Hyaluronic acid-coated liposomes for active targeting of gemcitabine

Abstract

The aim of this work was the preparation, characterization and preliminary evaluation of the targeting ability towards pancreatic adenocarcinoma cells of liposomes containing the gemcitabine lipophilic prodrug [4-(N)-lauroyl-gemcitabine, C12GEM]. Hyaluronic acid (HA) was selected as targeting agent since it is biodegradable, biocompatible, can be chemically modified and its cell surface receptor CD44 is overexpressed on various tumors.For this purpose, conjugates between a phospholipid, the 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and HA of two different low molecular weights 4800 Da (12 disaccharidic units) and 12000 Da (32 disaccharidic units), were prepared, characterized and introduced in the liposomes during the preparation.Different liposomal formulations were prepared and their characteristics were analyzed: size, Z potential and TEM analyses underline a difference of the HA-liposomes from the non-HA ones. In order to better understand the HA-liposome cellular localization and to evaluate their interaction with CD44 receptor, confocal microscopy studies were performed. The results demonstrate that HA facilitates the recognition of liposomes by MiaPaCa2 cells (CD44 + ) and that the uptake increases with increasing of the polymer molecular weight.Finally, the cytotoxicity of the different preparations was evaluated and data show that incorporation of C12GEM increases their cytotoxic activity and that HA-liposomes inhibit cell growth more than plain liposomes.Altogether the results demonstrate the specificity of C12GEM targeting towards CD44-overexpressing pancreatic adenocarcinoma cell line using HA as a ligand.

Hyaluronic acid-decorated reconstituted high density lipoprotein targeting atherosclerotic lesions

“…Both EE and DL of LT in all nanocarriers were satisfactory for nanostructured lipid carriers. TEM photographs revealed that all particles of LT-NLC, LT-rHDL and HA-LT-rHDL presented spherical in shape, and the exclusively hydrophilic corona out the surface of HA-LT-rHDL could imply indirectly the successful coating of HA onto the surface of the LT-rHDL, which was analogous to Arpicco and his colleagues' work [38]. Moreover, it was obviously indicated that in vitro release profiles of LT from LT-NLC, LT-rHDL and HA-LT-rHDL all showed markedly sustained-release and complied with near zero-order sustained release (those related figures not shown here), on account that the hydrophobic core of three nanoparticles strongly confined the migration of LT into the release medium.…”

Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor

“…We may therefore assume that a portion of the multiple DOPE units bound to each HA molecule intercalates within the DOPE and DE bilayers upon liposome preparation. (25,52) The correlation between regularly spaced bilayers gives rise to a Bragg peak. A tiny peak is barely detected in the 5% HA-DOPE liposome curve.…”

Silver nanoparticles enhance the apoptotic potential of gemcitabine in human ovarian cancer cells: combination therapy for effective cancer treatment

“…To compensate those shortcomings such as high toxicity and severe side effects, here we selected a combination therapy model of GEM with AgNPs. Previously, several studies have reported (including Arpicco et al 15 ) the specificity of C12GEM targeting toward CD44-overexpressing pancreatic adenocarcinoma cell line using hyaluronic acid-coated liposomes for active targeting of GEM. Thyroid-stimulating hormone nanoliposomes encapsulated with GEM showed improved anticancer efficacy in vitro and in a tumor model of follicular thyroid carcinoma.…”