title: Hydroxycamptothecin-loaded nanoparticles enhance target drug delivery and anticancer effect.
abstract: BACKGROUND
  Hydroxycamptothecin (HCPT) has been shown to have activity against a broad spectrum of cancers. In order to enhance its tissue-specific delivery and anticancer activity, we prepared HCPT-loaded nanoparticles made from poly(ethylene glycol)-poly(gamma-benzyl-L-glutamate) (PEG-PBLG), and then studied their release characteristics, pharmacokinetic characteristics, and anticancer effects. PEG-PBLG nanoparticles incorporating HCPT were prepared by a dialysis method. Scanning electron microscopy (SEM) was used to observe the shape and diameter of the nanoparticles. The HCPT release characteristics in vitro were evaluated by ultraviolet spectrophotometry. A high-performance liquid chromatography (HPLC) detection method for determining HCPT in rabbit plasma was established. The pharmacokinetic parameters of HCPT/PEG-PBLG nanoparticles were compared with those of HCPT.
  
  
  RESULTS
  The HCPT-loaded nanoparticles had a core-shell spherical structure, with a core diameter of 200 nm and a shell thickness of 30 nm. Drug-loading capacity and drug encapsulation were 7.5 and 56.8%, respectively. The HCPT release profile was biphasic, with an initial abrupt release, followed by sustained release. The terminal elimination half-lives (t 1/2 beta) of HCPT and HCPT-loaded nanoparticles were 4.5 and 10.1 h, respectively. Peak concentrations (Cmax) of HCPT and HCPT-loaded nanoparticles were 2627.8 and 1513.5 microg/L, respectively. The apparent volumes of distribution of the HCPT and HCPT-loaded nanoparticles were 7.3 and 20.0 L, respectively. Compared with a blank control group, Lovo cell xenografts or Tca8113 cell xenografts in HCPT or HCPT-loaded nanoparticle treated groups grew more slowly and the tumor doubling times were increased. The tumor inhibition effect in the HCPT-loaded nanosphere-treated group was significantly higher than that of the HCPT-treated group (p < 0.01). Tumor inhibition in the control group by PEG-PBLG nanoparticles was not observed (p > 0.05).
  
  
  CONCLUSIONS
  Compared to the HCPT- and control-treated groups, the HCPT-loaded nanoparticle-treated group showed a more sustained release, a longer circulation time, increased delivery to tissue, and an enhanced anticancer effect. HCPT-loaded nanoparticles appear to change the pharmacokinetic behavior of HCPT in vivo.
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. anxunwang@yahoo.com
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
authors.forename: Su
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; C028098:10-hydroxycamptothecin; D002166:Camptothecin