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Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery

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Abstract

The amalgamation of chemotherapy and gene therapy is promising treatment option for cancer. In this study, novel biocompatible self-assembled nanocomplexes (NCs) between carboxylmethylated pullulan t335 (CMP) with polyallylamine (CMP–PAA NCs) were developed for plasmid DNA (pDNA) and pH-sensitive doxorubicin (DOX) delivery. DOX was conjugated to CMP (DOX–CMP) via hydrazone and confirmed by FTIR and 1H-NMR. In vitro release studies of pH-sensitive DOX–CMP conjugate showed 23 and 85 % release after 48 h at pH 7.4 (physiological pH) and pH 5 (intracellular/tumoral pH), respectively. The CMP–PAA NCs or DOX–CMP–PAA NCs self-assembled into a nanosized (<250 nm) spherical shape as confirmed by DLS and TEM. The hemolysis and cytotoxicity study indicated that the CMP–PAA NCs did not show cytotoxicity in comparison with plain polyallylamine. Gel retardation assay showed complete binding of pDNA with CMP–PAA NCs at 1:2 weight ratio. CMP–PAA NCs/pDNA showed significantly higher transfection in HEK293 cells compared to PAA/pDNA complexes. Confocal imaging demonstrated successful cellular uptake of DOX–CMP–PAA NCs in HEK293 cells. Thus, NCs hold great potential for targeted pDNA and pH-sensitive intratumoral drug delivery.

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Acknowledgments

Authors are thankful to University Grant Commission (UGC), Government of India, for financial assistance, and AICTE-NAFETIC for providing facilities to perform the experimental work.

Conflict of interest

The authors report no conflicts of interest.

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Authors and Affiliations

  1. Center for Novel Drug Delivery Systems, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University under Sect. 3 of UGC Act – 1956, Elite Status and Center of Excellence – Govt. of Maharashtra, N. P. Marg, Matunga (E), Mumbai, 400019, India

    Lalit Vora, Ketan Patel & Pradeep Vavia

  2. Gupta Lab, Cancer Research Institute, Advanced Center for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, 410210, India

    Monica Tyagi & Sanjay Gupta

Authors
  1. Lalit Vora
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  2. Monica Tyagi
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  3. Ketan Patel
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  4. Sanjay Gupta
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  5. Pradeep Vavia
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Correspondence to Pradeep Vavia.

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Vora, L., Tyagi, M., Patel, K. et al. Self-assembled nanocomplexes of anionic pullulan and polyallylamine for DNA and pH-sensitive intracellular drug delivery. J Nanopart Res 16, 2781 (2014). https://doi.org/10.1007/s11051-014-2781-8

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  • DOI: https://doi.org/10.1007/s11051-014-2781-8

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