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Chitosan-Based Polyelectrolyte Complexes as Potential Nanoparticulate Carriers: Physicochemical and Biological Characterization

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ABSTRACT

Purpose

To investigate the effect of polyelectrolytes on the formation and physicochemical properties of chitosan nanoparticles (CS-NPs) used for the delivery of an anticancer drug, doxorubicin (DOX).

Method

Three DOX-loaded CS-NPs were formulated with tripolyphosphate (CS-TP/DOX NPs), dextran sulfate (CS-DS/DOX NPs), and hyaluronic acid (CS-HA/DOX NPs) by using ionotropic gelation or complex coacervation.

Results

CS-TP/DOX NPs were the smallest, with an average size of ~100 nm and a narrow size distribution, while CS-DS/DOX and CS-HA/DOX NPs were ~200 nm in size. Transmission electron microscopy clearly showed a spherical shape for all the NPs. The strong binding affinity of DOX for the multiple sulfate groups in DS resulted in a sustained release profile from CS-DS/DOX NPs at pH 7.4, while CS-HA/DOX NPs exhibited faster DOX release. This trend was also present under acidic conditions, where release of DOX was significantly augmented because of polymer protonation. Compared to CS-TP/DOX or CS-DS/DOX NPs, CS-HA/DOX NPs showed superior cellular uptake and cytotoxicity in MCF-7 and A-549 cells, because of their ability to undergo CD44-mediated endocytosis. Pharmacokinetic studies clearly showed that all CS-NPs tested significantly improved DOX plasma circulation time and decreased its elimination rate constant. Consistent with the in vitro release data, CS-DS/DOX NPs exhibited a relatively better DOX plasma profile and enhanced blood circulation, compared to CS-HA/DOX or CS-TP/DOX NPs. Overall, these results demonstrated how NP design can influence their function.

Conclusions

Taken together, CS-based polyelectrolyte complexes could provide a versatile delivery system with enormous potential in the pharmaceutical and biomedical sectors.

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ACKNOWLEDGMENTS AND DISCLOSURES

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (No. 2012R1A2A2A02044997 and No. 2012R1A1A1039059).

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Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan, 712-749, South Korea

    Thiruganesh Ramasamy, Tuan Hiep Tran, Hyuk Jun Cho, Jeong Hwan Kim, Yong Il Kim, Chul Soon Yong & Jong Oh Kim

  2. College of Pharmacy, Hanyang University, 55, Hanyangdaehak-ro, Ansan, 426-791, South Korea

    Han-Gon Choi

  3. Ernest Mario School of Pharmacy, Rutgers University, New Brunswick, New Jersey, 08854, USA

    Jae Yoon Jeon

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  1. Thiruganesh Ramasamy
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  2. Tuan Hiep Tran
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Corresponding authors

Correspondence to Han-Gon Choi, Chul Soon Yong or Jong Oh Kim.

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Ramasamy, T., Tran, T.H., Cho, H.J. et al. Chitosan-Based Polyelectrolyte Complexes as Potential Nanoparticulate Carriers: Physicochemical and Biological Characterization. Pharm Res 31, 1302–1314 (2014). https://doi.org/10.1007/s11095-013-1251-9

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  • DOI: https://doi.org/10.1007/s11095-013-1251-9

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