Evaluation of the Cytotoxic Activity and Anti-Migratory Effect of Berberine–Phytantriol Liquid Crystalline Nanoparticle Formulation on Non-Small-Cell Lung Cancer In Vitro

Abstract

Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer, which is a leading cause of cancer-related deaths worldwide. Berberine is an isoquinoline alkaloid that is commercially available for use as a supplement for the treatment of diabetes and cardiovascular diseases. However, the therapeutic benefits of berberine are limited by its extremely low bioavailability and toxicity at higher doses. Increasing evidence suggests that the incorporation of drug compounds in liquid crystal nanoparticles provides a new platform for the safe, effective, stable, and controlled delivery of the drug molecules. This study aimed to formulate an optimized formulation of berberine–phytantriol-loaded liquid crystalline nanoparticles (BP-LCNs) and to investigate the in vitro anti-cancer activity in a human lung adenocarcinoma A549 cell line. The BP-LCN formulation possessing optimal characteristics that was used in this study had a favorable particle size and entrapment efficiency rate (75.31%) and a superior drug release profile. The potential mechanism of action of the formulation was determined by measuring the mRNA levels of the tumor-associated genes PTEN, P53, and KRT18 and the protein expression levels with a human oncology protein array. BP-LCNs decreased the proliferation, migration, and colony-forming activity of A549 cells in a dose-dependent manner by upregulating the mRNA expression of PTEN and P53 and downregulating the mRNA expression of KRT18. Similarly, BP-LCNs also decreased the expression of proteins related to cancer cell proliferation and migration. This study highlights the utility of phytantriol-based LCNs in incorporating drug molecules with low GI absorption and bioavailability to increase their pharmacological effectiveness and potency in NSCLC.

Agarwood Oil Nanoemulsion Attenuates Cigarette Smoke-Induced Inflammation and Oxidative Stress Markers in BCi-NS1.1 Airway Epithelial Cells

“…The cell viability of BCiNS1.1 cells was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT, Merck, Rahway, NJ, USA), as described previously [ 69 ]. The cells were treated with different concentrations of agarwood-NE (10–1000 µg/mL) for 24 h in a 96-well plate.…”

Phytantriol-Based Berberine-Loaded Liquid Crystalline Nanoparticles Attenuate Inflammation and Oxidative Stress in Lipopolysaccharide-Induced RAW264.7 Macrophages

“…The experiments were carried out in the DMEM both in the presence and absence of berberine-phytantriol LCNs maintained at a temperature of 37 °C with 5% CO2. BP-LCN formulations were prepared as described previously [ 39 ].…”

“…Subsequently, PBS was used to wash the cells (2X), and were lysed using the TRI reagent (Merck). The next step involved the total isolation of RNA [ 39 ]. The purity and the concentration of RNA were measured by Nanodrop One (Thermo Fisher Scientific, North Ryde, NSW, Australia).…”

“…In this context, our research group has recently demonstrated significant in vitro anticancer action of berberine-loaded LCN formulation against non-small-cell lung cancer (NSCLC) cells [ 37 , 38 ]. Furthermore, we showed that a berberine-phytantriol LCN formulation possessed strong in vitro cytotoxic and anti-migratory activity against NSCLC [ 39 ]. In another study, we showed that berberine-loaded LCNs were highly effective in attenuating oxidative stress, senescence, and inflammation triggered by cigarette smoke in an in vitro model of COPD obtained by exposing mouse macrophage cells (RAW264.7) and human broncho-epithelial cells (16HBE) to cigarette smoke extract [ 40 ].…”

A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment

“…These systems mainly consist of targeting ligand, a carrier system, and bioactive moiety [ 3 ]. Many nanomodules and newer fascinating devices, namely: liposomes, polymeric nanoparticles, dendrimers or lipidic nanoparticles, polymer–lipid hybrid nanoparticles (PLNs), micelles, carbon nanotubes, and nanotubes have been crafted for enhancing the transport of therapeutic cargo to treat the tumor cells [ 4 , 5 , 6 ]. These nanoparticles have been used for drug administration by combining the advantages of polymeric core particles, liposomes, and polymer–lipid–PEG hybrids [ 7 ].…”