proposed the preparation

of HA-coated nanostructured lipid carriers (HA-NLCs) for tumor targeting via electrostatic attraction [16]. In this approach, cationic NLCs loaded with PTX were prepared by melt emulsion technology, followed by coating with HA (300kDa); the process of electrostatic attraction was simple and controllable, and no chemical reagents were needed. The in vitro cytotoxicity and in vivo antitumoral activity studies showed that HA-PTX-NLCs were more effective than Taxol with fewer side effects. HA-NCL also prolonged the blood circulation time of PTX and increased its accumulation in tumors. HA-modified nanoparticles have Inhibitors,research,lifescience,medical been proposed to overcome 17-DMAG mechanism clinical limits of chemotherapeutics, such as Docetaxel (DCT). DTC is a semisynthetic taxane derivative very effective against different tumors, Inhibitors,research,lifescience,medical but its clinical use causes several side effects and other limitations regarding the appearance of multidrug resistance (MDR) and its insolubility. Recently Cho et al. described the preparation of HA-ceramide (CE) self-assembled nanoparticles for DCT and DOX active targeting [17, 49]. The in vitro cellular uptake studies showed that nanoparticles enhanced intracellular DCT Inhibitors,research,lifescience,medical uptake in the CD44-overexpressing cell lines MCF-7.

MDR-overcoming effects of DCT nanoparticles were observed in cytotoxicity test in CD44-positive MCF-7 breast cancer cells resistant to doxorubicin. The Inhibitors,research,lifescience,medical in vivo tumor targetability was evaluated using a noninvasive fluorescence imaging system in the same cells xenografted in a mouse model. To assess the uptake

mechanism by a competitive inhibition assay, CD44 receptors were blocked with preinjection of high doses of HA. The fluorescence signal in the HA preinjected animal group was lower than that in no preinjection group for 24h, indicating a probable reduction in nanoparticle uptake due to the blocking of CD44. The real-time imaging data showed that the fluorescent signal increased for the first 6h and was selleck inhibitor maintained for 1 day. Then the tumors were dissected 24h following injection, and the observed fluorescence intensity of HA Inhibitors,research,lifescience,medical pre-injection group was only 43.9% of the no preinjection group. The same research team described the preparation of DOX-loaded, self-assembled, HA-CE-PEG-based nanoparticles [18]. Entinostat In vitro tests were performed on two different cell lines with different CD44 expression: NIH3T3 (mouse embryonic fibroblast cells, CD44-negative) and SCC7 (mouse squamous cell carcinoma cells, CD44-positive). The cytotoxicity studies showed that HA-CE-based nanoparticles can be used as vehicle without important toxicity. The cellular uptake efficacy of DOX from nanoparticles via HA and CD44 interaction was demonstrated by confocal microscopy analysis. In vivo studies on SCC7 tumor xenograft mouse model showed improved retention time in the bloodstream and nanoparticle accumulation at the tumor site.