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Issue 3, 2012
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Microfluidic approach for highly efficient synthesis of heparin-based bioconjugates for drug delivery

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Abstract

This paper demonstrates the highly efficient synthesis of amphiphilic heparin-folic acid-retinoic acid (HFR) bioconjugates with a high drug coupling ratio by a microfluidic approach. The microfluidic synthesis enabled the conjugation of 17 molecules of retinoic acid to each heparin chain with 21 possible groups for attachment after reacting for several minutes. In contrast, about 11 molecules of the drug were covalently conjugated to one heparin chain after 4 days in the bulk reaction. The microfluidic based-HFR bioconjugates readily self-assembled in aqueous media to form uniform nanoparticles, while the product from the bulk reaction formed non-uniform nanoparticles with broad size distribution. The HFR nanoparticles with high drug content effectively delivered the drug to folate receptor-positive cancer cells with superior cellular uptake and selective cytotoxicity in vitro compared to HFR nanoparticles synthesized in bulk reaction. With the ability to achieve high drug content in heparin carrier within a short reaction time, the microfluidic technique offers new alternatives for the efficient synthesis of polymer-based conjugates for drug delivery.

Graphical abstract: Microfluidic approach for highly efficient synthesis of heparin-based bioconjugates for drug delivery

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Publication details

The article was received on 17 Aug 2011, accepted on 31 Oct 2011 and first published on 02 Dec 2011


Article type: Paper
DOI: 10.1039/C1LC20769E
Lab Chip, 2012,12, 589-594

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    Microfluidic approach for highly efficient synthesis of heparin-based bioconjugates for drug delivery

    T. H. Tran, C. T. Nguyen, D. Kim, Y. Lee and K. M. Huh, Lab Chip, 2012, 12, 589
    DOI: 10.1039/C1LC20769E

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