Prodrugs and nanomicelles to overcome ocular barriers for drug penetration

ABSTRACT

Introduction

Ocular barriers hinder drug delivery and reduce drug bioavailability. This article focuses on enhancing drug absorption across the corneal and conjunctival epithelium. Both, transporter targeted prodrug formulations and nanomicellar strategy is proven to enhance the drug permeation of therapeutic agents across various ocular barriers. These strategies can increase aqueous drug solubility and stability of many hydrophobic drugs for topical ophthalmic formulations.

Areas covered

The article discusses various ocular barriers, ocular influx, and efflux transporters. It elaborates various prodrug strategies used for enhancing drug absorption. Along with this, the article also describes nanomicellar formulation, its characteristic and advantages, and applications in for anterior and posterior segment drug delivery.

Expert opinion

Prodrugs and nanomicellar formulations provide an effective strategy for improving drug absorption and drug bioavailability across various ocular barriers. It will be exciting to see the efficacy of nanomicelles for treating back of the eye disorders after their topical application. This is considered as a holy grail of ocular drug delivery due to the dynamic and static ocular barriers, restricting posterior entry of topically applied drug formulations.

KEYWORDS:

• Ocular drug delivery
• nanomicelles
• eye diseases
• lipid prodrugs
• transporter targeted prodrugs
• SMVT
• OCT
• anti-inflammatory drugs
• cyclosporine

Article highlights

• Static and dynamic ocular barriers drastically reduce the ocular bioavailability of various therapeutic agents.

• The anterior and posterior ocular surface has a myriad of nutrient influx transporters, which can be harnessed for drug delivery to the ocular tissues. Alternatively reducing the efflux of drugs from the efflux transporters can increase the drug ocular bioavailability.

• This is a comprehensive review on two of the most clinically successful ocular drug delivery systems for anterior ocular drug delivery systems, which includes prodrug approach and nanomicellar formulations.

• Prodrugs which utilize transporter targeted mechanism for delivery into the ocular tissues. This has shown promising clinical results. The review discusses how prodrug approach of chemical modification of the parent drug can increase the absorption of drugs across the ocular tissues with examples from the literature.

• Nanomicelles are another clinically proven strategy to increase the drug absorption especially of hydrophobic drugs into the anterior ocular tissues like cornea and conjunctiva. This expert opinion also discusses about recent developments in nanomicellar drug delivery to the eye for enhancing absorption of various therapeutic agents.

• Furthermore, nanomicelles owing to their unique physical properties can be used to explore the holy grail in ocular drug delivery which is topical administration to the back-of-the eye diseases.

Acknowledgments

The authors would like to acknowledge the guidance of Dr. Gerald Wyckoff and Dr. Russell Melchert for their help in this review article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research work was funded by University of Missouri School of Graduate Studies Research Grant which was received by Vrinda Gote.