Light-responsive in situ forming injectable implants for effective drug delivery to the posterior segment of the eye

ABSTRACT

Introduction: Frequent intravitreal injections are currently the preferred treatment method for diseases affecting the posterior segment of the eye. However, these repeated injections have been associated with pain, risk of infection, hemorrhages, retinal detachment and high treatment costs. To overcome these limitations, light-responsive in situ forming injectable implants (ISFIs) may emerge as novel systems providing site-specific controlled drug delivery to the retinal tissues with great accuracy, safety, minimal invasiveness and high cost efficiency.

Area covered: Complex ocular barriers, routes for drug delivery, types of injectable implants, ocular application of light and benefits of light-responsive systems are discussed with regards to challenges and strategies employed for effective drug delivery to the posterior segment of the eye. In particular, we have highlighted photoresponsive moieties, photopolymerization mechanisms and different development strategies with their limitations as well as recent advancements in the field.

Expert opinion: Biodegradable light-responsive ISFIs are promising drug delivery systems that have shown a high degree of biocompatibility with sustained drug release in a number of applications. However, their use in intravitreal drug delivery is still in the very early stages. Issues related to the biocompatibility of the photoinitiator and the elimination of photo-degraded by-products from the ocular tissues need careful consideration, not only from a chemistry standpoint, but also from a biological perspective to improve the suitability of these systems for clinical applications.

KEYWORDS:

• Injectable implants
• light-responsive systems
• ocular drug delivery
• photocleavage
• photodimerization
• photoisomerization

Article highlights

• Conventional eye drops are unable to deliver the drug into the posterior segment of the eye due to the presence of complex barriers and elimination mechanisms, resulting in low ocular bioavailability.

• At present, frequent intravitreal injections are the preferred method for the treatment of posterior segment diseases which have been associated with pain, high risk of infection, hemorrhages, retinal detachment, and high treatment costs.

• The transparent nature of the cornea makes light-responsive drug delivery systems suitable for the treatment of ocular disorders offering various benefits, such as ease of application, site-specific controllability as well as instant delivery with great accuracy and safety.

• Light as external stimulus results in rapid sol–gel transition, high crosslinking density as well as improved mechanical strength of the resulting system.

• Biodegradable light-responsive injectable in situ forming implants eliminate the need for surgical removal after release of the payload and may be able to maintain the required therapeutic concentration for months.

• Selection of photoresponsive moieties (chromophores) and elimination of photo-degraded by-products from the ocular tissues need careful consideration.

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Declaration of interest

R Bisht is supported by a University of Auckland Doctoral Scholarship and work related to this article is funded by the Health Research Council of New Zealand. 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.