Research Article

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2012, 5(1): 49–61

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

Size-Tunable Nanoparticles Composed of Dextran-b-poly(D,L-lactide) for Drug Delivery Applications

Mohit S. Verma1,§, Shengyan Liu1,§, Yih Y. Chen1, Ameena Meerasa1, and Frank X. Gu1,2 ()

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1 Department of Chemical Engineering, University of Waterloo, Waterloo N2L 3G1, Canada
2 Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo N2L 3G1, Canada
§ These authors contributed equally to this work

Keywords: Dextran, nanoparticles, biodistribution, pharmacokinetics, controlled drug delivery, in vivo
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  • Abstract
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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.
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Size-Tunable Nanoparticles Composed of Dextran-b-poly(D,L-lactide) for Drug Delivery Applications. Nano Res. 2012, 5(1): 49–61 https://doi.org/10.1007/s12274-011-0184-z

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