In vivo intraocular distribution and safety of periocular nanoparticle carboplatin for treatment of advanced retinoblastoma in humans

Abstract

Purpose: To study the intraocular distribution and safety of polymethylmethacrylate nanoparticles loaded with carboplatin after posterior subtenon injection in humans.

Design: 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.

Conclusion: 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.