Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: An animal trial.
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Date
2014-05
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Abstract
Purpose: 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). Design: Experimental, comparative, animal study.
Materials and 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). Conclusion: 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 effi cacy
in the treatment for advanced clinical RB, specifi cally those with vitreous seeds.
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Keywords
Carboplatin, intra-vitreal concentration, nanoparticle, peri-ocular injection, polymethylmethacrylate, retinoblastoma, subconjunctival
Citation
Shome Debraj, Kalita Dhrubajyoti, Jain Viral, Sarin Rajiv, Maru Girish B, Bellare Jayesh R. Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: An animal trial. Indian Journal of Ophthalmology. 2014 May ; 62 (5): 585-589.