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

Arpita Paul, Avirup Biswas, Swarnabh Chatterjee, Alan Raj, Ruchira Raychaudhuri, Srinivas Mutalik, Angel Treasa Alex

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2210-2234
Number of pages25
JournalJournal of Pharmaceutical Innovation
Volume18
Issue number4
DOIs
Publication statusAccepted/In press - 2023

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

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