Controlled Release of Acyclovir Through Bioengineered Corneal Implants with Silica Nanoparticle Carriers

ABSTRACT

Herpes simplex virus (HSV) infection is the most common cause of corneal blindness in the Western world. Despite effective anti-viral drugs such as acyclovir (ACV), disease recurrence due to the virus establishing latency within the corneal nerves and possibly cells makes treatment very challenging. Furthermore, although effective, current systemic and topical preparations of anti-viral drugs do not appear to deliver sufficient quantities to the cornea to prevent reactivation. Current treatment for HSV vision loss is transplantation with donor corneas, but the surgery itself can reactivate viruses. We examined the feasibility of preventing viral reactivation during surgery, by sustained delivery of ACV introduced during corneal transplantation surgery, through encapsulation of the drug within silica (SiO2) nanoparticles (NP) incorporated into biosynthetic alternatives to donor corneas. We show that incorporation of NPs did not affect optical clarity of the collagen-based corneal substitutes nor their biocompatibility. NP-encapsulation effectively sustained ACV release from the biosynthetic implants over 10 days, compared to free ACV incorporated directly into the hydrogel constructs. The NP-enabled sustained release resulted in effective prevention of virally-induced cell death, not observed with the free drug. This early model demonstrates the feasibility of using biomimetic corneal substitutes that incorporate a drug release system (e.g. silica nanoparticles encapsulating ACV) as future alternatives to human donor tissue grafts, for transplantation of HSV-infected corneas.

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