Preparation, in vitro and in vivo evaluation of polymeric nanoparticles bas hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethy 1000 succinate for tumor-targeted delivery of morin hydrate

Herein, we describe the preparation of a targeted cellular delivery system for morin hydrate (MH), -molecular-weight hyaluronic acid-poly(butyl cyanoacrylate) (HA-PBCA) block copolymer. In ord the therapeutic effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was HA-PBCA during the preparation process. The MH-loaded HA-PBCA “plain” nanoparticle (MH-P PBCA/TPGS “mixed” nanoparticles (MH-MNs) were concomitantly characterized in terms of load particle size, zeta potential, critical aggregation concentration, and morphology. The obtained MHMNs exhibited a spherical morphology with a negative zeta potential and a particle size less than 2 favorable for drug targeting. Remarkably, the addition of TPGS resulted in about 1.6-fold increase loading. The in vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of cells compared with MH solution and MH-PNs. Furthermore, blank MNs containing TPGS exhibit cytotoxic effects against cancer cells without diminishing the viability of normal cells. In addition, uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than that of PNs, in A5 CD44 receptor competitive inhibition and the internalization pathway studies suggested that the int mechanism of the nanoparticles was mediated mainly by the CD44 receptors through a clathrin-dep endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo antitumor potency and tumor cell apoptosis than did MH-PNs, following intravenous administration to S180 tumor-bearin Overall, the results imply that the developed nanoparticles are promising vehicles for the targeted d lipophilic anticancer drugs.