Article Title

Size-tunable nanoparticles composed of dextran-b-poly(D,L-lactide) for drug delivery applications

Authors

Mohit S. Verma, Department of Chemical Engineering, University of Waterloo, Waterloo N2L 3G1, Canada
Shengyan Liu, Department of Chemical Engineering, University of Waterloo, Waterloo N2L 3G1, Canada
Yih Y. Chen, Department of Chemical Engineering, University of Waterloo, Waterloo N2L 3G1, Canada
Ameena Meerasa, Department of Chemical Engineering, University of Waterloo, Waterloo N2L 3G1, Canada
Frank X. Gu, Department of Chemical Engineering, University of Waterloo, Waterloo N2L 3G1, Canada Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo N2L 3G1, Canada

Keywords

Dextran, nanoparticles, biodistribution, pharmacokinetics, controlled drug delivery, in vivo

Abstract

Nanoparticles (NPs) formulated using self-assembly of block copolymers have attracted significant attention as nano-scaled drug delivery vehicles. Here we report the development of a biodegradable NP using self-assembly of a linear amphiphilic block copolymer, Dex-b-PLA, composed of poly(D,L-lactide), and dextran. The size of the NPs can be precisely tuned between 15 and 70 nm by altering the molecular weight (MW) of the two polymer chains. Using doxorubicin as a model drug, we demonstrated that the NPs can carry up to 21% (w/w) of the drug payload. The release profile of doxorubicin from NPs showed sustained release for over 6 days. Using a rat model, we explored the pharmacokinetics profiles of Dex-b-PLA NPs, and showed proof-of-concept that long circulation lifetime of the NPs can be achieved by tuning the MW of Dex-b-PLA block copolymer. While the terminal half-life of Dex-b-PLA NPs (29.8 h) was similar to that observed in poly(ethylene glycol)-coated (PEG-coated) NPs (27.0 h), 90% of the injected Dex-b-PLA NPs were retained in the blood circulation for 38.3 h after injection, almost eight times longer than the PEG-coated NPs. The area under curve (AUC) of Dex-b-PLA NPs was almost four times higher than PEG-based NPs. The biodistribution study showed lower accumulation of Dex-b-PLA NPs in the spleen with 19.5% initial dose per gram tissue (IDGT) after 24 h compared to PEG-coated poly(lactide-co-glycolide) (PLGA) NPs (29.8% IDGT). These studies show that Dex-b-PLA block copolymer is a promising new biomaterial for making controlled nanoparticles as drug delivery vehicles.

Graphical Abstract

DOI

https://doi.org/10.1007/s12274-011-0184-z

Publisher

Tsinghua University Press

Recommended Citation

Mohit S. Verma,Shengyan Liu,Yih Y. Chen,Ameena Meerasa,Frank X. Gu, Size-tunable nanoparticles composed of dextran-b-poly(D,L-lactide) for drug delivery applications. NanoRes.2012, 5(1): 49–61