Highly Efficient Modular Construction of Functional Drug Delivery Platform Based on Amphiphilic Biodegradable Polymers via Click Chemistry
Abstract
:1. Introduction
2. Results and Discussion
2.1. Syntheses of mPEG-b-P(AVL-co-LA) (PPAL) and mPEG-b-P(AVL-co-CL) (PPAC) Copolymers with Pendant Alkynyl Groups
2.2. Functionalization of PPAL and PPAC Copolymers by Click Chemistry
2.3. Self-Assembly of Functional Polymeric Nanoparticles
2.4. Degradation Study
2.5. Cytotoxicity Assay
3. Materials and Methods
3.1. Materials
3.2. Instruments
3.3. Synthesis of α-Propargyl-δ-valerolactone (AVL)
3.4. General Procedure for Synthesis of mPEG-b-P(AVL-co-LA) (PPAL) and mPEG-b-P(AVL-co-CL) (PPAC) Copolymers
3.5. General Procedure for Modification of mPEG-b-P(AVL-co-LA) (PPAL) and mPEG-b-P(AVL-co-CL) (PPAC) Copolymers by CuAAC Click Chemistry
3.6. Preparation of Polymeric Nanoparticles
3.7. Characterization of Polymeric Nanoparticles
3.8. Determination of Critical Micelle Concentration (CMC)
3.9. In Vitro Degradation Study
3.10. Cell Culture
3.11. Cytotoxicity Assay
4. 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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Copolymer | [LA] or [CL]/[AVL] Molar Ratio in the Feed | Mn,NMR(a) (g moL−1) | Mn,GPC (b) (g moL−1) | PDI (c) | Number of Alkynyl (d) |
---|---|---|---|---|---|
mPEG2K-b-P(AVL-co-LA)2K (AVL:LA = 1:1) (PPAL1) | 1/1.9 | 4100 | 3600 | 1.33 | 7 |
mPEG2K-b-P(AVL-co-LA)2K (AVL:LA = 1:3) (PPAL2) | 3/1.9 | 3900 | 4200 | 1.31 | 4 |
mPEG4K-b-P(AVL-co-LA)4K (AVL:LA = 1:1) (PPAL3) | 1/1.9 | 7800 | 6900 | 1.25 | 14 |
mPEG4K-b-P(AVL-co-LA)4K (AVL:LA = 1:3) (PPAL4) | 3/1.9 | 7600 | 8000 | 1.30 | 7 |
mPEG2K-b-P(AVL-co-CL)2K (AVL:CL = 1:1) (PPAC1) | 1/1.9 | 3900 | 4200 | 1.27 | 7 |
mPEG2K-b-P(AVL-co-CL)2K (AVL:CL = 1:3) (PPAC2) | 3/1.9 | 3900 | 4300 | 1.25 | 4 |
mPEG4K-b-P(AVL-co-CL)4K (AVL:CL = 1:1) (PPAC3) | 1/1.9 | 7500 | 7000 | 1.23 | 12 |
mPEG4K-b-P(AVL-co-CL)4K (AVL:CL = 1:3) (PPAC4) | 3/1.9 | 7800 | 8100 | 1.31 | 7 |
mPEG2K-b-P(AVL-co-LA)2K (AVL:LA = 1:1) (PPAL1) | |||||
---|---|---|---|---|---|
Azido Molecule | Grafting Efficiency (a) (%) | Yield (%) | Mn,NMR (b) (g mol−1) | Mn,GPC(c) (g mol−1) | PDI (d) |
1 | 98.6 | 65.5 | 4100 | 5800 | 1.25 |
2 | 96.7 | 69.5 | 5100 | 5600 | 1.28 |
3 | 100.0 | 82.5 | 5300 | 5300 | 1.28 |
4 | 93.9 | 75.0 | 5100 | 4400 | 1.32 |
5 | 100.0 | 74.0 | 5100 | 5900 | 1.24 |
6 | 98.3 | 85.6 | 5100 | 4800 | 1.14 |
7 | 86.3 | 70.0 | 5100 | 4900 | 1.20 |
8 | 83.6 | 91.5 | 4600 | 5100 | 1.22 |
9 | 98.4 | 70.2 | 4700 | 4500 | 1.22 |
Functional Copolymer | Particle Size (nm) | PDI | CMC (mg mL−1) |
---|---|---|---|
PPAL1 1 | 159.65 ± 5.6 | 0.153 ± 0.02 | 0.059 |
PPAL1 2 | 18.83 ± 1.2 | 0.312 ± 0.04 | 0.037 |
PPAL1 3 | 27.27 ± 3.2 | 0.140 ± 0.02 | 0.007 |
PPAL1 4 | 18.14 ± 3.0 | 0.259 ± 0.01 | 0.010 |
PPAL1 5 | 16.75 ± 0.7 | 0.301 ± 0.04 | 0.023 |
PPAL1 6 | 35.13 ± 2.9 | 0.248 ± 0.05 | 0.071 |
PPAL1 7 | 139.7 ± 5.4 | 0.141 ± 0.03 | 0.075 |
PPAL1 8 | 16.69 ± 3.3 | 0.218 ± 0.01 | 0.058 |
PPAL1 9 | 22.09 ± 4.2 | 0.261 ± 0.02 | 0.034 |
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Zhao, G.; Ge, T.; Yan, Y.; Shuai, Q.; Su, W.-K. Highly Efficient Modular Construction of Functional Drug Delivery Platform Based on Amphiphilic Biodegradable Polymers via Click Chemistry. Int. J. Mol. Sci. 2021, 22, 10407. https://doi.org/10.3390/ijms221910407
Zhao G, Ge T, Yan Y, Shuai Q, Su W-K. Highly Efficient Modular Construction of Functional Drug Delivery Platform Based on Amphiphilic Biodegradable Polymers via Click Chemistry. International Journal of Molecular Sciences. 2021; 22(19):10407. https://doi.org/10.3390/ijms221910407
Chicago/Turabian StyleZhao, Guangkuo, Tongtong Ge, Yunfeng Yan, Qi Shuai, and Wei-Ke Su. 2021. "Highly Efficient Modular Construction of Functional Drug Delivery Platform Based on Amphiphilic Biodegradable Polymers via Click Chemistry" International Journal of Molecular Sciences 22, no. 19: 10407. https://doi.org/10.3390/ijms221910407