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Development, Optimization, and Evaluation of Nano-platforms for Delivery of siRNA and BPTES in c-Myc Induced Breast Cancer

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Abstract

Purpose

siRNA therapeutics has emerged as a promising strategy for treating several “undruggable” genetically impaired conditions while BPTES, an inhibitory molecule of the glutaminase enzyme is beneficial in treating various glutamine induced cancers. While siRNA is highly susceptible to degradation, the latter has solubility issues which hamper their delivery to the target site. Therefore, the delivery of both the components using PLGA nanoparticles can be a promising approach in treating breast cancer. Hence, the objective is to develop polymeric nanoparticles of siRNA and BPTES and to check their synergistic/additive effect in breast cancer cell lines namely MCF7 and MDA-MB231.

Methods

siRNA specific to c-Myc gene designed using siRNA designing tools. Development and optimization of polymeric nanoparticles was done using Box-Behnken design. The formulated nanoparticles were characterized for particle size, zeta potential, PDI, and encapsulation efficiency. They were also subjected to surface morphological analysis, stability studies, FTIR, XRD, in vitro release study, in vitro cytotoxicity, and checkerboard study in breast cancer cell lines.

Results

siRNA and BPTES were encapsulated within PLGA nanoformulations. The nanoparticles had particle size in the range of 200–350 nm and zeta potential of −20 to −28. SEM and TEM images confirmed their morphology. Agarose gel electrophoresis confirmed the safe incorporation of siRNA into the polymeric matrix. The in vitro release study showed the sustained release of nanoformulation for 72 h. The in vitro cytotoxicity studies and checkerboard assay confirmed the synergistic effect of the nanoformulations in breast cancer cells.

Conclusion

The siRNA and BPTES loaded nanoparticles were successfully developed which showed positive results in breast cancer cells.

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Acknowledgements

The authors are grateful and would like to acknowledge Indian Council of Medical Research (ICMR), Government of India, New Delhi for Senior Research Fellowship to Ms. Arpita Paul. The authors are grateful to ICMR, Government of India, New Delhi, and Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal for providing financial and infrastructural support for the research activities.

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  1. Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India

    Arpita Paul, Avirup Biswas, Swarnabh Chatterjee, Alan Raj & Angel Treasa Alex

  2. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India

    Ruchira Raychaudhuri & Srinivas Mutalik

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Paul, A., Biswas, A., Chatterjee, S. et al. Development, Optimization, and Evaluation of Nano-platforms for Delivery of siRNA and BPTES in c-Myc Induced Breast Cancer. J Pharm Innov 18, 2210–2234 (2023). https://doi.org/10.1007/s12247-023-09785-8

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