Topical application of polymeric nanomicelles in ophthalmology: a review on research efforts for the noninvasive delivery of ocular therapeutics

ABSTRACT

Introduction

Polymeric micelles represent nowadays an interesting formulative approach for ocular drug delivery, as they act as solubility enhancers of poorly soluble drugs and promote drug transport across cornea and sclera. In particular, in the last 5 years polymeric nanomicelles have been increasingly investigated to overcome some of the important challenges of the topical treatment of ocular diseases.

Areas covered

The aim of this review was to gather up-to-date information on the different roles that polymeric micelles (commonly in the nanosize scale) can play in ocular delivery. Thus, after a general description of ocular barriers and micelles features, the attention is focused on those properties that are relevant for ophthalmic application. Finally, their efficacy in improving the ocular delivery of different classes of therapeutics (anti-inflammatory, immunosuppressant, antiglaucoma, antifungal, and antiviral drugs) are reported.

Expert opinion

Although still a few, in vivo experiments have clearly demonstrated the capability of polymeric nanomicelles to overcome a variety of hurdles associated to ocular therapy, notably increasing drug bioavailability. However, there are still some very important issues to be solved, such as tolerability and stability; additionally, the role of micelles in drug uptake by the ocular tissues and their potential for the treatment of posterior eye diseases still need to be clarified/verified.

KEYWORDS:

• Nanomicelles
• nanotechnology
• ocular drug delivery
• eye diseases
• anti-inflammatory
• drugs
• cyclosporine
• anti-glaucoma drugs
• antifungal drugs
• antiviral drugs
• antioxidants

Article highlights

• The numerous challenges associated with topical ocular treatments require the design of advanced formulations, in which polymeric micelles can play a relevant role for their ability to achieve therapeutic drug levels in different ocular tissues.

• In ocular micelles, the surface-active molecules used are in most cases polymeric non-ionic surfactants.

• The absence of lipophilic excipients, the ability to increase drug solubility and stability, and to improve retention on the ocular surface together with the enhanced permeability across ocular barriers are remarkable advantages of polymeric micelles.

• Drug penetration inside ocular tissues is facilitated by the concurrence of increased drug solubility, permeation enhancing properties of unimers and uptake of intact polymeric micelles.

• Polymeric nanomicelles formulations withstand different sterilization methods and can be stored as freeze-dried solids that recover the original structure after reconstitution.

• Recently, the FDA approved the first nanomicellar formulation for ocular application of cyclosporine.

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.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was supported by Spanish MINECO [SAF2017-83118-R], Agencia Estatal de Investigación (AEI) and FEDER.