Does a Nanomolecule of Carboplatin Injected Periocularly Help in Attaining Higher Intravitreal Concentrations?

Abstract

To compare intravitreal concentration (VC) of commercially available carboplatin (CAC) and the novel nanomolecule carboplatin (NMC), after periocular injection. The study was a comparative animal study involving 24 white Sprague-Dawley rats, aged between 6 weeks and 3 months. CAC was bound with a nanoparticulate carrier by co-acervation with a biocompatible and biodegradable protein BSA (bovine serum albumin). The particulate size, binding, and structure of the carrier was analyzed with dynamic light-scattering electron microscopy, FTIR (Fourier transform infrared) spectroscopy, and SDS-polyacrylamide gel electrophoresis. Twenty-four white rats were anesthetized. The right eye of each rat was injected with periocular CAC (1 mL) and the left eye with NMC (1 mL) by a trained ophthalmologist. Four mice each were euthanatized at days 1, 2, 3, 5, 7, 14, and 21 and both eyes were enucleated. The intravitreal concentrations of commercial carboplatin and nanomolecule carboplatin were determined with HPLC (high-performance liquid chromatography). Data were analyzed with the paired t-test. The main outcome measure was intravitreal concentrations CAC and NMC over time. The NMC vitreal concentration was higher than the CAC concentrations in all animals, until day 7 (P = 0.0001). On days 14 and 21, the CAC vitreal concentration was higher than the NMC concentrations in all animals (P = 0.0002). Overall, the mean vitreal concentration of NMC was greater than CAC. Nanoparticulate-bound carboplatin has greater transscleral transport than commercially available carboplatin, especially in the first week after injection and may help enhance the proven adjuvant efficacy of periocular carboplatin over and above systemic chemotherapy in treating human retinoblastoma, especially those with vitreal seeds. This trial is being published to establish a proof of principle for this method of therapy.