Work

Smart hyaluronated micelles to enhance a gemcitabine prodrug efficacy

Year: 2024

Type: article

Abstract: Self-assembling drug delivery systems have drawn attention over recent decades thanks to their versatility and easy preparation processes.Of the various nanocarriers available, micelles are able to self-assemble from an amphiphilic molecule in an aqueous solution, making them simple to prepare.In this work, 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (PEG-DSPE) was utilized to prepare lipid-based micelles for the encapsulation of a gemcitabine prodrug, GemC18, with the aim of improving its anticancer activity.Furthermore, an active targeting strategy was achieved by preparing Gem-C18-loaded PEG-DSPE micelles in the presence of a hyaluronic acid (4800 or 14,800 Da) (HA)-phospholipid conjugate (HA-DPPE) to provide actively targeted mixed micelles.This study presents the characterization of the mixed micelles, from basic characteristics (size, PDI, and zeta potential) to complex molecular structure (FESEM, X-ray diffraction, SAXS), and demonstrates that the presence of the HA-conjugate does not alter the physicochemical properties of the PEG-DSPE micelles.The mixed micelles display a size of below 100 nm, a negative zeta potential of -30 mV, and a high encapsulation efficiency (above 90 %).Finally, their preferential uptake, and consequently their cytotoxicity on cancer cell lines that overexpress the HA-specific receptor (CD44), has been assessed and confirmed using competition assays.

Source: Journal of Drug Delivery Science and Technology

DOI: 10.1016/j.jddst.2024.106518