Recent advances in nanocrystal-based technologies applied for ocular drug delivery

ABSTRACT

Introduction

The intricate physiological barriers of the eye and the limited volume of eye drops impede efficient delivery of poorly water-soluble drugs. In the last decade, nanocrystals have emerged as versatile drug delivery systems in various administration routes from bench to bedside. The unique superiorities of nanocrystals, mainly embodied in high drug-loading capacity, good mucosal adhesion and penetration, and greatly improved drug solubility, reveal a promising prospect for ocular delivery of poorly water-soluble drugs.

Areas covered

This article focuses on the ophthalmic nanocrystal technologies and products that are in the literature, clinical trials, and even on the market. The recent research progress in the preparation, ocular application, and absorption of nanocrystals are highlighted, and the pros and cons of nanocrystals in overcoming the physiological barriers of the eye are also summarized.

Expert opinion

Nanocrystals have demonstrated success as glucocorticoid eye drops in the treatment of anterior segment diseases. However, the thermodynamic stability of nanocrystals remains the major challenge in product development. New technologies for efficiently optimizing stabilizers and sterilization processes are still expected. Strategies to confer more diverse functions via surface modification are also worth exploration to improve the potential of nanocrystals in delivering poorly water-soluble drugs to posterior segment of the eye.

KEYWORDS:

• Nanocrystal
• nanosuspension
• ophthalmology
• ocular drug delivery
• poorly water-soluble drug

Article highlights

• The intricate physiological barriers of the eye and the limited administration volume of eye drops make it challenging for poorly water-soluble drugs to achieve a high enough dose and delivery efficiency to meet the therapeutic needs of eye diseases.

• Drug nanocrystals have emerged as potential ocular drug delivery systems with enhanced bioavailability, extended drug release, improved safety and compliance, and feasibility of industrial production.

• Various poorly water-soluble drugs have been formulated as nanocrystals for the treatment of ocular diseases, among them, three glucocorticoid nanocrystal eye drops are now available in the clinic.

• Hybrid nanocrystals with environment-responsive fluorescent probes have deepened the understanding of the in vivo fate of ocularly applied nanocrystals.

• Several strategies such as prodrug, cationization, surface modification with penetration-enhancing biomaterials, or combination with mucoadhesive polymer solutions have increased the absorption of drug nanocrystals in the eye.

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 work was supported by the National Natural Science Fund of China [82273864], the Shanghai Science and Technology Program [21ZR1407100 and 21S11905300], and the Development Project of Shanghai Peak Disciplines-Integrative Medicine [20180101].