Binding to Ocular Albumin as a Half-Life Extension Principle for Intravitreally Injected Drugs: Evidence from...

Area of Science:

• Ophthalmology
• Pharmacokinetics
• Drug Delivery

Background:

• The ocular half-life of intravitreally (IVT) injected drugs is critical for chronic intraocular treatment efficacy and dosing frequency.
• Extending drug half-life can significantly reduce the required frequency of IVT injections.

Purpose of the Study:

• To investigate the ocular pharmacokinetics (PK) of the Nanobody BI-X following IVT injection.
• To determine if noncovalent binding to vitreous albumin can enhance the ocular half-life of BI-X.

Main Methods:

• Wistar rats and New Zealand White rabbits received IVT injections of BI-X, with and without human serum albumin (HSA).
• Ocular exposure was assessed using whole eye homogenates (rats) and by measuring BI-X concentrations in aqueous humor, vitreous humor, and plasma (rabbits).
• Pharmacokinetic parameters were calculated to evaluate the effect of albumin coadministration.

Main Results:

• In rats, coadministration with HSA increased ocular BI-X concentrations 10-fold at 24 hours and 3-fold at 72 hours.
• In rabbits, coadministration with HSA resulted in an approximate 3-fold increase in vitreous half-life and a 5-fold increase in vitreous exposure.

Conclusions:

• The presence of albumin in the vitreous humor, even in healthy eyes and increased in disease states, supports albumin binding as a viable strategy.
• High-affinity binding to albumin presents a promising approach for extending the half-life of IVT injected drugs.
• This strategy could lead to less frequent dosing intervals for intraocular therapies.