Poly(2-Deoxy-2-Methacrylamido-D-Glucose)-Based Complex Conjugates of Colistin, Deferoxamine and Vitamin B12: Synthesis and Biological Evaluation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Synthesis of Conjugates
2.2.2. Characterization of Precursors and Conjugates
2.2.3. Antibacterial Activity Study
2.2.4. Cytotoxicity Study
2.2.5. Caco-2 Cell Permeability Assay
2.2.6. Stability of Conjugates and Colistin Release Study
2.2.7. Statistical Analysis
3. Results and Discussion
3.1. Synthesis and Characterization of PMAG-Based Conjugates
3.2. In Vitro Biological Properties of Conjugates
3.2.1. Antibacterial Activity
3.2.2. Cytotoxicity
3.2.3. Caco-2 Cell Permeability
3.3. Stability of Conjugates in Gastrointestinal Simulated Media
3.4. Colistin Release from Conjugates
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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Conjugate a | Content of CHO-Groups in PMAG (mol%) | Initial Amounts of Substances (m0) b (μg/mg PMAG) | Content of Conjugated Substances (mC) (μg/mg PMAG) | Conjugation Efficacy c (%) | |||
---|---|---|---|---|---|---|---|
CT | DFOA | CT | DFOA | CT | DFOA d | ||
PMAG(10)-CT | 10 | 870 | - | 454 ± 39 | - | 52 ± 4 | - |
PMAG(20)-CT | 20 | 1740 | - | 710 ± 81 | - | 41 ± 5 | - |
PMAG(10)-DFOA | 10 | - | 2680 | - | 218 ± 22 | - | 41 ± 4 |
PMAG(20)-DFOA | 20 | - | 5360 | - | 610 ± 54 | - | 57 ± 5 |
PMAG(10)-(DFOA,CT) | 10 | 870 | 2680 | 415 ± 36 | 294 ± 31 | 48 ± 4 | 55 ± 6 |
PMAG(20)-(DFOA,CT) | 20 | 1740 | 5360 | 791 ± 97 | 563 ± 47 | 45 ± 6 | 53 ± 4 |
Conjugate a | Initial Amount of Suc-B12 (B12) b (μg/mg Conjugate) | Amount of Conjugated Suc-B12 (B12) (μg/mg Conjugate) | Conjugation Efficacy (%) |
---|---|---|---|
PMAG(10)-(DFOA,CT-B12) (aldimine bonds) | 363 (339) | 356 ± 7 (332 ± 7) | 98 ± 2 |
PMAG(10)-(DFOA,CT-B12) (reduced aldimine bonds) | 363 (339) | 352 ± 11 (329 ± 10) | 97 ± 3 |
Conjugate | Content of Components in Conjugate (μg/mg Conjugate) | ||
---|---|---|---|
CT | DFOA | B12 | |
PMAG(10)-CT | 312 | – | – |
PMAG(20)-CT | 415 | – | – |
PMAG(10)-DFOA | – | 179 | – |
PMAG(20)-DFOA | – | 379 | – |
PMAG(10)-(DFOA,CT) | 243 | 172 | – |
PMAG(20)-(DFOA,CT) | 336 | 239 | – |
PMAG(10)-(DFOA,CT-B12) | 180 | 127 | 244 |
Conjugate | Conditions | Time (h) | Release of CT (%) |
---|---|---|---|
PMAG(10)-(DFOA, CT) * | FaSSGF (pH 1.6) | 2 | 20 ± 4 |
FaSSIF (pH 6.5) | 2 | 6 ± 2 | |
0.1 M HCl (pH 1.0) | 2 | 26 ± 6 | |
PB (pH 6.8) | 2 | 9 ± 2 | |
PMAG(10)-(DFOA, CT) ** | FaSSGF (pH 1.6) | 2 | 6 ± 2 |
FaSSIF (pH 6.5) | 2 | ~2 | |
0.1 M HCl (pH 1.0) | 2 | 12 ± 2 | |
PB (pH 6.8) | 2 | ~2 |
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Stepanova, M.; Levit, M.; Egorova, T.; Nashchekina, Y.; Sall, T.; Demyanova, E.; Guryanov, I.; Korzhikova-Vlakh, E. Poly(2-Deoxy-2-Methacrylamido-D-Glucose)-Based Complex Conjugates of Colistin, Deferoxamine and Vitamin B12: Synthesis and Biological Evaluation. Pharmaceutics 2024, 16, 1080. https://doi.org/10.3390/pharmaceutics16081080
Stepanova M, Levit M, Egorova T, Nashchekina Y, Sall T, Demyanova E, Guryanov I, Korzhikova-Vlakh E. Poly(2-Deoxy-2-Methacrylamido-D-Glucose)-Based Complex Conjugates of Colistin, Deferoxamine and Vitamin B12: Synthesis and Biological Evaluation. Pharmaceutics. 2024; 16(8):1080. https://doi.org/10.3390/pharmaceutics16081080
Chicago/Turabian StyleStepanova, Mariia, Mariia Levit, Tatiana Egorova, Yulia Nashchekina, Tatiana Sall, Elena Demyanova, Ivan Guryanov, and Evgenia Korzhikova-Vlakh. 2024. "Poly(2-Deoxy-2-Methacrylamido-D-Glucose)-Based Complex Conjugates of Colistin, Deferoxamine and Vitamin B12: Synthesis and Biological Evaluation" Pharmaceutics 16, no. 8: 1080. https://doi.org/10.3390/pharmaceutics16081080