Dual fluorescent HPMA copolymers for passive tumor targeting with pH-sensitive drug release II: impact of release rate on biodistribution
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23697767
DOI
10.1016/j.jconrel.2013.05.008
PII: S0168-3659(13)00255-1
Knihovny.cz E-resources
- Keywords
- HPMA copolymers, Multispectral optical imaging, Passive tumor targeting, Tumor accumulation, Xenograft tumor model, pH-responsive drug release,
- MeSH
- Acrylamides analysis MeSH
- Fluorescent Dyes administration & dosage pharmacokinetics MeSH
- Indoles administration & dosage pharmacokinetics MeSH
- Carbocyanines administration & dosage pharmacokinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Delayed-Action Preparations analysis MeSH
- Humans MeSH
- Models, Molecular MeSH
- Mice, Nude MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Colonic Neoplasms drug therapy MeSH
- Tissue Distribution MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acrylamides MeSH
- DY-676 MeSH Browser
- Fluorescent Dyes MeSH
- Indoles MeSH
- Carbocyanines MeSH
- Delayed-Action Preparations MeSH
- N-(2-hydroxypropyl)methacrylamide MeSH Browser
In recent years, polymer drug carriers based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers with pH-triggered drug release have shown enhanced uptake in solid tumors and excellent antitumor activity. Here, the impact of the structure of the acid-labile spacer between the drug and the polymer carrier on the biodistribution of both the drug and the carrier was studied using in vivo noninvasive multispectral optical imaging of dual fluorescently labeled HPMA copolymers. Five different spacers containing a pH-sensitive hydrazone bond were synthesized and used to combine a fluorescent model drug with a polymer backbone, conjugated with another non-releasable fluorescent dye. Two copolymers differing in polymer chain structure (linear and star-like) and molecular weight (30 and 200kDa) were used to distinguish between carriers with molecular weights above and below the limit for renal filtration. The rate of model drug release from the conjugates was determined in vitro. The biodistributions of the six most promising conjugates were investigated in vivo in athymic nude mice inoculated with human colon carcinoma xenograft. The structure of the spacer in the vicinity of the hydrazone bond significantly influenced the release rate of the model drug. The slow release rate of a pyridyl group bearing spacer resulted in a greater amount of the model drug being transported to the tumor, which was independent of the carrier structure. The results of this study emphasize the importance of careful selection of the structure and appropriate spacer when designing polymer conjugates intended for passive tumor targeting.
References provided by Crossref.org
HPMA Copolymer-Based Nanomedicines in Controlled Drug Delivery
Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery
