Comparison of ocular pharmacokinetics of etoposide and its nanoemulsion after subtenon administration in rabbits

Santosh Kumar Patnaik; Nabanita Halder; Bhavna Chawla; Deepti Maithani; Vasantha Thavaraj; Nihar Ranjan Biswas; Thirumurthy Velpandian

doi:10.1515/jbcpp-2018-0108

Article

Comparison of ocular pharmacokinetics of etoposide and its nanoemulsion after subtenon administration in rabbits

Santosh Kumar Patnaik , Nabanita Halder , Bhavna Chawla , Deepti Maithani , Vasantha Thavaraj , Nihar Ranjan Biswas and Thirumurthy Velpandian

Published/Copyright: September 9, 2019

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 30 Issue 5

Abstract

Background

Subtenon anticancer drugs are given as an adjunct to systemic chemotherapy for conditions like retinoblatoma. This study evaluated the ocular kinetics of nano-emulsion formulation of etoposide (NanoEt) and compared it with an equal dose of commercially available alcohol-based etoposide formulation in healthy rabbits.

Methods

A nanoemulsion formulation of NanoEt was developed and then evaluated for its ocular kinetics by subtenon administration in healthy rabbits. After the sterile subtenon administration of the drug, the eyes were enucleated after CO₂ euthanasia at time intervals of 2 h, 6 h, 12 h, and 24 h, and ocular tissues, blood, and plasma were separated. The concentration of etoposide in the ocular tissues and blood was quantified using liquid chromatography tandem mass spectrometry (LC MS/MS).

Results

This study found that subtenon injection of NanoEt showed 24 times higher concentration in rabbit retina compared to an equal dose of conventional marketed formulation. Based on the ocular tissue bioavailability calculations (AUC_0-24), the present study revealed that the formulation enhanced 90% ocular bioavailability of etoposide, when it was injected in the form of nano-emulsion in most of the tissues.

Conclusions

NanoEt has better bioavailability compared to the commercial alcohol-based formulation for subtenon injection. Low systemic exposure showed further advantage for its projected use in retinoblastoma (Rb) as an adjunct therapy. Further studies in Rb animal models are required to evaluate its safety and efficacy, for its clinical utility.

Keywords: chemotherapy; etoposide; nanoemulsion; retinoblastoma; subtenon injection

Funding source: Indian Council of Medical Research

Award Identifier / Grant number: 5/7/512/10-RHN

Funding statement: This research was funded by Indian Council of Medical Research, Funder Id: http://dx.doi.org/10.13039/501100001411, Grant Number: 5/7/512/10-RHN.

Acknowledgments

The authors are highly grateful to the Indian Council of Medical Research for providing financial support for conducting the research work.

Author contributions: All authors accepted responsibility for the entire content of this submitted manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Ethical approval: Involving animals complies with all relevant national regulations and institutional policies (xxxx) for the care and use of animals (xxx-Nr.: xx/x).

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Received: 2018-06-15

Accepted: 2019-07-12

Published Online: 2019-09-09

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2018-0108

Keywords for this article

chemotherapy; etoposide; nanoemulsion; retinoblastoma; subtenon injection