title: In vitro and in vivo anti-tumor efficacy of 10-hydroxycamptothecin polymorphic nanoparticle dispersions: shape- and polymorph-dependent cytotoxicity and delivery of 10-hydroxycamptothecin to cancer cells.
abstract: Nanotechnology associated with a crystal engineering approach was proposed for improving the solubility and efficacy of hydrophobic drugs in this study. 10-hydroxycamptothecin polymorphic nanoparticle dispersions (HCPT-PNDs) were prepared using the supercritical anti-solvent technique coupled with the high-pressure homogenization method. Shape- and polymorph-dependent tumor suppression was observed in both in vitro and in vivo models, where needle-shaped HCPT-PND exhibited dramatic improvement of antitumor efficacy. A benefit of controllable size and a large surface-to-volume ratio of needle-shaped nanoparticles is the improvement of dissolution properties, which facilitates enhancing pharmacokinetic and pharmaco-dynamic properties. The needle-shaped HCPT-PND, which with longer blood retention time and more effective cellular uptake, makes it possible to accumulate drug in tumor tissues and exhibit higher cytotoxicity. No severe systemic toxicity was observed due to sustained-dissolution and the low dose of drug in normal tissues. The results suggest that the needle-shaped HCPT-PND is an interesting nano-formulation of HCPT.
  
  
  BACKGROUND
  Nanotechnology has enabled the production of novel therapeutics drugs against cancer. Here, the authors investigated the use of a crystal engineering approach for the modification of camptothecin in order to improve its water solubility. Physicochemical and biological properties were studied. The results would suggest the applicability of this approach for nano-formulation.
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, China.
authors.forename: Hongdi
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Feng
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, China.
authors.forename: Guijin
authors.initials: G
authors.lastname: Liu
authors.affiliation: National Engineering Research Centre of Genetic Medicine, Guangzhou, China.
authors.forename: Baoqiong
authors.initials: B
authors.lastname: Chen
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, China. Electronic address: cebjiang@scut.edu.cn.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: National Engineering Research Centre of Genetic Medicine, Guangzhou, China; College of Life Science and Technology, Jinan University, Guangzhou, China. Electronic address: txql@jnu.edu.cn.
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Xie
mesh_terms: D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D012995:Solubility; D014018:Tissue Distribution
chemical_list: C028098:10-hydroxycamptothecin; D002166:Camptothecin
keywords: 10-hydroxycamptothecin; Antitumor efficacy; Cancer therapy; Cytotoxicity; Polymorph; Shape