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In Vitro and In Vivo Anticancer Activity of a Novel Nano-sized Formulation Based on Self-assembling Polymers Against Pancreatic Cancer

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ABSTRACT

Purpose

To evaluate the in vitro and in vivo pancreatic anticancer activity of a nano-sized formulation based on novel polyallylamine grafted with 5% mole cholesteryl pendant groups (CH5-PAA).

Methods

Insoluble novel anticancer drug, Bisnaphthalimidopropyldiaaminooctane (BNIPDaoct), was loaded into CH5-PAA polymeric self-assemblies by probe sonication. Hydrodynamic diameters and polydispersity index measurements were determined by photon correlation spectroscopy. The in vitro cytotoxicity evaluation of the formulation was carried out by the sulforhodamine B dye assay with human pancreatic adenocarcinoma BxPC-3 cells, while for the in vivo study, Xenograff mice were used. In vitro apoptotic cell death from the drug formulation was confirmed by flow cytometric analysis.

Results

The aqueous polymer-drug formulation had a mean hydrodynamic size of 183 nm. The drug aqueous solubility was increased from negligible concentration to 0.3 mg mL−1. CH5-PAA polymer alone did not exhibit cytotoxicity, but the new polymer-drug formulation showed potent in vitro and in vivo anticancer activity. The mode of cell death in the in vitro study was confirmed to be apoptotic. The in vivo results revealed that the CH5-PAA alone did not have any anti-proliferative effect, but the CH5-PAA-drug formulation exhibited similar tumour reduction efficacy as the commercial drug, gemcitabine.

Conclusions

The proposed formulation shows potential as pancreatic cancer therapeutics.

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ACKNOWLEDGEMENTS

SCL is supported by a fellowship from FCT (SFRH/BPD/37880/2007). Clare Hoskins was funded by Robert Gordon University, Research Development Initiative scheme.

Conflict of Interest

The authors do not have any conflicts of interest to report.

Author information

Authors and Affiliations

  1. School of Pharmacy and Life Sciences, Robert Gordon University, St. Andrew Street, Aberdeen, AB25 1HG, Scotland, UK

    Clare Hoskins & Paul Kong Thoo Lin

  2. INSERM, UMR-911 CRO2, Faculté de Médecine, 27 Blv Jean MOULIN, 13385, Marseille Cedex 05, France

    Mehdi Ouaissi, Eric Mas & Dominique Lombardo

  3. IBMC—Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180, Porto, Portugal

    Sofia Costa Lima, Inês Loureirio, Anabela Cordeiro-da-Silva & Ali Ouaissi

  4. School of Pharmacy, University of Hertfordshire, College Lane, Hatfield, AL10 9AB, UK

    Woei Ping Cheng

  5. INSERM, CNRS, UMR 5235, Universite de Montpellier 2, Batiment 24-CC 107, Pl. Eugene Bataillon, 34095, Montpellier Cedex 5, France

    Ali Ouaissi

  6. Faculté de Médecine, Université Aix Marseille, Marseille, 13000, France

    Mehdi Ouaissi

Authors
  1. Clare Hoskins
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  2. Mehdi Ouaissi
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  3. Sofia Costa Lima
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  10. Paul Kong Thoo Lin
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Correspondence to Paul Kong Thoo Lin.

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Hoskins, C., Ouaissi, M., Lima, S.C. et al. In Vitro and In Vivo Anticancer Activity of a Novel Nano-sized Formulation Based on Self-assembling Polymers Against Pancreatic Cancer. Pharm Res 27, 2694–2703 (2010). https://doi.org/10.1007/s11095-010-0268-6

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  • DOI: https://doi.org/10.1007/s11095-010-0268-6

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