The tumoricidal effects of etoposide incorporated into lipid nanoparticles after single-dose administration were investigated in Dalton's lymphoma ascites bearing mice. Etoposide and its nanoparticle formulations were administered intraperitoneally, and the cell cycle perturbation, cytogenetic damage, cell death (apoptosis), tumor regression, and animal survival were investigated as parameters of response with time. The tumor burden of mice treated with etoposide and its nanoparticle formulations decreased significantly (P < .001) compared with the initial up to 4 to 6 days, followed by an increase at later time intervals. Of the 3 different formulations, the survival time of mice was higher when treated with etoposide-loaded tripalmitin (ETP) nanoparticles, followed by etoposide-loaded glycerol monostearate (EGMS) (27.3%) and etoposide-loaded glycerol distearate (EGDS) (27.3%) compared with free etoposide. Cell cycle analysis revealed the hypodiploid peak (sub G0/G1 cell population) as well as G2 arrest in mice treated with etoposide and its nanoparticle formulations. The frequency of dead cells treated with the nanoparticle formulations remained high even after 8 days of treatment compared with free etoposide. The mice treated with nanoparticle formulations exhibited hypodiploid peaks and reduced S phase even 8 days after treatment, whereas the free etoposide-treated mice showed decrease in apoptosis after 3 days of treatment. The apoptotic frequency in cells 17 days after treatment was in the order of ETP > EGMS > EGDS > etoposide. The experimental results indicated that among the 3 nanoparticle formulations studied, the ETP nanoparticles showed greater and prolonged apoptotic induction properties, resulting in the higher increase in survival time of tumor bearing mice.
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http://dx.doi.org/10.1007/BF02854895 | DOI Listing |
Anal Chem
January 2025
School of Chemical Engineering, The University of Adelaide, North Terrace, Adelaide 5005, Australia.
The rise in the popularity of lipid nanoparticle (LNP)-based formulations necessitates the need for screening tools to quickly predict their colloidal stability in the presence of common excipients. Protein chemists have employed the diffusion interaction parameter () determined using dynamic light scattering as an indicator of formulation stability, yet this approach has not been applied to particulate systems. Herein, measurements of LNPs revealed behavior dissimilar to that of proteins.
View Article and Find Full Text PDFSoft Matter
January 2025
INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine (RNM), FMTS, Université de Strasbourg, F-67000 Strasbourg, France.
Characterization of nanoscale formulations is a continuous challenge. Size, morphology and surface properties are the most common characterizations. However, physicochemical properties inside the nanoparticles, like viscosity, cannot be directly measured.
View Article and Find Full Text PDFFront Immunol
January 2025
RNAimmune, Inc., Germantown, MD, United States.
Background: The unrelenting emergence of SARS-CoV-2 variants has significantly challenged the efficacy of existing COVID-19 vaccines. Enhancing the stability and immunogenicity of the spike protein is critical for improving vaccine performance and addressing variant-driven immune evasion.
Methods: We developed an mRNA-based vaccine, RV-1730, encoding the Delta variant spike protein with the S6P mutation to enhance stability and immunogenicity.
ACS Appl Bio Mater
January 2025
School of Pharmacy, Shenyang Key Laboratory of Functional Drug Carrier Materials, Shenyang Pharmaceutical University, Shenyang 110016, China.
A multifunctional nanoplatform integrating multiple therapeutic functions may be an effective strategy to realize satisfactory therapeutic efficacy in the treatment of tumors. However, there is still a certain challenge in integrating multiple therapeutic agents into a single formulation using a simple method due to variations in their properties. In this work, multifunctional CuS-ICG@PDA-FA nanoparticles (CIPF NPs) with excellent ability to produce reactive oxygen species and photothermal conversion performance are fabricated by a simple and gentle method.
View Article and Find Full Text PDFToxicol Pathol
January 2025
Johnson & Johnson Innovative Medicine, La Jolla, California, USA.
Small interfering RNAs (siRNAs) have been successfully used as therapeutics to silence disease-causing genes when conjugated to ligands or formulated in lipid nanoparticles to target relevant cell types for efficacy while sparing other cells for safety. To support the development of new methods for delivery of siRNA therapeutics, we developed and characterized a panel of antibodies generated against chemically modified nucleotides used in therapeutic siRNA molecules, identifying a monoclonal antibody that detects a broad range of siRNA representing distinct sequences and modification patterns. By integrating this anti-siRNA antibody with additional reagents, we created a multiplex siRNA immunoassay that simultaneously quantifies siRNA uptake, trafficking, and silencing activity.
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