Synthesis And Characterization Of Novel PLGA And HA-Based Nanoparticle Drug Delivery System Incorporating Dactolisib And Its In Vitro Evaluation Against HCT116 Colorectal Carcinoma Cells

Abstract

Colorectal carcinoma remains a significant health concern worldwide, necessitating the development of innovative targeted therapy approaches to improve treatment outcomes. In this study, we explore the efficacy of a novel drug delivery system (DDS) utilizing poly (lactic-co-glycolic acid) (PLGA) nanoparticles conjugated with hyaluronic acid (HA) for targeted therapy against colorectal carcinoma. The DDS was formulated by encapsulating the mTOR inhibitor Dactolisib within HA-conjugated PLGA nanoparticles Various analytical techniques including Dynamic Light Scattering (DLS), Fourier-Transform Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Analysis (EDX), and cell-based assays were employed for comprehensive characterization. In vitro studies were performed to evaluate the cytotoxicity of the DDS against HCT116 colorectal carcinoma cells, compared to free Dactolisib. The HA-conjugated PLGA nanoparticles exhibited an average size of 164.3 nm with a narrow size distribution, as determined by dynamic light scattering (DLS) analysis. Transmission electron microscopy (TEM) imaging revealed a spherical morphology of the nanoparticles. Drug encapsulation efficiency was measured at 87.6%, indicating successful loading of Dactolisib within the nanoparticles. In vitro, cytotoxicity assays demonstrated a significant reduction in cell viability following treatment with the DDS, with IC50 values that changed from 113 nm to 66.91 nm at 48 hours in HCT116+ve P53 cell line, whereas DDS exhibited IC50 7.05 nm, 14.93 nm, and 32.72  compared to Dactolisib which showed IC50 values of 238.9 nm, 102.31 nm, and 20.55 nm at 24, 48, and 72 hours, respectively in the HCT116-ve P53 cell line. The DDS demonstrated superior cytotoxicity against colorectal carcinoma cells compared to free Dactolisib, attributed to efficient drug delivery and disruption of the mTOR signaling pathway.