Polyester Dendritic Systems for Drug Delivery Applications: In Vitro and In Vivo Evaluation
Abstract
High molecular weight polymers (> 20 000 Da) have been widely used as soluble drug carriers to improve drug targeting and therapeutic efficacy. Dendritic polymers are exceptional candidates for the preparation of near monodisperse drug carriers due to their well-defined structure, multivalency, and flexibility for tailored functionalization. We evaluated various dendritic architectures composed of a polyester dendritic scaffold based on the monomer unit 2,2-bis(hydroxymethyl)propanoic acid for their suitability as drug carriers both in vitro and in vivo. These systems are both water soluble and nontoxic. In addition, the potent anticancer drug, doxorubicin, was covalently bound via a hydrazone linkage to a high molecular weight 3-arm poly(ethylene oxide)-dendrimer hybrid. Drug release was a function of pH, and the release rate was more rapid at pH < 6. The cytotoxicity of the DOX-polymer conjugate measured on multiple cancer lines in vitro was reduced but not eliminated, indicating that some active doxorubicin was released from the drug polymer conjugate under physiological conditions. Furthermore, biodistribution experiments show little accumulation of the DOX-polymer conjugate in vital organs, and the serum half-life of doxorubicin attached to an appropriate high molecular weight polymer has been significantly increased when compared to the free drug. Thus, this new macromolecular system exhibits promising characteristics for the development of new polymeric drug carriers.
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Novel water-soluble and biocompatible dendritic systems have been developed using 2,2-bis(hydroxymethyl)-propanoic acid as a drug carrier for doxorubicin.
“Novel water-soluble and biocompatible dendritic systems have been developed using 2,2-bis(hydroxymethyl)-propanoic acid as a drug carrier for doxorubicin.243”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [243]
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- Authors
- Padilla De Jesús, O. L., Ihre, H. R., Gagne, L., Fréchet, J. M. J., & Szoka, F. C.
- Affiliations
- Department of Chemistry, University of California, Berkeley, California 94720-1460 and School of Pharmacy, University of California, San Francisco, California 94143-0446
- University of California, San Francisco (US)
- Venue
- Bioconjugate Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2002-04-24
- Volume
- 13
- Issue
- 3
- Pages
- 453-461
- ISSN
- 1043-1802 (ISSN-L)
- 1520-4812
- OpenAlex
- W2061840262
- Cited by
- 507
- References
- 43
- Citations by year
- 2025: 5 · 2024: 6 · 2023: 9 · 2022: 12 · 2021: 14 · 2020: 13 · 2019: 18 · 2018: 14 · 2017: 12 · 2016: 15 · 2015: 31 · 2014: 44 · 2013: 33 · 2012: 34
- FWCI
- 24.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioconjugate Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM065361, GM65361)
- Topics
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- polyester dendrimers, dendritic polymers, drug delivery, doxorubicin, hydrazone linkage, pH-responsive drug release, serum half-life, tissue distribution, cytotoxicity, anticancer drug carriers, high molecular weight polymers
- MeSH terms
- Animals, Antibiotics, Antineoplastic, Cell Division, Cells, Cultured, Doxorubicin, Drug Carriers, Drug Screening Assays, Antitumor, Female, Hydrogen-Ion Concentration, Metabolic Clearance Rate, Microscopy, Fluorescence, Oxidation-Reduction, Polyesters, Polymers, Drug Design, Drug Delivery Systems, Microscopy, Confocal, Mice
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