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Dendrimer-like AB2-type star polymers as nanocarriers for doxorubicin delivery to breast cancer cells: synthesis, characterization, in-vitro release and cytotoxicity studies

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Abstract

Novel Pentaerythritol (PTL)- and dipentaerythritol (DPTL)-cored dendrimer-like star polymers with AB2 miktoarms [A = poly(L-Lactide); poly(ethylene glycol)-folate] (1g and 2g) were synthesized and characterized by proton magnetic resonance spectroscopy, fourier transform infrared, gel permeation chromatography and differential scanning calorimetric techniques. Anticancer drug doxorubicin was encapsulated into the star polymer nanoparticles using nanoprecipitation technique. The doxorubicin-loaded nanoparticles of the star polymer with PTL core (1g-NPs-DOX) and DPTL core (2g-NPs-DOX) were spherical and had average diameters of 185.88 ± 27.53 nm and 203.66 ± 20.69 nm, and zeta potential of −19.54 ± 0.57 mV and − 14.77 ± 1.16 mV, respectively. 2g-NPs-DOX had higher doxorubicin loading and encapsulation efficiency (14.59% ± 0.001; 87.54% ± 0.003) than those of 1g-NPs-DOX (12.88% ± 0.006; 77.29% ± 0.039). In vitro release studies showed that an initial burst release of doxorubicin was followed by a sustained release over 7 days, which were significantly higher at pH 5.3 than at pH 7.4. Both drug-free nanoparticles 1g-NPs and 2g-NPs exhibited low cytotoxic effect against MCF-7 and MCF-10a with over 80% cell viability at maximum concentration (100 μM) after 72 h of incubation. Due to sustained release, the IC50 values (72 h) of 1g-NPs-DOX and 2g-NPs-DOX against MCF-7 cells were 22.5 μM and 19.5 μM respectively, as compared to 41.0 μM and 32.0 μM against MCF-10a cells, which suggested that 1g-NPs-DOX and 2g-NPs-DOX are more effective in inhibiting the breast cancer cell viability. Hence, the dendrimer-like star polymers, 1g and 2g, showed good potential as nanocarriers for preferential delivery of doxorubicin to the breast cancer cells.

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Acknowledgements

The authors would like to thank the Malaysian government for financial support through the Ministry of Science, Technology, and Innovation (MOSTI) e-Sci Fund (Grant No. 06-02-09-SF0038). We would also like to thank Yin Zhuang Ng for her assistance in repeating MTT assay.

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Authors and Affiliations

  1. School of Postgraduate Studies and Research, International Medical University, 57000, Kuala Lumpur, Malaysia

    See Kiat Wong

  2. Department of Chemistry, Universiti Pendidikan Sultan Idris, 35900, Tanjung Malim, Perak, Malaysia

    Ismail Zainol

  3. School of Liberal Arts and Sciences, Taylor’s University, Lakeside Campus, 47500, Subang Jaya, Malaysia

    Mei Peng Ng

  4. School of Pharmacy, International Medical University, 57000, Kuala Lumpur, Malaysia

    Chew Hee Ng & Ing Hong Ooi

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  1. See Kiat Wong
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Correspondence to Ing Hong Ooi.

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Wong, S.K., Zainol, I., Ng, M.P. et al. Dendrimer-like AB2-type star polymers as nanocarriers for doxorubicin delivery to breast cancer cells: synthesis, characterization, in-vitro release and cytotoxicity studies. J Polym Res 27, 190 (2020). https://doi.org/10.1007/s10965-020-02089-2

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