Abstract
Purpose :
Nitric oxide (NO) has recognized potential in preventing progression of glaucoma by lowering intraocular pressure, as well as corneal wound healing and sterilization. However, NO therapeutics are limited by rapid NO depletion, low concentrations, and narrow applicability due to drug coupling (unstable NO linked to a partner drug). Our goals were to decouple NO from a drug, while increasing concentration and duration of NO release. To achieve this, we designed and assessed a plasma-chemical treated, chitosan-coated, micellar NO delivery system, PCCM-125.
Methods :
We synthesized an immediate release NO donor oil through plasma-chemical treatment.
PCCM-125 was created by combining this oil with a similarly treated surfactant to form micelles, subsequently coated with chitosan and genipin-crosslinked.
Controls included NO-free oil and untreated chitosan coated micelles.
NO release in synthetic tear fluid (STF) was monitored over 24 hours for the oil (100μL in 1 mL STF) and 48 hours for PCCM-125 (1 mL in 10 mL STF), utilizing diazotization and dimethylphenol colorimetric assays for nitrite and nitrate.
Results :
Oil in STF: Immediately, nitrate in STF reached 255±12 mg/L, with nitrite of 45± 4 mg/L, and no significant change over 24 hours. Controls remained at 0.
PCCM-125 in STF: Undetectable nitrite levels in STF at 0 and 1 hour. 3 hours saw trace (0.07 ± 0.14 mg/L), increasing to 0.205 ± 0.065 mg/L at 6 hours. Peak at 12 hours of 0.28 ± 0.06 mg/L remaining relatively stable through 36 hours (0.24 ± 0.06 mg/L). Mild decline from 48 hours (0.225 ± 0.065 mg/L) to 0.185 ± 0.055 mg/L at 60hr.
PCCM-125 in STF showed a near linear increase in nitrate over 48 hours followed by plateau. Levels rose from undetectable to 2.4 ± 0.6 mg/L at 3 hours, steadily to 64 ± 5.7 mg/L at 48 hours, with plateau after. Controls in STF remained 0.
Conclusions :
PCCM-125 markedly enhances NO delivery in ophthalmology, showcasing a sustained release profile in STF, evidenced by a steady nitrite level and a gradual nitrate increase over 48 hours. This starkly contrasts with the rapid NO release observed with direct oil-STF mixing. By shifting from drug-coupled NO donors to a delivery-system approach, PCCM-125 overcomes the challenges of low concentration and rapid depletion. Thus, the PCCM-125 delivery-system likely has significant potential in glaucoma and corneal applications in future eye models
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.