Novel drug delivery methods for the treatment of keratitis: moving away from surgical intervention

ABSTRACT

Introduction: Corneal ulceration is one of the leading causes of blindness especially in low- and mid-income countries (LMICs). Surgical treatment of microbial keratitis is associated with multiple challenges that include non-availability of donor corneal tissues, lack of trained corneal surgeons, and poor compliance to follow up care. As a result, the surgery fails in 70–90% cases. Therefore, improving outcome of medical treatment and thereby avoiding the need for the surgery is an unmet need in the care of corneal ulcer cases.

Areas covered: In this review article, the authors have tried to compile information on the novel drug-delivery systems that have potential to enhance success of medical management. We have discussed the following systems: cyclodextrins, gel formulations, colloidal system, nanoformulations, drug-eluting contact lens, microneedle patch, and ocular inserts.

Expert opinion: The goals of corneal ulcer treatment are as follows: rapid eradication of causative microorganisms, control of damage from induced inflammation and microbial toxins, and facilitation of repair. The ocular surface anatomy poses several challenges for drug delivery using standard topical therapy. The novel drug-delivery systems mentioned above aim to enhanced tear solubility; superior stability; improved bio-availability; reduced toxicity; besides facilitating targeted drug delivery and convenience of administration.

KEYWORDS:

• Corneal ulcer
• cyclodextrins
• gel formulation
• colloidal system
• nanoformulations
• drug-eluting contact lens
• microneedle patch
• ocular inserts

Article highlights

• Corneal ulcer is a sightthreatening disorder. While excision of the diseased cornea and replacing it with healthy donor cornea is an option it is associated several shortcomings. Therefore, cure from medical treatment is desirable. Therefore, there is need for innovations to improve cure rate of medical management.

• Three key areas of improvement are: solubility in aqueous medium while preserving lipophilicity, retention on ocular surface; penetration through surface epithelium thereby increasing bio-availability; toxicity; and stability.

• Cyclodextrin-based formulations; gels, colloidal systems and nanoformulations all aim to achieve some or all of these improvements. Combining Xanthan Gum, HP-∣ ∣-CD, BAK and EDTA with voriconazole results in a significantly increased precorneal residence time and improved antifungal activity.

• External micro devices such as drug eluting contact lenses, microneedle patch and ocular inserts typically deliver accurate drug doses the at target site and over a longer period of time.

This box summarizes key points contained in the article.

Declaration of interest

P Garg receives funding for his research from the Department of Biotechnology, Government of India; Indian Council of Medical Research, India; and Medical Research Council, UK. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.