutics15061674
Chicago/Turabian StylePelin, Irina Mihaela, Mihaela Silion, Irina Popescu, Cristina Mihaela Rîmbu, Gheorghe Fundueanu, and Marieta Constantin. 2023. "Pullulan/Poly(vinyl alcohol) Hydrogels Loaded with Calendula officinalis Extract: Design and In Vitro Evaluation for Wound Healing Applications" Pharmaceutics 15, no. 6: 1674. https://doi.org/10.3390/pharmaceutics15061674
APA StylePelin, I. M., Silion, M., Popescu, I., Rîmbu, C. M., Fundueanu, G., & Constantin, M. (2023). Pullulan/Poly(vinyl alcohol) Hydrogels Loaded with Calendula officinalis Extract: Design and In Vitro Evaluation for Wound Healing Applications. Pharmaceutics, 15(6), 1674. https://doi.org/10.3390/pharmaceutics15061674