title: In vivo intraocular distribution and safety of periocular nanoparticle carboplatin for treatment of advanced retinoblastoma in humans.
abstract: OBJECTIVE
  To study the intraocular distribution and safety of polymethylmethacrylate nanoparticles loaded with carboplatin after posterior subtenon injection in humans.
  
  
  METHODS
  Prospective, interventional, comparative case series.
  
  
  METHODS
  Six patients (mean age: 26.83 ± 7.5 years), scheduled to undergo planned uniocular enucleation in an institutional setting, were randomly divided into 3 groups. Each group received a 10 mg/mL posterior subtenon injection of nanoparticle carboplatin in the eye to be enucleated. Two eyes were enucleated 6, 24 and 72 hours post injection. Intravenous blood was collected during enucleation. The concentration of carboplatin reaching various intraocular tissues was determined by inductively coupled plasma atomic emission spectroscopy. The drug toxicity in the ocular tissues was assessed by histopathology and high-resolution transmission electron microscopy.
  
  
  RESULTS
  The highest level of carboplatin was detected in retinas (8.33 ± 1.69 mg/g), up to 24 hours post treatment. The intravitreal concentration continued to increase gradually until 72 hours (3.46 ± 0.26 mg/g). The choroids and lenses showed very low levels of carboplatin after 6 hours, with negligible amounts at 72 hours. No signs of tissue damage were observed on histopathology or electron microscopy. Intravenous concentration of carboplatin was undetectable in all patients.
  
  
  CONCLUSIONS
  Results may indicate an increased facilitated trans-scleral transport of nanoparticle carboplatin, with a sustained-release behavior but without any associated short-term ocular or systemic side effects in humans. The very high concentrations achieved in vitreous and retina after a single posterior subtenon injection may be clinically useful for adjunctive treatment of advanced intraocular retinoblastoma with vitreous seeds. However, further studies are needed to assess long-term toxicity and clinical efficacy.
authors: Department of Chemical Engineering, Indian Institute of Technology, Mumbai, India.
authors: Dhrubajyoti
authors: D
authors: Kalita
authors: Department of Facial Plastic Surgery and Ocular Oncology, Apollo Hospitals, Hyderabad, India. Electronic address: debrajshome@gmail.com.
authors: Debraj
authors: D
authors: Shome
authors: Department of Pediatrics, Mahatma Gandhi Mission Medical College and Hospital, Mumbai, India.
authors: Viral G
authors: VG
authors: Jain
authors: Department of Pathology, Metropolis Healthcare, Mumbai, India.
authors: Kirti
authors: K
authors: Chadha
authors: Department of Chemical Engineering, Indian Institute of Technology, Mumbai, India; Department of Biosciences and Bioengineering, Indian Institute of Technology, Mumbai, India.
authors: Jayesh R
authors: JR
authors: Bellare
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D001692:Biological Transport; D016190:Carboplatin / Q000009:adverse effects / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004337:Drug Carriers; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D056965:Injections, Intraocular; D008297:Male; D053758:Nanoparticles; D011446:Prospective Studies; D012160:Retina / Q000378:metabolism; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D012175:Retinoblastoma / Q000188:drug therapy / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D014822:Vitreous Body; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016190:Carboplatin