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Bioadhesive chitosan-coated cyclodextrin-based superamolecular nanomicelles to enhance the oral bioavailability of doxorubicin

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Abstract

In order to improve the oral bioavailability of doxorubicin (Dox), a novel bioadhesive nanomicelle based on host–guest interaction was developed in this study. Hyaluronic acid-linked β-cyclodextrin (HA–CD) was synthesized. The primary nanomicelles were formed through the self-assemble of HA–CD and retinoic acid (RA) which was included as the hydrophobic core to anchor CD cavity by host–guest interaction. Chitosan (CS) was then coated on the surface of primary nanomicelles by ionic interaction with the negatively charged HA. The critical micellar concentration of HA–CD–RA was as low as 22.5 μg/mL. Dox was successfully encapsulated into the hydrophobic core of CS-coated HA–CD–RA nanomicelles (CS/HA–CD–RA–Dox), with encapsulation efficiency as high as 89.2 %. The CS/HA–CD–RA–Dox particle size was 234 nm and was stable over 30 days. In vitro Dox release showed that CS/HA–CD–RA nanomicelles were more sustained than HA–CD–RA nanomicelles, and Dox encapsulated into CS-coated nanomicelles was stable at low pH. The in situ single pass intestinal perfusion revealed that encapsulation of Dox into CS/HA–CD–RA nanomicelles could significantly improve the intestinal permeability of Dox. The mucoadhesion results indicated that the retention percentage of CS/HA–CD–RA nanomicelles was significantly higher than that of HA–CD–RA nanomicelles in gastrointestinal tract. In vivo pharmacokinetic study revealed that AUC(0−∞) of CS/HA–CD–RA nanomicelles was about fourfold higher than that of Dox solution. The present study suggested that CS/HA–CD–RA nanomicelles as biodegradable, biocompatible, and bioadhesive nanostructure can be a promising nanocarrier in improving the bioavailability of anticancer drugs to facilitate the oral chemotherapy.

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Acknowledgments

This work was financially supported from the National Nature Science Foundation of China (No. 81173008, 81273450), Program for New Century Excellent Talents in University (No. NCET-12-1015) and the National Basic Research Program of China (973 Program) (No. 2015CB932100).

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Authors and Affiliations

  1. Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang, Mailbox 32#, Shenyang, 110016, China

    Yuhai Liu, Xiaopeng Han, Xiaohong Liu, Wanjun Liu, Chunnuan Wu, Lin Li, Yuqian Du, He Lian, Yongjun Wang, Zhonggui He & Jin Sun

  2. School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Yinglei Zhai

  3. State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, China

    Jin Sun

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  1. Yuhai Liu
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  2. Yinglei Zhai
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  3. Xiaopeng Han
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  4. Xiaohong Liu
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  5. Wanjun Liu
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  7. Lin Li
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  9. He Lian
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  10. Yongjun Wang
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  12. Jin Sun
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Correspondence to Jin Sun.

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Liu, Y., Zhai, Y., Han, X. et al. Bioadhesive chitosan-coated cyclodextrin-based superamolecular nanomicelles to enhance the oral bioavailability of doxorubicin. J Nanopart Res 16, 2587 (2014). https://doi.org/10.1007/s11051-014-2587-8

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