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Dendrimer Versus Linear Conjugate: Influence of Polymeric Architecture on the Delivery and Anticancer Effect of Paclitaxel
Abstract
The relative difference in polymeric architectures of dendrimer and linear bis(poly(ethylene glycol)) (PEG) polymer in conjugation with paclitaxel has been described. Paclitaxel, a poorly soluble anticancer drug, was covalently conjugated with PAMAM G4 hydroxyl-terminated dendrimer and bis(PEG) polymer for the potential enhancement of drug solubility and cytotoxicity. Both conjugates were characterized by 1NMR, HPLC, and MALDI/TOF. In addition, molecular conformations of dendrimer, bis(PEG), paclitaxel, and its polymeric conjugates were studied by molecular modeling. Hydrolysis of the ester bond in the conjugate was analyzed by HPLC using esterase hydrolyzing enzyme. In vitro cytotoxicity of dendrimer, bis(PEG), paclitaxel, and polymeric conjugates containing paclitaxel was evaluated using A2780 human ovarian carcinoma cells. Cytotoxicity increased by 10-fold with PAMAM dendrimer-succinic acid-paclitaxel conjugate when compared with free nonconjugated drug. Data obtained indicate that the nanosized dendritic polymer conjugates can be used with good success as anticancer drug carriers.
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Cited by
Polymers for Drug Delivery Systems
Liechty, W. B., Kryscio, D. R., Slaughter, B. V., & Peppas, N. A. (2010) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-073009-100847 · Cited by 1,608
Therapeutic Protein–Polymer Conjugates: Advancing Beyond PEGylation
Pelegri-O’Day, E. M., Lin, E.-W., & Maynard, H. D. (2014) · Journal of the American Chemical Society · doi:10.1021/ja504390x · Cited by 622
Polymeric Conjugates for Drug Delivery
Larson, N., & Ghandehari, H. (2012) · Chemistry of Materials · doi:10.1021/cm2031569 · Cited by 580
Lee, E. S., Oh, K. T., Kim, D., Youn, Y. S., & Bae, Y. H. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.08.006 · Cited by 446
Nanocarrier-based systems for targeted and site specific therapeutic delivery
Majumder, J., Taratula, O., & Minko, T. (2019) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.07.010 · Cited by 394
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Metadata
- Authors
- Khandare, J. J., Jayant, S., Singh, A., Chandna, P., Wang, Y., Vorsa, N., & Minko, T.
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-10-20
- Volume
- 17
- Issue
- 6
- Pages
- 1464-1472
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W2062469291
- Cited by
- 226
- References
- 0
- FWCI
- 15.25
- Type
- journal article
- Language
- en
- Open access
- closed
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- Khandare, J. J., Jayant, S., Singh, A., Chandna, P., Wang, Y., Vorsa, N., & Minko, T. (2006). Dendrimer Versus Linear Conjugate: Influence of Polymeric Architecture on the Delivery and Anticancer Effect of Paclitaxel. Bioconjugate Chemistry. https://doi.org/10.1021/bc060240p
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