Researchers led by a team from Virginia Commonwealth University (VCU) have developed a nanoparticle formulation for sustained-release drug delivery to prevent corneal graft rejection following corneal transplant surgery.
Give me some background first.
With corneal disease affecting over 4 million people worldwide, corneal transplantation is typically one of the last treatment options for vision rehabilitation and ocular tissue preservation. However, immunological rejection occurs in up to 50% of corneal transplant recipients and is the most common cause of graft failure.
Current immunosuppression therapy calls for topical corticosteroids delivered via eye drops, but the required dosage frequency—up to five times per day for a month with gradual tapering to potential maintenance dosing—often results in poor patient compliance as well as the increased chance of corticosteroid side effects.
Dexamethasone sodium phosphate (DSP), a corticosteroid, is commonly administered immediately after corneal transplant surgery via subconjunctival injection, but tends to washout rather quickly for long-term post-operative support.
What about these nanoparticles?
The research group initially developed poly(lactic-co-glycolic acid) (PLGA)–based DSP-loaded nanoparticles (PLGA DSP-NP) that resulted in sustained release of DSP over two weeks, but required weekly subconjunctival injection (which the researchers identified as clinically impractical in the long term).
This new paper covers the development of DSP-NP that uses custom-synthesized dicarboxyl-terminated PLA polymers (PLA-2COOH) to extend the duration of the sustained release in rat eyes.
So what did they find?
Over a period of 6 months, they found that the initial injection of PLA DSP-NP resulted in a high concentration of DSP in the anterior segment of rates' eyes as well as successful corneal graft survival, regardless of dosage.
Anything else?
The VCU researchers reported no significant intraocular pressure (IOP) increase at any dosage level over 6 months as well as a lower impact on body weight than that caused by a repeated corticosteroid eye drop regimen.
What’s next?
The researchers noted that the rats in the study still showed low levels of choroidal neovascularization (CNV), suggesting that this form of treatment might require concurrent anti-angiogenic treatment.
Furthermore, the size difference between rat and human eyes calls for further investigations on larger animals to determine risk level for ocular disease processes such as CNV.
Takeaway.
The new PLA DSP-NP offers a promising avenue for clinical research and development to continue to explore this potential new drug delivery platform.