Safety, efficacy and delivery of multiple nucleoside analogs via drug encapsulated carbon (DECON) based sustained drug release platform.

Abstract

Purpose : Herpes simplex virus type-1 (HSV-1) is the leading cause of infectious blindness in the developed world. The current established method of treatment via nucleoside analog acyclovir (ACV) shows significant and effective viral suppression. Trifluridine needs to be administered up to 9 times daily to ensure effective ocular retention of the drug. We have previously uncovered use of drug-encapsulated carbon (DECON) as a sustained drug delivery platform. We have also yet to elucidate the drug loading and release profile and deduce the toxicity of the platform when translated to a living model.

Methods : Activated carbon was pre-weighed and UV sterilized overnight prior to making a 10 mg/mL sterile stock solution in PBS. ACV, PCV, GCV and FCV stock solutions were prepared in DMSO. Drug loading studies were performed in triplicate to assess the deviation between replicates. These samples were analyzed using Mass spectrometry, NMR. ACV loaded carbons were dropped on murine eyes for a period of 4 weeks, once everyday. Murine eyes treated with ACV, carbon, ACV loaded carbon or mock samples were evaluated every week for any signs of toxicity.

Results : In this study, we have evaluated the ability of activated carbon particles to load and sustainably release ACV and 3 other nucleoside analogues using MS. The carbon particles loaded with the drug, termed as DECON were also able to show excellent antiviral activity even when dosed therapeutically at 0.025 mg/mL. Furthermore, we showed that sustained administration of 0.1 mg/mL DECON particles to the eyes and vaginal tissue is very well tolerated and does not cause any unforeseen toxicity. In this regard, we conclude that DECON is a safe, efficacious and cost effective addition to the list of agents for topical delivery of antiviral agents to the ocular tissue.

Conclusions : Carbon-based technologies show promise in the area of targeted drug release in response to certain stimuli. Further research into the ability of DECON's ability to permeate beyond the cornea for release into other ocular tissues may reveal it’s ability to treat pathogens that travel beyond the routes taken by HSV-1 infection.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 3. DECON treatment does not significantly impact corneal dryness. Over 4 weeks, DECON, HPAC, ACV, and PBS (mock) were administered 3 times a day. NaOH was introduced during week 4 to a separate group of mice as a control.