Subconjunctival nanoparticle carboplatin in the treatment of murine retinoblastoma.

Abstract

OBJECTIVE:

To evaluate the efficacy of subconjunctival nanoparticle carboplatin in the treatment of transgenic murine retinoblastoma.

METHODS:

Dendrimeric nanoparticles loaded with carboplatin were prepared. Forty LHbeta-Tag mice were randomly assigned into 4 groups and treated at 10 weeks of age. Each mouse received a single subconjunctival injection in one eye, and the opposite eye was left untreated as a control. Group 1 (high-dose nanoparticle carboplatin) received 37.5 mg/mL of nanoparticle carboplatin; group 2 (low-dose nanoparticle carboplatin) received 10 mg/mL of nanoparticle carboplatin; group 3 (conventional carboplatin) received 10 mg/mL of carboplatin in aqueous solution; and group 4 (phosphate-buffered saline) received phosphate-buffered saline. Mice were killed on day 22 after treatment. Eyes were serially sectioned, and retinal tumor burden was quantified by histopathologic analysis.

RESULTS:

Mean tumor burden in the treated eyes was significantly smaller compared with the untreated eyes in the same mice in both nanoparticle carboplatin groups (group 1, P = .02; group 2, P = .02) and the treated eyes in the conventional carboplatin group (group 1 vs group 3, P < .01; group 2 vs group 3, P = .01) and phosphate-buffered saline group (group 1 vs group 4, P < .01; group 2 vs group 4, P = .01). The untreated eyes in the high-dose nanoparticle carboplatin group showed significantly smaller tumor mass compared with the conventional carboplatin (P = .03) and PBS (P = .04) groups. No toxic effects were observed in any of the groups.

CONCLUSION:

A single injection of subconjunctival nanoparticle carboplatin was effective in the treatment of transgenic murine retinoblastoma, with no associated toxic effects. The higher dose of subconjunctival nanoparticle carboplatin decreased the tumor burden in the contralateral eye.

CLINICAL RELEVANCE:

This model provides a basis to test carboplatin nanoparticles for the treatment of human retinoblastoma.

• Authors: Shin J Kang, Chandrasekar Durairaj, Uday B Kompella, Joan M O'Brien, Hans E Grossniklaus
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 127 Issue 8 Pg. 1043-7 (Aug 2009) ISSN: 1538-3601 [Electronic] United States
• PMID: 19667343 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biocompatible Materials
• Dendrimers
• PAMAM G3.5 dendrimer
• Carboplatin

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Biocompatible Materials
• Carboplatin (administration & dosage)
• Conjunctiva
• Dendrimers
• Disease Models, Animal
• Drug Delivery Systems
• Injections
• Mice
• Mice, Transgenic
• Nanoparticles
• Retinal Neoplasms (drug therapy, pathology)
• Retinoblastoma (drug therapy, pathology)
• Treatment Outcome