Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. siRNA Synthesis
2.3. Solubilization of Nanotubes
2.4. UV-Vis to Estimate DSPE-PEG-NH2 Loading
2.5. MTX Coupling
2.6. PEI Coupling to Carboxyl-SWCNTs
2.7. Cy5.5 Conjugation to SWCNTs
2.8. siRNA Attachment
2.9. Nanotube Conjugates Incubation with Human Blood
2.10. In Vivo Study in Mice
2.11. Flow Cytometry Staining and Analysis in Human Blood
2.12. SEM Studies
2.13. In Vitro Studies
3. Results
3.1. PEGylating of Carbon Nanotubes
3.2. MTX Loading of Carbon Nanotubes
3.3. siRNA Attachment
3.4. Study in Mice
3.5. SWCNT Study in Human Whole Blood
3.6. Bone Marrow Study
3.7. In Vitro siRNA Stability and SEM
4. Discussion
5. 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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Name | Nanotube | PEG/EE% | PEI | RNA Attachment/Efficiency (%) | Drug/CE% |
---|---|---|---|---|---|
C1 | HiPco-SWCNT | mPEG-DSPE, DSPE-PEG-NH2/52% | - | siRNA/97% | MTX/79% |
C2 | HiPco-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | siRNA/91% | - |
C3 | HiPco-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | sc siRNA/93% | MTX/78% |
C4 | HiPco-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | sc siRNA/90% | - |
C5 | HiPco-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | - | MTX/77% |
C6 | HiPco-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | - | - |
C7 | Carboxyl-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | PEI | siRNA/91% | MTX/78% |
C8 | Carboxyl-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | siRNA/98% | - |
C9 | Carboxyl-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | PEI | sc siRNA/90% | MTX/71% |
C10 | Carboxyl-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | sc siRNA/87% | - |
C11 | Carboxyl-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | - | MTX/83% |
C12 | Carboxyl-SWCNT | mPEG-DSPE, DSPE-PEG-NH2 | - | - | - |
Name | Sequence | Purity (%) | Yield (%) |
---|---|---|---|
NOCH1_s | 5′-r(ACUAUGCUCGUUCAACUUCCCmUmU)-3ʹ | 90 | 10 |
NOCH1_as | 5′-r(GGGAAGUUGAACGAGCAUAGUmUmU)-3′ | 94 | 4 |
sc_s | 5′-r(AUGAUCCACGUUCUUUCACCCmUmU)-3′ | 94 | 5 |
sc_as | 5′-r(GGGUGAAAGAACGUGGAUCAUmUmU)-3′ | 99 | 5 |
Applied Conjugate | C1 (Amount of siRNA Released (µg)/Release%) | C3 (Amount of siRNA Released (µg)/Release%) | Control Naked siRNA (µg/Release%) |
---|---|---|---|
Time Points | |||
0 min | 1.36 (91%) | 1.28 (85%) | 0.96 (64%) |
30 min | 1.2 (80%) | 0.8 (53%) | 0.8 (53%) |
1 h | 0.72 (48%) | 0.64 (43%) | nd |
2 h | 0.64 (43%) | 0.4 (27%) | nd |
4 h | 0.24 (16%) | 0.16 (11%) | nd |
8 h | 0.16 (11%) | nd | nd |
Product | Average Diameter Size/nm | PDI |
---|---|---|
Solubilized HiPco-SWCNT | 343.5 ± 42.58 | 0.015 |
C1 | 518.8 ± 114.64 | 0.049 |
C3 | 407.67 ± 120.21 | 0.087 |
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Kofoed Andersen, C.; Khatri, S.; Hansen, J.; Slott, S.; Pavan Parvathaneni, R.; Mendes, A.C.; Chronakis, I.S.; Hung, S.-C.; Rajasekaran, N.; Ma, Z.; et al. Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis. Pharmaceutics 2021, 13, 453. https://doi.org/10.3390/pharmaceutics13040453
Kofoed Andersen C, Khatri S, Hansen J, Slott S, Pavan Parvathaneni R, Mendes AC, Chronakis IS, Hung S-C, Rajasekaran N, Ma Z, et al. Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis. Pharmaceutics. 2021; 13(4):453. https://doi.org/10.3390/pharmaceutics13040453
Chicago/Turabian StyleKofoed Andersen, Camilla, Sangita Khatri, Jonas Hansen, Sofie Slott, Rohith Pavan Parvathaneni, Ana C. Mendes, Ioannis S. Chronakis, Shu-Chen Hung, Narendiran Rajasekaran, Zhuoran Ma, and et al. 2021. "Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis" Pharmaceutics 13, no. 4: 453. https://doi.org/10.3390/pharmaceutics13040453
APA StyleKofoed Andersen, C., Khatri, S., Hansen, J., Slott, S., Pavan Parvathaneni, R., Mendes, A. C., Chronakis, I. S., Hung, S.-C., Rajasekaran, N., Ma, Z., Zhu, S., Dai, H., Mellins, E. D., & Astakhova, K. (2021). Carbon Nanotubes—Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis. Pharmaceutics, 13(4), 453. https://doi.org/10.3390/pharmaceutics13040453