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Effects of Particle Size and Surface Modification on Cellular Uptake and Biodistribution of Polymeric Nanoparticles for Drug Delivery

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ABSTRACT

Purpose

To investigate the effects of the particle size and surface coating on the cellular uptake of the polymeric nanoparticles for drug delivery across the physiological drug barrier with emphasis on the gastrointestinal (GI) barrier for oral chemotherapy and the blood–brain barrier (BBB) for imaging and therapy of brain cancer.

Methods

Various sizes of commercial fluorescent polystyrene nanoparticles (PS NPs) (viz 20 50, 100, 200 and 500 nm) were modified with the d-α-tocopheryl polyethylene glycol 1,000 succinate (vitamin E TPGS or TPGS). The size, surface charge and surface morphology of PS NPs before and after TPGS modification were characterized. The Caco-2 and MDCK cells were employed as an in vitro model of the GI barrier for oral and the BBB for drug delivery into the central nerve system respectively. The distribution of fluorescent NPs after i.v. administration to rats was analyzed by the high performance liquid chromatography (HPLC).

Results

The in vitro investigation showed enhanced cellular uptake efficiency for PS NPs in both of Caco-2 and MDCK cells after TPGS surface coating. In vivo investigation showed that the particle size and surface coating are the two parameters which can dramatically influence the NPs biodistribution after intravenous administration. The TPGS coated NPs of smaller size (< 200 nm) can escape from recognition by the reticuloendothelial system (RES) and thus prolong the half-life of the NPs in the blood system.

Conclusions

TPGS-coated PS NPs of 100 and 200 nm sizes have potential to deliver the drug across the GI barrier and the BBB.

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ACKNOWLEDGMENTS AND DISCLOSURES

This work is supported by the Singapore–China Cooperative Research Project between Agency of Science, Technology and Research (A*STAR), Singapore and Chinese Ministry of Science and Technology (MOST) (R-398-000-077-305, PI: Feng SS) and the NUS FSF grant R-397-000-136-731 and FRC grant (R-397-000-136-112, Co-PI: Feng SS). SAK would like to thank NanoCore for providing the postdoctoral fellowship. As well as Dr V. Gopal and Dr M.S. Muthu for valuable discussions and Mr C.W. Gan, Mr W.M. Phyo, Mr P. Chandrasekharan and Ms S.Y. Chaw for their kind help in experiments.

The authors report no conflict of interest.

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Authors and Affiliations

  1. Department of Chemical & Biomolecular Engineering, National University of Singapore, Block E5, 02-11 4 Engineering Drive 4, Singapore, 117576, Singapore

    Sneha A. Kulkarni & Si-Shen Feng

  2. NanoCore, National University of Singapore, Block EA, 04-27, 9 Engineering Drive 1, Singapore, 117576, Singapore

    Sneha A. Kulkarni & Si-Shen Feng

  3. Department of Bioengineering, National University of Singapore, Block EA, 05-12, 9 Engineering Drive 1, Singapore, 117576, Singapore

    Si-Shen Feng

  4. Nanoscience & Nanoengineering Initiative (NUSNNI) & NanoCore, National University of Singapore, Block E3, 05-29 2 Engineering Drive 3, Singapore, 117581, Singapore

    Si-Shen Feng

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  1. Sneha A. Kulkarni
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Correspondence to Si-Shen Feng.

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Kulkarni, S.A., Feng, SS. Effects of Particle Size and Surface Modification on Cellular Uptake and Biodistribution of Polymeric Nanoparticles for Drug Delivery. Pharm Res 30, 2512–2522 (2013). https://doi.org/10.1007/s11095-012-0958-3

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  • DOI: https://doi.org/10.1007/s11095-012-0958-3

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