Injectable in-situ gel depot system for targeted delivery of biologics to the retina

Abstract

In current clinical settings, frequent intravitreal (IVT) injections of anti-vascular endothelial growth factors are used due to their short in-vivo half-life and rapid clearance from the back of the eye. The IVT injections are associated with pain, risk of infection, retinal detachment, and financial burden. Biologics molecules can undergo physical, chemical, and enzymatic degradation during formulation development and in the biological environment. Moreover, the complex ocular structures also act as a rate-limiting barrier for these biologics. Thus, delivering stable and clinically relevant biologics concentration to the back of the eye is still a challenge. Compare to other drug delivery platforms, injectable in-situ gelling depot systems (IISGDs) have emerged as an effective system for biologics delivery. In this review, we have discussed various biologics used in ocular therapeutics and their associated challenges. Different routes of delivery and associated tissue barriers are also discussed. Different types of IISGDs developed to date for biologics delivery to the back of the eye were also covered. To conclude, various critical parameters related to the formulation development process and injectable depot systems that need careful consideration and further investigations were highlighted.

Keywords:

• Biologics
• ocular delivery
• ocular barriers
• protein
• peptides
• biopharmaceuticals
• in-situ gels
• injectable hydrogel
• anti-VEGFs

Acknowledgement

Authors would like to thank the Department of Biotechnology (DBT), DBT-RA Program in Biotechnology and Life Sciences, Government of India, for providing Research Associate Fellowship to Dr. Rohit Bisht. We would also like to thank the Indian Council of Medical Research (ICMR), Government of India, for providing grant support (2020-2882) to Dr. Jayabalan Nirmal.

Disclosure statement

No potential conflict of interest was reported by the author(s). The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Additional information

Funding

This work was supported by Research associate fellowship, Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India; grant support [2020–2882] provided by the Indian Council of Medical Research (ICMR), Government of India.