Highly Branched Betulin Based Polyanhydrides for Self-Assembled Micellar Nanoparticles Formulation
Abstract
:1. Introduction
2. Results and Discussion
2.1. Preparation and Characterization of Tricarboxylic Derivative of Poly(Ethylene glycol) PEG(COOH)3
2.2. Synthesis and Characterization of Branched Betulin-Based Polyanhydrides
2.3. Preparation and Characterization of Polymeric Micelles
3. Materials and Methods
3.1. Materials
3.2. Cell Lines and Culture Conditions
3.3. Modification of Glycerol Ethoxylate (PEG(OH)3)
3.4. Synthesis of Branched Polyanhydrides
3.5. Characterization of Polymers
3.6. Hydrolytic Degradation of Copolymers
3.7. Cytostatic Activity of Polyanhydrides
3.8. Formulation of Micelles
3.9. Maximum Polymer Concentration at Which Micelles Are Stable
3.10. Characterization of Polymers and Micelles
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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Polyanhydride | Number of DBB Molecules per 1 PEG Molecule (Feed Ratio) | Number of DBB Molecules per 1 PEG Molecule in Copolymers (1H NMR) | Molecular Weight (MALS) | DSC | ||
---|---|---|---|---|---|---|
Mn | Mw | DP | Tg (°C) | |||
DBB_PEG_COOH_5 | 39.9 | 30.8 | 13,400 | 49,800 | 3.72 | 103.4 |
DBB_PEG_COOH_10 | 18.9 | 13.3 | 15,600 | 51,600 | 3.32 | 64.0 |
DBB_PEG_COOH_20 | 8.4 | 10.8 | 16,000 | 48,800 | 3.05 | 78.6 |
DBB_PEG_COOH_30 | 4.9 | 6.9 | 12,100 | 33,300 | 2.75 | −22.2; 54.3 |
DBB_PEG_COOH_40 | 3.2 | 3.5 | 9900 | 22,800 | 2.30 | −31.2 −35.3 |
DBB_PEG_COOH_50 | 2.1 | 2.4 | 11,300 | 15,500 | 1.37 | |
DBB_PEG_COOH_60 | 1.4 | 2.0 | 10,900 | 14,700 | 1.35 | −34.2 |
DBB_PEG_COOH_70 | 0.9 | 1.0 | 10,300 | 13,600 | 1.32 | −40.7 |
DBB_PEG_COOH_80 | 0.5 | 0.6 | 12,500 | 16,400 | 1.31 | −41.8 |
DBB_PEG_COOH_90 | 0.2 | 0.04 | — | — | — | −43.2 |
Compound | Cytostatic Activity IC50 [µg/mL] | ||||
---|---|---|---|---|---|
HeLa | U-87 MG | KB | MCF-7 | A549 | |
DBB b | 8.25 ± 0.81 | 7.37 ± 0.26 | 7.17 ± 0.93 | 7.25 ± 0.79 | 7.09 ± 0.01 |
polyDBB b | 16.23 ± 0.72 | 16.07 ± 0.02 | 17.81 ± 0.03 | 13.38 ± 0.06 | 16.19 ± 0.31 |
DBB_PEG_COOH_5 | 4.99 ± 0.06 | 4.08 ± 0.03 | 4.11 ± 0.01 | 4.51 ± 0.03 | 4.12 ± 0.01 |
DBB_ PEG _COOH_10 | 4.92 ± 0.04 | 4.16 ± 0.08 | 4.48 ± 0.02 | 4.05 ± 0.22 | 4.72 ± 0.03 |
DBB_ PEG _COOH_20 | 3.88 ± 0.01 | 3.87 ± 0.01 | 3.08 ± 0.07 | 3.82 ± 0.05 | 3.84 ± 0.01 |
DBB_ PEG _COOH_30 | 6.04 ± 0.08 | 6.77 ± 0.04 | 6.93 ± 0.03 | 6.04 ± 0.11 | 6.31 ± 0.03 |
DBB_ PEG _COOH_40 | 4.97 ± 0.04 | 5.13 ± 0.02 | 5.59 ± 0.01 | 5.94 ± 0.07 | 5.09 ± 0.02 |
DBB_ PEG _COOH_50 | 6.99 ± 0.06 | 6.74 ± 0.01 | 6.29 ± 0.01 | 6.88 ± 0.09 | 6.26 ± 0.03 |
DBB_ PEG _COOH_60 | 8.04 ± 0.05 | 8.11 ± 0.07 | 8.74 ± 0.02 | 8.05 ± 0.01 | 8.75 ± 0.12 |
DBB_ PEG _COOH_70 | 8.73 ± 0.02 | 8.28 ± 0.03 | 8.14 ± 0.12 | 8.09 ± 0.01 | 8.44 ± 0.09 |
DBB_ PEG _COOH_80 | 12.08 ± 0.06 | 12.77 ± 0.11 | 12.43 ± 0.17 | 12.99 ± 0.03 | 12.41 ± 0.03 |
PEG_COOH | 36.07 ± 0.11 | 36.94 ± 0.93 | 36.12 ± 0.19 | - | 36.56 ± 0.76 |
Cytarabine c | 1.40 ± 0.08 | 1.03 ± 0.25 | 0.95 ± 0.02 | - | 1.17 ± 0.21 |
Polymer | Before Lyophilization | After Lyophilization | ||
---|---|---|---|---|
Dn ± SD [nm] | PDI | Dn ± SD [nm] | PDI | |
DBB_PEG_COOH_40 | 219.7 ± 3.3 | 0.213 | 561.8 ± 41.3 | 0.447 |
DBB_PEG_COOH_50 | 297.7 ± 2.7 | 0.229 | 295.6 ± 9.8 | 0.344 |
DBB_PEG_COOH_60 | 488.0 ± 17.0 | 0.356 | 269.4 ± 5.8 | 0.262 |
DBB_PEG_COOH_70 | 444.8 ± 9.1 | 0.272 | 290.0 ± 4.9 | 0.262 |
DBB_PEG_COOH_80 | 144.8 ± 0.9 | 0.150 | 372.2 ± 7.1 | 0.312 |
Polyanhydride | Feed Ratio (% w/w) | Feed Ratio DBB:PEG_COOH (mol/mol) | |
---|---|---|---|
DBB | PEG_COOH | ||
polyDBB_PEG_COOH_5 | 95 | 5 | 1:0.02 |
polyDBB_PEG_COOH_10 | 90 | 10 | 1:0.05 |
0polyDBB_PEG_COOH_20 | 80 | 20 | 1:0.12 |
polyDBB_PEG_COOH_30 | 70 | 30 | 1:0.20 |
polyDBB_PEG_COOH_40 | 60 | 40 | 1:0.32 |
polyDBB_PEG_COOH_50 | 50 | 50 | 1:0.48 |
polyDBB_PEG_COOH_60 | 40 | 60 | 1:0.71 |
polyDBB_PEG_COOH_70 | 30 | 70 | 1:1.11 |
polyDBB_PEG_COOH_80 | 20 | 80 | 1:1.90 |
polyDBB_PEG_COOH_90 | 10 | 90 | 1:4.29 |
polyPEG_COOH | 0 | 100 | — |
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Niewolik, D.; Bednarczyk-Cwynar, B.; Ruszkowski, P.; Dzido, G.; Jaszcz, K. Highly Branched Betulin Based Polyanhydrides for Self-Assembled Micellar Nanoparticles Formulation. Int. J. Mol. Sci. 2022, 23, 11462. https://doi.org/10.3390/ijms231911462
Niewolik D, Bednarczyk-Cwynar B, Ruszkowski P, Dzido G, Jaszcz K. Highly Branched Betulin Based Polyanhydrides for Self-Assembled Micellar Nanoparticles Formulation. International Journal of Molecular Sciences. 2022; 23(19):11462. https://doi.org/10.3390/ijms231911462
Chicago/Turabian StyleNiewolik, Daria, Barbara Bednarczyk-Cwynar, Piotr Ruszkowski, Grzegorz Dzido, and Katarzyna Jaszcz. 2022. "Highly Branched Betulin Based Polyanhydrides for Self-Assembled Micellar Nanoparticles Formulation" International Journal of Molecular Sciences 23, no. 19: 11462. https://doi.org/10.3390/ijms231911462
APA StyleNiewolik, D., Bednarczyk-Cwynar, B., Ruszkowski, P., Dzido, G., & Jaszcz, K. (2022). Highly Branched Betulin Based Polyanhydrides for Self-Assembled Micellar Nanoparticles Formulation. International Journal of Molecular Sciences, 23(19), 11462. https://doi.org/10.3390/ijms231911462