Folate-targeted etoposide-encapsulated lipid nanospheres

Abstract

Lipid nanospheres (LN) are simple colloidal drug delivery systems, which are proven to be useful for the systemic delivery of lipophilic anticancer drugs. Our previous work shows that the encapsulation of etoposide in LN improved the anticancer activity and a further inclusion of polyethylene glycol-distearoylphosphatidylethanolamine (DSPE-PEG) increased the circulation time and stability of LN. The present study is focused on the targeting ability of LN using Folate-PEG-DSPE. Folate-targeted (Fol-LNE) and non-targeted (SLNE) etoposide-encapsulated lipid nanospheres were prepared with the help of soybean oil, egg phosphatidylcholine, and PEG-DSPE with and without Folate-PEG-DSPE. The anticancer activity of these formulations was assessed in KB cell line. Cell uptake studies were carried out in KB cell lines using fluorescent-labeled targeted (Fol-LN) and non-targeted (SLN) lipid nanospheres without etoposide. Confocal microscopy and flow cytometry results found that, Fol-LN was selectively taken up by the KB cells and the addition of 1 mM folic acid completely blocked this uptake. Cytotoxicity results support the above finding, the IC50 values of etoposide solution, Fol-LNE, and Fol-LNEcomp (competition with 1 mM folic acid) were 33, 5, and 19 mM, respectively. Tissue distribution of Fol-LNE was compared with that of SLNE and etoposide commercial formulation (ETP) in normal mice. The studies show that in the kidney etoposide concentration was higher following Fol-LNE administration than SLNE and ETP.

Applied Nanotechnology and Nanoscience in Orthopedic Oncology

“…Finally, the entire complex is endocytosed and therefore the chemotherapeutic agent is driven directly into targeted cells. 4 Examples of such surface ligands include monoclonal antibodies, 10 mannose, 12 folic acid, 13 and ferritin. 14 Examples of Drug-Loaded Nanostructures Against Tumor Cells.…”

Crosstalk of ER Stress, Mitochondrial Membrane Potential and ROS Determines Cell Death Mechanisms Induced by Etoposide Loaded GelatinNanoparticles in MCF-7 Breast Cancer Cells

“…Since polymeric nanocarriers do not have their own cytotoxicity they can help optimize the therapeutic efficacy and greatly reduce the side effects of systemic chemotherapy [13]. Several carrier systems including liposomes, micelles, microcapsules, macromolecules, lipid emulsions, and solid lipid nanoparticles, have been evaluated for effective chemotherapy to deliver antitumor agents to target sites [14]. The purpose of the present investigation was to synthesize and characterize EGNPs (Etoposide loaded Gelatin Nanoparticles) and to evaluate their influence on the proliferation, cellular uptake in MCF-7 and HEK-293 cell line.…”

Development and Evaluation of Sustained-Release Etoposide-Loaded Poly(ε-Caprolactone) Implants

“…Attempts have been made to overcome the limitations of the formulations available in the market. Several reports have described the development of drug delivery systems containing etoposide, such as polymeric nanoparticles (13,15,16), microemulsion (17), solid lipid nanoparticles (18,19), and microspheres (20,21). However, polymeric implants consisting of etoposide and PCL have not been reported to date.…”