title: Ovarian cancer targeted hyaluronic acid-based nanoparticle system for paclitaxel delivery to overcome drug resistance.
abstract: OBJECTIVE
  Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid (HA). Paclitaxel (PTX) is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including ovarian cancer. This study aimed to develop a HA-based PTX-loaded nanoparticle system to improve the ovarian cancer therapeutic effects.
  
  
  METHODS
  PTX-loaded cationic nanostructured lipid nanoparticles (PTX-NLCs) were prepared. HA-PE was then coated onto the PTX-NLCs by electrostatic adsorption to form HA-PTX-NLCs. In vitro tumor cell inhibition efficiency was analyzed on SKOV3 human ovarian cancer cells (SKOV3 cells) and PTX-resistant SKOV3 cells (SKOV3/PTX cells). In vivo anticancer ability was evaluated with mice bearing SKOV3 ovarian cancer cells xenografts.
  
  
  RESULTS
  HA-PTX-NLCs had an average diameter of 163 nm, and PTX was incorporated with an efficiency of over 80%. The in vitro viability of SKOV3 cells and SKOV3/PTX cells was obviously inhibited by HA-PTX-NLCs. In the ovarian cancer cells model, significant reduction in tumor growth was observed, whereas the conventional PTX injection group did not achieve significance.
  
  
  CONCLUSIONS
  This study demonstrated that significantly improved results were obtained by the newly constructed HA-PTX-NLCs, in terms of in vitro and in vivo therapeutic efficacy. These findings strongly support the superiority of HA based nano-system for the PTX delivery, thus enhance the efficacy of ovarian cancer chemotherapy.
authors.affiliation: a Department of Gynecology and Obstetrics , The Fourth People's Hospital of Ji'nan , Ji'nan, Shandong , People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Department of Gynecology and Obstetrics , The Fourth People's Hospital of Ji'nan , Ji'nan, Shandong , People's Republic of China.
authors.forename: Erxia
authors.initials: E
authors.lastname: Jia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D006820:Hyaluronic Acid; D017239:Paclitaxel
keywords: Drug resistance; hyaluronic acid; lipid nanoparticles; ovarian cancer; paclitaxel delivery