title: Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: an animal trial.
abstract: OBJECTIVE
  The purpose of the study is to compare the intra-vitreal concentrations of carboplatin, post peri-ocular injections of commercially available carboplatin (CAC) and a novel carboplatin loaded polymethylmethacrylate nanoparticulate carboplatin (NPC), in either eye, as a model system for treatment of advanced intra-ocular retinoblastoma (RB).
  
  
  METHODS
  Experimental, comparative, animal study.
  
  
  METHODS
  Polymethylmethacrylate nanoparticles were prepared by free radical emulsion polymerization of methyl methacrylate in aqueous solution of carboplatin in the presence of surfactant sodium dodecyl sulfate and thermal initiator ammonium persulfate. 21 Sprague-Dawley rats, aged between 6 weeks and 3 months were enrolled. The right eye of each rat was injected peri-ocularly with CAC formulation (1 ml of 10 mg/ml) and the left eye with NPC (1 ml of 10 mg/ml), post-anesthesia, by an ophthalmologist trained in ocular oncology. Three rats each were euthanized on days 1, 3, 5, 7, 14, 28 and 42, post-injection and both eyes were carefully enucleated. Intra-vitreal concentrations of CAC and NPC were determined with Inductively Coupled Plasma Atomic Emission Spectroscopy. Analysis of data was done with paired t-test.
  
  
  RESULTS
  The intra-vitreal concentration of carboplatin with NPC was ~3-4 times higher than with CAC in all animals, on all the days (P < 0.05).
  
  
  CONCLUSIONS
  A higher trans-scleral permeability gradient is obtained with the novel nanoparticles than with the commercial drug, leading to sustained higher levels of carboplatin in the vitreous. Peri-ocular injection of NPC could thus have an adjuvant efficacy in the treatment for advanced clinical RB, specifically those with vitreous seeds.
authors.affiliation: Department of Ophthalmic and Facial Plastic Surgery, Nova Specialty Surgery, Mumbai, Maharashtra, India.
authors.forename: Debraj
authors.initials: D
authors.lastname: Shome
authors.forename: Dhrubajyoti
authors.initials: D
authors.lastname: Kalita
authors.forename: Viral
authors.initials: V
authors.lastname: Jain
authors.forename: Rajiv
authors.initials: R
authors.lastname: Sarin
authors.forename: Girish B
authors.initials: GB
authors.lastname: Maru
authors.forename: Jayesh R
authors.initials: JR
authors.lastname: Bellare
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005500:Follow-Up Studies; D007262:Infusions, Intravenous; D058449:Intravitreal Injections; D053758:Nanoparticles; D009374:Neoplasms, Experimental; D019904:Polymethyl Methacrylate; D051381:Rats; D017207:Rats, Sprague-Dawley; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D012175:Retinoblastoma / Q000188:drug therapy* / Q000378:metabolism; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019904:Polymethyl Methacrylate; D016190:Carboplatin