title: Uptake and cytotoxicity of docetaxel-loaded hyaluronic acid-grafted oily core nanocapsules in MDA-MB 231 cancer cells.
abstract: OBJECTIVE
  It is hypothesized that docetaxel (Doc)-loaded hyaluronic acid (HA)-polyethylene glycol/poly(ε-caprolactone)-grafted oily core nanocapsules (NCs) can enhance the drug cytotoxicity and uptake in CD44 expressing breast cancer (BC) cells (MDA-MB 231).
  
  
  METHODS
  NCs were prepared, optimized and characterized by dynamic light scattering, transmission electron microscopy (TEM), and powder X-ray diffraction (PXRD). In vitro cytotoxicity tests [MTS, level of reactive oxygen species (ROS) and level of reduced glutathione (GSH)] were performed in BC cells. The contribution of CD44 to the NCs cellular uptake was elucidated using an anti CD44 antibody blockage and a CD44 negative NIH3T3 cell line.
  
  
  RESULTS
  The optimum formulation of Doc-loaded HA oily core NCs had respective mean diameter, polydispersity, and drug encapsulation efficiency of 224.18 nm, 0.32, and 60.38%. The NCs appeared spherical with low drug crystallinity, while the drug release data fitted to first order equation. Compared to that of ungrafted NCs, the cytotoxicity of Doc-loaded HA-grafted NCs was significantly enhanced (p<0.05). A decrease of the intracellular level of ROS was reversely correlated with that of GSH. Interestingly, the cellular internalization of HA-grafted NCs mediated CD44 was dramatically enhanced (3 to 4-fold) with respect to the absence of specific biomarker or targeting ligand.
  
  
  CONCLUSIONS
  The use of HA-grafted NCs enhanced the selective drug payload, cytotoxicity and uptake in MDA-MB 231 cells. Therefore, it could be a promising template for safe and effective delivery of Doc and similar chemotherapeutic agents in cancer cells.
authors.affiliation: Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, Division of Pharmaceutical Sciences, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108, USA.
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Youm
authors.forename: Vivek
authors.initials: V
authors.lastname: Agrahari
authors.forename: James B
authors.initials: JB
authors.lastname: Murowchick
authors.forename: Bi-Botti C
authors.initials: BB
authors.lastname: Youan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D053769:Nanocapsules; D017382:Reactive Oxygen Species; D043823:Taxoids; D000077143:Docetaxel; D006820:Hyaluronic Acid