Journal
JOURNAL OF MATERIALS CHEMISTRY
Volume 21, Issue 39, Pages 15288-15297Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c1jm11944c
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Funding
- Chungnam National University
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To achieve a targeted drug delivery system for chemotherapy, we synthesized a ligand-mediated nanoparticulate drug carrier composed of folate-conjugated heparin-based copolymers. The use of a heparin-based drug delivery system is of special interest due to the attractive anticancer properties of heparin. Heparin-poly(beta-benzyl-L-aspartate) (HP) and folate-poly(ethylene glycol)-conjugated HP (FPHP) amphiphilic copolymers were synthesized for delivery of doxorubicin (DOX). DOX was effectively incorporated into HP and FPHP nanoparticles at a high loading content and efficiency by a simple dialysis method. The DOX-loaded HP and FPHP nanoparticles had average diameters of 86210 nm, depending on the drug loading content and the compositions of copolymers. Both DOX-loaded HP and FPHP nanoparticles had a sustained drug release pattern, and DOX-release from nanoparticles at pH 5.0 was much faster than that at pH 7.4. This pH-dependent DOX release property may ensure intracellular drug release due to decreases in pH values inside the endosomes and lysosomes of tumor cells. Furthermore, the DOX-loaded FPHP nanoparticles exhibited a greater extent of intracellular uptake against folate-receptor positive KB cells than DOX-loaded HP nanoparticles, indicating that the FPHP nanoparticles may serve as an effective active targeting carrier. The DOX-loaded FPHP nanoparticles also showed more potent cytotoxic effect on KB cells than on folate-receptor negative A549 cells. These results suggested that the FPHP nanoparticle is a promising candidate for targeted delivery of anticancer drugs to folate-receptor positive cells.
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