title: Incorporation of lapatinib into lipoprotein-like nanoparticles with enhanced water solubility and anti-tumor effect in breast cancer.
abstract: OBJECTIVE
  The poor water solubility of many active compounds is a serious deterrent to their use as commercial drugs. Lapatinib is a dual inhibitor of the EGF receptor and EGF receptor 2 approved by the US FDA to treat advanced breast cancer. This study prepares lapatinib-incorporated lipoprotein-like nanoparticles (LTNPs) to enhance the water solubility and elevate the anti-tumor effect of lapatinib.
  
  
  METHODS
  Bovine albumin was used to bind with lapatinib, and egg yolk lecithin was used to stabilize the conjugation of bovine albumin and lapatinib. The characteristics of LTNPs were evaluated by several experiments. Cell uptake and toxicity were performed on BT-474 cells. In vivo anti-tumor effect was performed on BT-474 xenograft-bearing mice.
  
  
  RESULTS
  LTNPs contained a lipid corona and a core of lapatinib and albumin. LTNPs could be effectively taken up by BT-474 cells and induced apoptosis. An in vivo study demonstrated that LTNPs could passively distribute into a tumor via the enhanced permeability and retention effect and induce anti-tumor activity in breast cancer.
  
  
  CONCLUSIONS
  The authors present a convenient nanoformulation with improved anti-tumor effect, which is a promising candidate for clinical trials.
authors: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, 826 Zhangheng Road, Shanghai 201203, China.
authors: Huile
authors: H
authors: Gao
authors: Shilei
authors: S
authors: Cao
authors: Chen
authors: C
authors: Chen
authors: Shijie
authors: S
authors: Cao
authors: Zhi
authors: Z
authors: Yang
authors: Zhiqing
authors: Z
authors: Pang
authors: Zhangjie
authors: Z
authors: Xi
authors: Shuaiqi
authors: S
authors: Pan
authors: Qizhi
authors: Q
authors: Zhang
authors: Xinguo
authors: X
authors: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008074:Lipoproteins / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011799:Quinazolines / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D008074:Lipoproteins; D011799:Quinazolines; D000077341:Lapatinib; D066246:ErbB Receptors