Journal of Nanomedicine & Nanotechnology

Encapsulation of etoposide in self-assembled micelles based on hydrophobized hyaluronic acid

7^th International Conference on Nanomedicine And Nanotechnology

June 28, 2023 | Webinar

Maria Antonova, Yulia Ermolenko, Nadezhda Osipova, Anna Alekseeva and Svetlana Gelperina

Mendeleev University of Chemical Technology, Russia
Research Institute of Human Morphology, Russia

Scientific Tracks Abstracts: J Nanomed Nanotechnol

Abstract:

Polymeric micelles are promising colloidal carriers for poorly water soluble and amphiphilic drugs. Among the polymers used for preparation of micellar drug formulations, the hydrophobic derivatives of hyaluronic acid (HA) are gaining special attention due to their safety and biocompatibility and, especially, because of their affinity to the CD44 receptor expressed by many malignant tumors. The purpose of this work was to develop the self-assembled micellar form of a hydrophobic antitumor drug etoposide (ETO) and its prodrug 4'-O-benzyloxycarbonyl etoposide (ETO-Cbz) based on HA grafted with C18 acyl chains (HA-C18). Methods: The micelles (ETO/HA-C18) and ETO-Cbz/HA-C18) were prepared using the solvent evaporation method. The micelle size and size distribution (PDI) were measure by dynamic light scattering. The cytotoxicity (IC50) was assessed in the human breast cancer cells MCF-7cell line. Results: The ETO/HA-C18 micelles were characterized by a slightly higher size than ETO-Cbz/HA-C18 (535 nm and 373 nm, respectively) and its encapsulation efficiency was lower (66% and 74%, respectively). In spite of their considerable negative zeta potentials (~-50 mV), both types of micelles exhibited the tendency to aggregate (PDI 0.25-0.34) (Fig. 1a). Aggregates were stable for 24 hours at room temperature in saline and in the cell culture media (DMEM and RPMI) as no increase in size was observed. Importantly, both micellar formulations demonstrated a higher cytotoxicity against the MCF-7 cells as compared to the free drugs (Fig. 1b), which could be due to the known hyperexpression of the CD44 receptor exhibited by these cells. The obtained results suggest that the HA-C18-based micellar delivery systems of ETO and its pro-drug are the promising candidates for selective chemotherapy of breast cancer. Acknowledgments: Scientific research has been carried out within the project No. 23-25-00194 of Russian Scientific Foundation. Recent publications: 1. Wang H, Sun G, Zhang Z, Ou Y (2017) Transcription activator, hyaluronic acid and tocopheryl succinate multi-functionalized novel lipid carriers encapsulating etoposide for lymphoma therapy. Biomedicine & Pharmacotherapy 91:241-250 2. Harrer D, Armengol E S, Friedl J D, Jalil A, Jelkmann M, Leichner C, Laffleur F (2021) Is hyaluronic acid the perfect excipient for the pharmaceutical need? International Journal of Pharmaceutics 601:120589 3. Du Y, Wang S, Zhang T, He D, Tu J, Shen Y (2020) Enhanced cytotoxicity of a redox-sensitive hyaluronic acid-based nanomedicine toward different oncocytes via various internalization mechanisms. Drug Delivery 27(1):128-136. 4. Lui Y, Zhou C, Wei S, Lan Y, Cao A, Yang J, Hou Y (2018) Paclitaxel delivered by CD44 receptor-targeting and endosomal pH sensitive dual functionalized hyaluronic acid micelles for multidrug resistance reversion. Colloids and Surfaces B: Biointerfaces 170:330-340 5. Al-Othman N, Alhendi A, Ihbaisha M, Barahmeh M, Alqaraleh M, Al-Momany B Z (2020) Role of CD44 in breast cancer. Breast Dis 39(1): 1–13.

Biography :

Maria Antonova is a graduate student of the Mendeleev University (Moscow) working in the field of targeting drug delivery nanosystems. Her bachelor thesis defended in 2022 was devoted to the development of the organic/inorganic colloidally stable structures based on hyaluronic acid, potentially suitable for designing theranostics. During her master project she continues working in this field. Her thesis is focused on the design and investigation of the micellar nanosystems for delivery of the hydrophobic anticancer drugs (etoposide, paclitaxel, docetaxel).