Ciprofloxacin-encapsulated solid lipid nanoparticles: a comprehensive biochemical analysis of cytotoxic effects, proliferation inhibition, and apoptotic induction in KG1-a leukemia cells.

Abstract

As a fundamental approach to the treatment of acute myeloid leukemia (AML), chemotherapeutic agents face significant clinical challenges, including poor solubility and low bioavailability. In this context, solid lipid nanoparticles (SLNs) have emerged as a promising drug delivery system in oncologic therapies, owing to their advantageous characteristics, such as enhanced physical stability and controlled drug-release profiles. This study focuses on the synthesis of ciprofloxacin (CP)-loaded SLNs, aiming to enhance the anticancer efficacy of CP, an antibiotic recognized for its potential anticancer properties, while simultaneously reducing its associated side effects. Characterization of blank SLN and CP-SLN was conducted using dynamic light scattering (DLS), atomic force microscopy (AFM), UV-Vis spectrophotometry, and Fourier transform infrared spectroscopy (FTIR). In vitro release was carried out using dialysis bag method in isotonic phosphate buffer (pH = 7.4). The anticancer and pro-apoptotic effects of the CP-SLN formulation were assessed through cell viability assays, Hoechst staining, and Annexin V/PI flow cytometry. Additionally, expression levels of Bax, Bcl2, and p53 were analyzed via Real-Time PCR. The synthesized CP-SLN formulation exhibited optimal characteristics, including a particle size of 340-360 nm, a polydispersity index (PDI) of 0.4, and an entrapment efficiency of 90%. The in vitro drug release showed an initial burst release in the time points 4-10 h. Both CP and the CP-SLN formulations demonstrated significant anti-proliferative and pro-apoptotic effects on KG1-a cells, as indicated by the upregulation of the Bax/Bcl2 ratio and p53, resulting in G0/G1 cell cycle arrest and apoptosis induction. The results suggest that encapsulating CP in SLN enhances its anticancer and pro-apoptotic effects in KG1-a stem-like leukemia cells. Thus, CP-SLN may serve as a promising formulation for leukemia treatment and could improve the efficacy of other therapeutic agents.